December 14, 2023 PAO-12-23-RT-01
In 2023, the FDA released the draft guidance titled: “Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products.” This draft guidance provides insight into the FDA’s expectations for cell and gene therapy (CGT) developers regarding manufacturing changes and comparability assessments under chemistry, manufacturing, and control (CMC) requirements. Though the FDA has previously released similar guidance for other product classifications, CMC guidance specific to CGTs has been highly anticipated given the challenging, varied, and highly complex nature of the manufacturing processes associated with CGT development. For example, critical quality attributes (CQAs) have been difficult to establish for CGTs, particularly for products with multifaceted mechanisms of action, which may be difficult to reduce to a single or even several well-validated analytical readouts.
In the draft guidance, the FDA includes recommendations to assist sponsors in assessing impacts of manufacturing changes to investigational or licensed CGT products using tools such as risk assessments and comparability studies. Though such impact assessments have long been an FDA expectation (and more broadly an expectation for health authorities globally), the specific recommendations in the FDA’s draft guidance outlines that sponsors may need to submit a novel Investigational New Drug Application (IND) if they cannot demonstrate product comparability pre- and post-manufacturing changes from a quality, safety, and efficacy perspective.
As no developer can foresee all future changes to manufacturing procedures throughout the life cycle of a CGT product, this guidance, if implemented, raises the bar for how CGT developers assess risk from the outset of product design and manufacturing process development. While ultimately this guidance is subject to change prior to entry into force, developers should heed its recommendations carefully, ensuring phase-appropriate controls as they move through development and engaging the FDA to ensure alignment prior to implementation of manufacturing changes to their programs.
While it’s difficult to write about a single most consequential event or result in the pharma/biopharma industry in 2023, since a lot has happened and it continues to evolve, some notable topics are as follows:
2023 saw a downward shift and right-sizing of the biologics clinical pipeline. This led to reduced biologics clinical manufacturing capacity utilization, resulting in several CDMOs downsizing their assets. This trend was driven by the limited availability of biotech and biopharma funding, reduction in demand for infectious diseases management and expectations in managing the cost of goods. Limited funding means biotech and biopharma companies must often rely on established CDMOs with flexible offerings spanning the entire life cycle of their products. Moreover, regulatory expertise, quality, and the ability to de-risk development and manufacturing are key to securing funding. Getting the data package ready for an Investigational New Drug Application (IND) also represents a pivotal moment triggering a key funding milestone or a decision point, underscoring the importance of speed when advancing molecules through these regulatory milestones.
Simultaneously, 2023 brought an increase in regulatory approvals for a wide range of therapies, hinting at market stabilization and biotech funding returning to historical levels in the near future. On the other hand, the demand for large-scale biologics manufacturing was very strong as companies de-risked their supply chain and looked for cost-effective and reliable solutions.
The rising global spotlight on upgraded obesity drugs may be one of the most noteworthy events highlighting the biopharmaceutical industry in 2023. As clinical reports that demonstrated the improved therapeutic effects of obesity drugs, such as semaglutide by Novo Nordisk, started gaining attention within the healthcare industry in late 2022, the demands for weight-loss drugs have skyrocketed throughout 2023. The escalating need for obesity drugs globally made it challenging for drug manufacturers to supply enough amount of these advanced therapeutics to patients suffering from obesity –– a core risk factor of various cardiovascular diseases and diabetes.
Following semaglutide’s success, other large-scale drug makers, such as Eli Lilly, also placed their obesity drugs at the forefront of their sales activity. The amount of obesity-drug sales mirrors the rising global spotlight. Not only did Novo Nordisk become the most valuable company in Europe because of the rising popularity of its semaglutide in September, but also Eli Lilly’s tirzepatide, a rival drug to semaglutide, recorded approximately $3 billion in sales in nine months. Tirzepatide recording $3 billion in sales may manifest how much of the impact the emergence of obesity drugs has brought to the industry and will continue to impact in the future.
Lastly, if the global demands for weight-loss drugs continue to remain high in 2024 and beyond, there could be a scenario in which drug makers may have to collaborate with contract development and manufacturing organizations (CDMOs) that can help drug makers with supplying high volumes of obesity drugs to patients on time without any quality issue.
Limited availability of existing raw materials with the increased lead times
In a recent study published in Nature, scientists hailed the “Dusseldorf patient” as becoming “at least” the third person to have successfully cleared HIV without antiretroviral therapy (ART). The milestone was yet another proof of concept that replacing the entire immune system with stem cells from a donor with the rare gene mutation –– CCR5 –– that blocks HIV from entering cells could be a functional cure. This latest example of successful stem cell transplant builds on others seen with the “Berlin patient,” “London patient,” “New York patient,” and “City of Hope patient;” however, it exposed the inherent dangers, extended recovery times, and impracticality of finding rare HIV-resistant donors who are a match, making it unsuitable for widespread use.
The ability to manage living with HIV was a huge breakthrough — but it’s not enough. Despite the progress with ARTs, poor adherence and treatment failure are still a challenge. To address this, companies are taking different approaches leveraging the proof of concept to find a cure for HIV, such as cell and gene therapy. At Addimmune, we’re genetically enhancing HIV-specific CD4 T cells with the goal of strengthening the patient’s immune system. By harnessing the power of T cell immunity with unprecedented specificity, we have the potential to liberate people living with HIV from the burden of lifelong treatments.
Examples such as the Dusseldorf patient continue to shift the narrative around HIV treatment and point us toward a future where a cure is not only possible but also practical.
There were many significant policies and regulations in 2023, the Inflation Reduction Act (IRA) being one of the policies with the most influential updates with the significant changes related to government price controls on prescription drugs. It is imperative to think about how to create a market that rewards innovation in the biopharma industry, as well as noting how we can adjust capabilities and solutions in light of IRA
Generative AI adoption. In 2023, the pharma/biopharma industry witnessed a transformative event with the widespread adoption and integration of generative AI (GAI). This technological breakthrough is a game-changer, revolutionizing various aspects of the industry, from drug development to operational efficiencies. The implementation of GAI in pharma/biopharma is accelerating drug research and development, significantly reducing timelines, and transforming the way treatments are developed. Its ability to process and analyze vast data sets and generate novel insights has made it an indispensable tool in the industry. One of the most impactful applications of GAI is in drug molecular design, where it is streamlining early-stage drug discovery, resulting in significant reduction in development time and quicker progression to clinical trials. In clinical development, GAI automates and improves the design of clinical trials and medical-document generation favorably impacting project timelines. Manufacturing quality management is also benefiting from GAI with enhanced analysis and report generation boosting productivity. The integration of generative AI in pharma/biopharma in 2023 stands as a landmark event, marking a significant leap in the sector's evolution towards greater efficiency, productivity, and effectiveness.
A consequential event in 2023 was the publication of data in the New England Journal of Medicine validating PD-1 checkpoint agonists with game-changing outcomes, over six months, that were equivalent in both biologic-naive and biologic-experienced patients living with rheumatoid arthritis (RA). This suggests that specifically targeted activated immune cells may drive broad immunological outcomes to reduce inflammation and restore immune balance. In 2024, multiple phase IIb data readouts, including PD-1 agonists in RA and BTLA agonists in atopic dermatitis, may demonstrate their ability to break through the long-standing efficacy ceiling to raise the standard of care for the millions of patients living with these systemic, heterogeneous diseases.
In 2023, cell and gene therapy (CGT) experienced a paradigm shift with six new approvals by the end of Q2 (according to ASGCT) covering gene, cell and RNA therapy areas, marking a commercial breakthrough following the five approvals in 2022. This surge in clinical development reversed a decade-long downward trend, indicating the technical and commercial viability of CGT. The momentum fueled unprecedented dealmaking, signaling a promising era for the sector and patients.
Astrea Bioseparations is at the forefront, recognizing the need to democratize CGT therapies, by making them accessible to all, not just the privileged who can afford them. Our commitment is evident in our range of products featuring the AstreAdept® nanofiber technology, revolutionizing efficiency in CGT production. This innovative technology not only grants access to larger modalities but also compresses processes, outperforming outdated technologies. AstreAdept® reduces costs, saves time, and minimizes waste, aligning with our dedication to supporting CGT's success through efficient purification, thereby superseding old repurposed technology, which is highly inefficient.
Looking at the most consequential event in pharma/biopharma in 2023, the transformative evolution of CGT, marked by increased approvals, accessibility initiatives, and efficiency improvements, stands out as a milestone with far-reaching implications for the future of healthcare.
The field of regenerative and gene-editing medicines recently got a major boost with the first CRISPR treatment now approved, bringing a novel treatment to patients with transfusion-dependent beta thalassemia (TDT) and sickle cell disease (SCD). In November, the U.K. approved CRISPR-based therapy Casgevy exa-cel from Vertex Pharmaceuticals and CRISPR Therapeutics. In the United States at the time of this writing, we are now expecting the FDA’s affirmative decision on the treatment with a PDUFA date coming in a matter of days. This historic milestone is transformational for gene-editing therapies, as it gives stakeholders hope that this approach will revolutionize how we treat patients. With its impressive clinical data, the treatment heralds a new option to those battling these debilitating diseases.
It also validates the belief that there is a continued need for novel approaches that can get to the underlying mechanisms linked to genetic disorders. If we can tap into artificial intelligence (AI)-based approaches that can uncover the biology of nucleic acids, there is a possibility to create better targeted, precision medicines.
Within the space of RNA, there are several technologies aimed at developing RNA-targeted and RNA-based medicines, but none of these approaches can accurately and rapidly predict their 3D structures. If we know more about the actual structure of RNA molecules in the human body and how these molecules are structurally altered in disease, we can create safer, effective and more personalized medicines with fewer side effects.
I think the single most consequential event in the biopharma industry in 2023 is something that started prior to this year.
The ongoing macroeconomic conditions that have significantly reduced and/or delayed investment in pharmaceutical development and innovation have had a profound impact on our industry. While the economic conditions may begin to subside in the not-too-distant future, their impact is currently felt deeply almost everywhere in the industry. Many drug developers and innovators struggle to move their development further, or at a minimum, are facing significant delays in their progress. The stoppage and delays with the drug development programs then cascade to clinical trials, CDMOs, and related suppliers.
The bad news about this is obvious –– the resulting reduction in drug development programs and services in support of them. I believe there’s also some good news, although it may be less apparent from a surface view. With this significant reduction in investment and the resulting reduction in funding of drug development programs, all parts of the value chain have had to get smarter, sharper, and more efficient in order to survive and thrive. For example, drug developers requiring investment must generate more effective and market-viable products and business cases to earn the desired investments, and CDMOs must become more efficient and cost-effective with their services to earn the opportunity to work within the budgets of the drug developers they serve.
I believe that the drug developers and service providers who can survive and thrive through the current macroeconomic conditions will be big winners.
2023 is the year when CRISPR-Cas9 changes from being a gene-editing tool to being validated as a therapy. This bacterial immune system against invading viruses is now revolutionizing several areas of science, medical research, and agriculture. The technology relies on the programmable ability of the bacterial enzyme Cas9, guided by an RNA molecule, to cut and correct regions of DNA.
On October 16, NTLA-2001, an in vivo CRISPR-based gene-editing therapy, received FDA approval of an Investigational New Drug (IND) application to initiate a pivotal phase III trial for the treatment of transthyretin (ATTR) amyloidosis with cardiomyopathy. This therapy is designed to be a single, intravenous treatment that works in vivo, editing genes inside the human body rather than in cells taken from patients.
On November 16, the first ex vivo CRISPR/Cas9 gene-edited therapy, Casgevy, was approved by the UK MHRA for the treatment of sickle cell disease and transfusion-dependent beta-thalassemia. Patients' stem cells are "corrected" ex vivo using the CRISPR-Cas9 tool and infused back into the patient intravenously in a single dose. The therapy is also under review in the EU and U.S., where the FDA is expected to make an approval decision by December.
In 2023, the industry led the way to the first milestones in using the potential of CRISPR-based therapy to improve human health.
In 2023 we’ve seen the approval of weight loss drugs, which has had an impact not only on the population suffering from obesity, but also on society and the industry itself. Therapeutic peptides constitute the active pharmaceutical ingredient (API) of these types of drugs. They bind either the glucagon-like peptide-1 (GLP-1) or the gastric inhibitory polypeptide (GIP) receptors. They were originally developed to target type 2 diabetes and are also found to reduce body weight.
We are already starting to see an uptake in the use of nuclear magnetic resonance (NMR), which we believe will continue into the coming year, for the characterization and testing of this class of peptides. The size and structural properties of GLP-1 and GIP make them ideally suited to be studied by NMR, benefiting from the quantitative nature and wealth of structural information that accompanies the technique. This is underpinned by recent technological advances in NMR making it easier-to-use, more accessible, and affordable to both originator and generic companies.
When I think back on this past year, one of the most consequential events was the announcement by the U.S. Department of Health and Human Services, through the Centers for Medicare & Medicaid Services, of the initial list of Medicare Part D drugs that were selected for price negotiation under the Inflation Reduction Act (IRA). While the broader implementation of the IRA remains uncertain, especially as additional drugs from Medicare Part B are added to the list over time, it will likely impact the strategic research and development and capital investments within the biopharma sector. We will likely see more investment in cell and gene therapies (CGTs) that meet certain exclusion criteria under the IRA. Based on the current IRA criteria, all currently marketed cell and gene therapies are excluded. The exclusion of these therapies from the IRA will likely make CGTs more valuable and become a focal point for therapeutic developers within the biopharma sector to include them as part of their drug product portfolio. However, to realize this value proposition, you will need to see a manufacturing paradigm transformation within the CGT space that overcomes the current CMC pitfalls that continue to plague the industry. Therapeutic developers will need to focus on the incorporation of fully closed and automated platform technologies that allow them to reliably deliver safe, efficacious, high-quality, and cost-effective CGT drug products for all patients in need. We, at Cellares, are well-positioned to drive this transformation and accelerate access to these lifesaving cell therapies.
Many biotech and healthcare companies have suffered in the last months in terms of financing and stock performances, compared to the peak levels reached in the wake of the COVID-19 pandemic. This made the surge of Novo Nordisk’s market cap over the last three years tremendous.
In August 2023, this market cap overtook the Denmark’s yearly GDP, which should stand at $405.6 billion as forecasted for the year 2023, whereas Novo Nordisk’s market cap currently sits around $440 billion.
Thanks to its leading position as a diabetes drug manufacturer and a wave of demand for its highly effective diabetes and weight-loss drugs Ozempic and Wegovy, Novo Nordisk has for a while unseated LVMH as Europe’s most valuable company.
What’s more, the New York Times wrote at end of August 2023 that the company’s effect on the Danish economy is so large that Denmark has been able to keep interest rates lower than other European Union states, and that the national growth in the country has effectively relied only on the pharmaceutical sector since 2022.
While the weight loss drug market is expected to keep overperforming within the next decades, this major event in 2023 shows how significant the pharma sector has become and outlines how some countries can benefit from this sector, provided those countries are willing to support it and believe in its development.
The new FDA Draft Guidance on Prescription Drug Use-Related Software (PDURS) signals that the industry’s regulatory bodies are taking note of how software as medical devices (SaMD) can enhance pharmacotherapy outcomes. Combination products that combine drugs with SaMD-based therapy in a single prescription can boost efficacy in existing endpoints or extend efficacy to endpoints not currently targeted by the drug alone, resulting in improved outcomes for patients and a new product opportunity for pharma. Because the FDA has made clear the added benefit of software to drug labels, pharma will embrace opportunities to develop combination products that pair pharmacotherapy with SaMD. As a result, we will now start to see a race in the digitization of pharma pipelines.
There have been several advancements in our industry over the last year, particularly within the field of oncology, which has continued to produce diverse therapies in the hopes of targeting a broad spectrum of cancers. There have been multiple important oncology drug approvals, including Talvey for relapsed or refractory multiple myeloma and Fruzaqla for the treatment of refractory, metastatic colorectal cancer. There have also been multiple important data readouts this year as well. This includes the impressive results from the study of the CAR-T therapy, Carvykti, for multiple myeloma, as well as Roche’s phase III results for patients with ALK-positive early-stage lung cancer. These are all cancers that have significant unmet needs, and these therapies provide real hope for patients and their families.
At CoRegen, we’re always proud to see the ongoing innovation in our field and look forward to continuing to be a part of it. We’re focused on the cancer immunotherapy space and targeting the tumor microenvironment by leveraging the immune system’s inherent properties to fight a variety of aggressive cancers. CoRegen has identified SRC-3 as the gene responsible for serving as the lynchpin that provides significant protection to cancer cells. By knocking out SRC-3, which is overexpressed in most human cancers, the protection provided by Treg cells is removed, and the immune system’s ability to effectively identify and eradicate a broad array of cancers is activated. With strong preclinical data in hand, we look forward to moving our pipeline forward next year.
The marketing authorization approval of CASGEVYTM marked a historic milestone in the landscape of medicine, potentially ushering in a new era of targeted and personalized treatments. This achievement, a commercial therapy that leverages a CRISPR-Cas9 platform, signifies another progressive step beyond traditional pharmaceutical approaches toward the transformative power of genetic engineering in the realm of therapeutic interventions. Unlike conventional drugs that often treat symptoms rather than root causes, gene therapies can potentially directly target the underlying genetic factors responsible for diseases.
This approval represents a paradigm shift in how medicines are both made and imagined. The precision and specificity offered by CRISPR technology enable the industry to edit DNA with unprecedented accuracy, addressing genetic editing at the molecular level. This heralds a move toward treatments tailored to individual genetic profiles, potentially revolutionizing the way we approach a myriad of genetic disorders. The approval underscores not only the scientific and technological advancements achieved but also the collaborative efforts of researchers, clinicians, and regulatory bodies in navigating the complex ethical and safety considerations associated with gene editing.
As CRISPR-based therapies move from research and experimental stages to commercial viability, the life science community should anticipate a cascade of innovations and therapeutic breakthroughs. This approval represents another evolution in paving the way for a future where previously incurable genetic diseases may become manageable or even curable, offering renewed hope for patients and reshaping our understanding of what is possible in the field of medicine.
The single most important event for 2023 was the approval of anti-obesity drugs Ozempic and Wegovy, marking a significant turning point in healthcare for patients with obesity. Beyond the immediate impact on tackling obesity, the implications ripple across various facets of health and medicine.
The potential implications of wide adoption of this class of "mega medicines" are broad. First, these medicines stand to revolutionize the landscape of obesity treatment. With a presumed good safety profile and efficacy, their adoption could lead to a substantial reduction in obesity rates globally. This, in turn, could significantly alter the dynamics of several diseases and their outcomes. Obesity has long been recognized as a complicating factor in various health conditions, from infectious diseases like COVID-19 to chronic illnesses such as late-stage cancer. By addressing obesity, these drugs might potentially decrease the severity of such conditions, leading to improved patient outcomes and reducing the strain on healthcare systems worldwide.
All in all, the approval and widespread adoption of Ozempic and Wegovy represent a pivotal moment in healthcare. Their potential to mitigate obesity's adverse effects on various diseases could usher in a new era of improved patient outcomes, reduced healthcare burdens, and accelerated advancements in pharmaceutical innovation.
Generative AI (GenAI) was a disruptive turning point for AI advancement across all industries. It was a focal point for the pharma industry because it’s changing the way medicines are discovered, developed, and delivered. I’m excited about the potential opportunities for AI/ML in clinical trials and clinical development, many of which are being adopted by our clients as they look to scale, be more efficient, and arrive at answers to complex questions faster. I expect we'll see more exploration of large language models and use cases where AI can tap into unstructured data. The adoption and growth of ChatGPT is a clear example that this is not just buzz or hype. For pharma and biopharma, companies need to take AI seriously or risk getting left behind.
Advancement of AI/ML, even before the GenAI breakthrough of 2023, has been impacting drug discovery and accelerating drug candidates into preclinical and clinical trials. As AI advances pick up more speed in drug discovery, this will drive new and innovative approaches to clinical development, putting more pressure to be agile, fail fast, and be data-driven. In clinical development, where data volume has grown exponentially and macro conditions have placed a burden on drug development to be lean, cost-effective, and efficient, AI can help address some of these pain points. We are at an inflection point where tech and scientific innovation are driving a greater need for nimble, innovative approaches in clinical development, and AI has a role in the cause, effect, and solutions.
The COVID-19 pandemic has exposed the vulnerabilities of the global supply chain for pharmaceuticals and biopharmaceuticals, especially the reliance on outsourcing to low-cost regions, such as Asia.
Therefore, one of the most consequential events in pharma/biopharma in 2023 was the launch of the European Pharmaceutical Strategy, which aims to foster a more resilient, innovative, and competitive industry in the region. The strategy addresses some of the key challenges and opportunities that backsourcing production entails, such as ensuring access to essential medicines, promoting research and development, strengthening the regulatory framework, and enhancing collaboration among stakeholders. The strategy also supports the transition to a more sustainable and digitalized industry, which can help reduce environmental impact, improve efficiency, and enable personalized medicine.
This has prompted many companies to rethink their sourcing strategies and invest in building or expanding their own production facilities in Europe, where they can benefit from higher quality standards, regulatory alignment, and proximity to their markets. However, backsourcing production also poses some challenges for pharma and biopharma companies, such as higher capital and operational costs.
To succeed in this environment, companies need to continuously invest in smarter and more efficient production and quality capabilities. These capabilities are not easy to acquire or maintain, as they involve high upfront costs, sophisticated equipment, skilled personnel, and strict quality control. Consequently, the role of equipment and service suppliers has evolved to that of a partner, driving innovation, process improvements, and leveraging synergies.
Development of cancer vaccines over the past 50 years has been challenging and met with modest success. The tide is slowly changing as companies take innovative approaches to developing cancer vaccines that not only treat the cancer but prevent it from returning.
To eradicate cancer, we know we need to elicit strong T cell responses to recognize and kill the cancerous cells. As an industry, we have identified the antigens we need to immunize against some of the most aggressive cancers, and now have the technology including RNA, DNA, and our Amphiphile (AMP) platform, among others, for delivering the vaccines.
This year, we saw promising data from companies working with RNA and DNA cancer vaccines, in addition to preliminary data on Elicio’s lead cancer vaccine candidate, based on a lymph node–targeted AMP platform. What is particularly promising about these data from clinical studies is that we’re seeing more vaccines being given in the adjuvant setting, unlike before, and they are showing potential to clear up minimal residual disease and keep the cancer from recurring. The impact of these findings is informing a shift into exploring cancer vaccines in earlier-stage disease where the immune system is more effective and before resistance mechanisms develop. In this setting, it could potentially work as a prophylactic to prevent tumor recurrence.
I remain optimistic about the future of cancer vaccines as we advance our candidate, ELI-002, as an adjuvant monotherapy in patients with mKRAS-driven tumors into a randomized phase II trial in early 2024.
At Elixirgen Therapeutics, we work in a few different spaces, including rare disease and RNA-based therapeutics. We follow those fields closely and are excited by several key milestones/events.
Within rare disease, we were pleased to see several orphan drug approvals this year, including therapies for hemophilia, Friedrich’s ataxia, and Rett syndrome. These are rare diseases that patients and families have struggled with for a long time, so it’s been encouraging to see these approvals providing renewed hope for these communities. Our company is working on advancing a cell therapy for telomere biology disorders, which are caused by shortened telomeres. The leading cause of mortality is bone marrow failure, and currently there is no cure available except allogeneic HSC transplant. In 2024, we are looking forward to continuing work on our clinical trial, as well as seeing what advancements occur in rare diseases overall.
Within the RNA space, we were excited to see all the great technology advancements this year. This has been a rapidly growing field, and it’s been interesting to see how scientists have continued to build on the momentum established by the COVID-19 RNA vaccines. This year, we saw important data in the RNA cancer vaccine space for aggressive tumors like melanoma and pancreatic cancer, and we look forward to seeing how that develops. We’re working on advancing our c-srRNA (controllable self-replicating RNA) platform and published positive vaccine data this year. Next year, we plan to continue exploring further applications in infectious disease and cancer
The use of AI in target identification and novel compound generation was tremendously impactful over the last year, and we are now able to explore orders of magnitude more of the bioactive molecular space than previously possible with conventional drug discovery techniques. As such, an advancement I see in the coming year is the potential for technologies such as AI and machine learning to transform the course of translational research. My hope is to see models of translational research integrated with compound generation models to begin to generate not just novel compounds but compounds with a greater probability of efficacy and reduced off-target effects in people.
In the post-COVID era, pharma companies across the globe are realizing the long-term commercial growth plans they previously set need to be replotted against broader macroeconomic headwinds. This includes smaller pharmaceutical companies fighting to keep operations funded while continuing to move their pipeline of drugs through late-stage clinical trials and mid- and large-cap pharma companies resetting broader revenue and growth expectations amid rising inflation, which will continue to impact manufacturing, supply chain, and ultimately drug costs across the global market. The collision of inflation and broad-reaching regulatory changes is real, almost cataclysmic, as pharmaceutical and life science companies will need to take their once "recession-proof mindset" and pivot how they go to market in future years as the year 2023 becomes an economic baseline moving forward.
The boom in monoclonal antibody (mAb)-based therapies continued in 2023. As anticipated, more biosimilars hit the market as patents expired for key mAbs, such as Adalimumab, which is used to treat inflammation. This trend is expected to continue, as many new biosimilar projects were started at biologics companies targeting MAbs with patent expiry 2025–2028. Production cost plays a more prominent role for biosimilars, and the industry is looking for options to further increase productivity. Chemically defined cell culture ingredient–based solutions, like those offered by Evonik, continue to help biosimilar mAbs developers to optimize cell culture media platforms and work with cost-effective bioprocesses.
Another big development in the industry was the approval and launch of Leqembi by Biogen/Eisai to slow the progression of Alzheimer’s disease. This showed that there’s great progress being made with new indications for antibody therapies. However, for new indications with a large patient population, the industry must continue to work on manufacturing efficiency to supply enough product at a reasonable cost.
The pharmaceutical landscape witnessed a pivotal moment in 2023 with the reintroduction of the PASTEUR Act, marking a significant stride in the battle against antimicrobial resistance (AMR). Recognizing AMR as a pressing global health threat, the PASTEUR Act proposes a groundbreaking subscription-style payment model to stimulate antibiotic development and combat superbugs. By establishing contracts between the government and antimicrobial developers, the Act’s innovative approach ensures sustained access to novel treatments and addresses the financial challenges faced by pharmaceutical companies while simultaneously encouraging appropriate use of antimicrobials across the healthcare system.
The urgency of the AMR crisis, emphasized by organizations like the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), underscores the importance of the PASTEUR Act. Antibacterial-resistant infections caused approximately five million deaths globally in 2019 and, without intervention, superbugs are projected to claim 10 million lives annually by 2050. The act provides a much-needed incentive, fostering an environment where developers can focus on innovation without financial concerns. The PASTEUR Act levels the economic playing field for antimicrobial developers and instills confidence in the pharmaceutical industry. By supporting small biotech companies and motivating researchers to explore new drugs, the act paves the way for a revitalized antimicrobial ecosystem. The reintroduction of the PASTEUR Act offers a beacon of hope in the fight against antimicrobial resistance and signals a collective commitment to safeguarding public health worldwide.
A significant trend is the critical examination of GLP-1 (glucagon-like peptide-1 agonists) medications, which could be societally defining in the coming decades. The promise of eradicating or greatly slowing obesity in society is somewhat of a modern holy grail. However, there are no free lunches, and so despite the efficacy and manageable side effect profile of these drugs, we need to be cautious due to long-term side effects that might not be fully fleshed out in the highly managed clinical trial setting. Additionally, weight loss tends to bear econometric fruit in future years, and payers aren’t known for loving that equation when their members are on average retained for only two years. While the Zepbound masses might look and feel better in their Christmas sweaters, payers care most about the two-year cost savings.
The recent approval of CASGEVY in the UK is, like the approvals for mRNA vaccines during the COVID pandemic, a transformational event for our industry. More and more, new modalities are finding their way to clinical impact and product approvals. In spite of chilly market conditions, this should continue to build confidence in our industry as we demonstrate an ability to engineer biology with higher fidelity.
Earlier this year, the government began its first negotiations to limit the prices of certain drugs as part of the Inflation Reduction Act. While this is a complex change in regulatory policy that will have long-lasting implications for drug development, it highlights a more important issue related to ensuring drugs can reach patients.
While small molecules have been the mainstay of drug development for decades, biologics, specifically protein-based therapeutics, are becoming increasingly more common. The current process, which leverages cell culture systems, is incredibly complex and expensive to maintain. If we are to ever meet the growing demand, we need a better solution.
Plant-based manufacturing offers an incredibly promising avenue. From a cultivation standpoint, we’ve made incredible progress in adjacent industries that allow high-yield cultivation in a controlled and even automated environment. More importantly, while the starting material would be different from traditional cell culture, the downstream process would be identical and require little to no changes in existing infrastructure.
The historic challenge has been biology. Differences in protein production between mammalian and plant systems have hindered this transition. However, improvements in genetic engineering and a deeper understanding of plant biology have allowed us to make that critical leap to facilitate the production of candidates with promising safety profiles.
At KBio, we’re harnessing our plant-based biofoundaries to create protein-based therapeutic candidates quickly and at scale. We have already demonstrated early signs of efficacy with our candidates and importantly, a promising tolerability profile, which supports the future potential of our approach.
The event with the biggest impact on 2023 actually happened the year before, with the signing of the Inflation Reduction Act (IRA). It wasn’t solely responsible for the state of the biotech market –– we were already facing high inflation with rising capital costs, balancing high development costs with a challenging fundraising environment, and difficulties around finding the experienced staff needed to keep cell and gene therapies advancing. But it is emblematic of the headwinds we faced; 2023 has been the year where even the bravest of the biotech world may have experienced moments of hesitancy.
However, the most stoic have prevailed. And in the long run, it will make the industry stronger, as we will learn to optimize the resources we have and adapt to the new era of post-IRA pricing models and limited resources.
One key to moving forward is artificial intelligence (AI). We are at the tipping point of a biotech transformation, and in 2023 we embraced the first large-scale AI applications. Algorithms can help identify and validate potential drug targets by analyzing complex biological data sets to accelerate the early stages of drug discovery. AI can be used in the design and optimization of drug candidates. Machine learning can be leveraged to predict the biological activity and safety profile of potential drugs, helping researchers prioritize and optimize lead molecules. AI is also contributing to the development of personalized medicine by analyzing patient data, including genetic information, to tailor drug treatments based on individual characteristics.
The most pivotal development, in my opinion, centers around the remarkable impact of GLP1 or GIP agonists. Originating as a focused approach to diabetes therapeutics, their influence has transcended expectations, profoundly affecting both patients and humanity at large. What began as a targeted solution has evolved into a transformative force, extending well beyond the realm of diabetes management. This therapeutic breakthrough, akin to the revolutionary mRNA solutions for COVID, prompts us to ponder the future beyond 2022 or 2023.
This advancement not only addresses immediate medical needs but also reshapes our understanding of lifestyle management, presenting a broad and profound impact on human existence. The implications are far-reaching, echoing through the years and reaffirming the progress from a life expectancy of around 55 years in 1928 to over 80 years today. The prospect of living longer and enjoying a higher quality of life is a consequential event, underscoring the indispensable role of pharmaceuticals and healthcare in our evolving industry.
The increased interest in the integration of artificial intelligence (AI) into biopharma is arguably the most pivotal development of 2023. Since the onset of the COVID-19 pandemic, the biopharma sector has significantly ramped up its utilization of AI, and this trend is expected to continue as more breakthroughs emerge.
There is strong recognition within the biopharma industry that AI is a critical investment as the landscape of life sciences and biotechnology continues to evolve.
The success of AI in biopharma will be dependent on a company’s ability to apply these emerging tools in conjunction with technological tools and expert guidance. Similarly, success of AI integration hinges on the right inputs, which goes beyond digital assets and encompasses a dedicated team of experts adept at navigating AI-driven processes.
The potential for AI spans a multitude of clinical applications, offering reduced trial durations, lower costs, and decreased unnecessary drug exposure, among other benefits. Examples of applications within clinical development include substituting synthetic and external control arms for true control or placebo groups and using machine learning to model inclusion and exclusion criteria based on toxicity reports. Within clinical operations, AI can be utilized to identify the most suitable patients for a particular trial quickly and precisely and can even conduct basic pre-screening activities through the use of virtual assistants.
The strategic utilization of AI, enabled by an expert team like the one at Medicus Pharma, is a combination set to revolutionize clinical trials. The year 2023 marks a turning point, positioning AI as a cornerstone of biopharmaceutical innovation.
From its discovery in 2012, genome editing has emerged as a powerful tool for developing new cell therapies. With the ability to precisely modify genes, researchers can engineer cells with enhanced therapeutic properties or correct genetic defects that cause diseases. 2023 has proven to be a truly historic year for medicine, with the first CRISPR-based therapies entering regulatory review. The advancement of exagamglogene autotemcel (exa-cel), the world’s first CRISPR/Cas9-based medicine, to Biologics License Application (BLA) by Vertex and CRISPR Therapeutics once again proved that the discoveries of dedicated scientists ultimately make possible the development of new therapeutic modalities with life-altering potential for patients. With the approval by U.K. health authorities of exa-cel, now marketed under the name Casgevy, for sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) patients suffering with these life-threatening genetic diseases now have access to potentially curative treatment for the first time in history.
The approval of peptide therapeutics by regulatory agencies has grown steadily since the 1980s for a variety of uses, including hormones, anti-cancer, anti-viral/bacterial, anti-inflammatory, and diagnostic testing, to name a few. These therapeutics are unique due to their combination of low manufacturing costs, improved specificity of small molecules, and high efficacy with lower immunogenicity of protein-based biologics. However, the peptide bonds are easily hydrolyzed and rapidly degraded by the body, resulting in poor half-life. Administration of these drugs is primarily through intravenous (IV) routes, which often results in poor patient compliance and potential complications.
Efforts have been made to improve stability by linking portions of linear peptides to form cyclic structures that improve stability, permitting oral administration of drugs traditionally delivered by IV. Once the peptide is hydrolyzed at a site in the ring, the result is a linear-like peptide that is rapidly metabolized, so synthetic efforts to block these sites maintain their ring structure once identified. In 2023, a study found that cyclic peptides represent 46% of the total approvals by regulatory agencies, and that number is growing; however, identification of the soft spots where hydrolysis occurs remains an analytical challenge due to the formation of isomeric products when the ring structure is broken at a single point simultaneously. Methods such as high-resolution ion mobility coupled with mass spectrometry (HRIM-MS) can be employed to separate and identify these isomeric products.
Given all the advancements in the pharma space over the past year, it would be difficult to say a single event could be considered the most consequential. AI-enabled drug discovery was a very significant event that occurred this year. However, the use of AI and machine learning in drug discovery is still very much in the initial stages and is still growing. The benefits of this are expediting the drug delivery process, which allows the identification of novel drug candidates faster, more accurately, and efficiently. This advancement could lead to the development of breakthrough therapies for various diseases, which could significantly impact patient outcomes.
Certainly, the Inflation Reduction Act will continue to play out as it relates to pricing and reimbursements, as well as potential impacts to exclusivity. But putting aside regulatory impacts for a moment, the most consequential change I see is the democratization of AI. AI in and of itself has been put into practice by companies for years, but now there’s this ever-expanding canvas upon which to apply it. As a result, over the next few years, we will see an acceleration of AI-driven analytics and product development across the entire clinical and commercial ecosystem.
Pharma, like many industries, has been awash with data, but it’s been siloed. This data came from an array of sources –– public, private, third-party, one-off, syndicated, and/or derived from a mix of all. Data abundance isn’t the problem. But a lack of concrete answers with use-case relevant specificity comes up again and again in my discussions with clients. In other words, don’t just give me data, tell me how I should be thinking about it.
Just as when search engines first organized the internet, giving us access to the entirety of the world’s content, we can now take that content and decipher it faster and more accurately than ever before. That can mean augmenting proprietary data assets built over decades with unstructured content generated in real time to extrapolate a deeper context. It means taking a very complex display of information and, in natural language, explaining to a leader who doesn’t necessarily swim in that data every day. In practical terms, it means supporting a higher likelihood of success on the first attempt, such as in protocol designs or commercial performance forecasts.
The single most consequential event or result, in my view, has been the passage and implementation of the Inflation Reduction Act (IRA). This legislation brought about a profound and multifaceted impact on the industry, reshaping the operational and strategic frameworks within which we operate. The IRA's influence extends beyond immediate financial implications; it alters the dynamics of research and development, commercialization strategies, and go-to-market efforts. This legislative change has compelled companies to reassess their long-term plans, balancing innovation with the new economic realities imposed by the law. The IRA, therefore, stands not just as a regulatory milestone but as a catalyst for a significant shift in how the pharmaceutical industry approaches its core functions, from drug development to market delivery. Other challenges, like the growing demand for a specialized workforce, supply chain disruptions, the need for more diversity in clinical trials, and the rising threat of data breaches and cybersecurity risks, are undoubtedly critical. Each represents a significant hurdle in its own right, and collectively they contribute to an increasingly complex operational environment. However, the IRA's comprehensive impact on the industry's economic and strategic landscape positions it as the most consequential development of 2023. This law not only challenges us but also offers an opportunity to innovate and evolve. It urges us to rethink how we conduct research and approach market strategies and, ultimately, how we contribute to healthcare. The IRA's long-term implications on our industry are profound, marking 2023 as a pivotal year in the history of pharma and biopharma.
The omnipresent dynamic of 2023 has been the decline in COVID, with patients, providers, and the pharma/biopharma industry adjusting to the aftermath of the pandemic. COVID-related deaths continue to fall, currently reaching levels seen in the very early days of the pandemic and vaccines update has diminished alongside the decrease in threat. As a result, pharma companies that have focused on COVID vaccines are faced with a steep cliff and need to adjust accordingly.
Similarly, we all can attest to the permanent changes that have resulted in this historical episode. A collective shift from treatment to prevention. Patient journeys have changed with often longer times to diagnosis and treatment. Remote work and communication through digital means is here to stay and has altered the dynamic between patient and provider dramatically, while also removing barriers to access for many populations. The presentation of a clear need to rapidly stand up and execute clinical trials that are robust and inclusive. These shifts amplified even further in the context of ongoing efforts around targeted medicines, patient-centricity and representativeness and the need to get treatments/products to the right populations, quickly and safely in the real world setting.
Integrated evidence planning, underscored by the use of real-world data (RWD) and evidence (RWE), is key to moving through to the post-pandemic environment. With more constraints on funding and increasing challenges with market access, RWE can drive targeted approaches to populations where the product will be most effective and deliver the best outcomes. A thoughtful, integrated evidence-generation effort will support optimized development planning, efficient data collection efforts, and regulatory requirements and aid in engagement with providers and patient communities to demonstrate performance in the real world.
In 2023, we saw the first-ever regulatory approval of a gene-editing therapy, which is just the start of what could be a tsunami of entirely new classes of medicines that tackle diseases at the genetic level. Since its initial description in 2012, CRISPR technology has moved from a concept in academic labs to a broadly accepted technology fueling drug development to an approved treatment that will be available to patients. This moment represents much more than a new treatment. It speaks to the accelerating pace of technological evolution and the emergence of new therapeutic modalities within biotech. Even now, new approaches are on the horizon, aiming to surpass CRISPR and address the root cause of disease.
The emerging field of precision epigenomic modulation through programmable mRNA therapeutics is the next frontier of innovation with the potential to usher another watershed moment. Improvements in our understanding of genomic architecture, coupled with the accelerated rise in artificial intelligence and machine learning applications, have the potential to drive the evolution of this field even faster and advance this therapeutic modality with far and broad reach across disease pathologies. Groundbreaking research in 2016 shed light on the underlying biology behind epigenomic regulation, and we have rapidly and successfully advanced a new therapeutic class, called epigenomic controllers, from an idea through preclinical studies to clinical proof of concept. We are entering a new age, where medicines are not discovered but prospectively engineered to control the underlying biology of any disease with unparalleled precision.
The life sciences industry witnessed a major milestone with the approval of the first-ever CRISPR-based therapeutic in the UK, Vertex’s Casgevy. After just 11 years since the invention of the technology, this monumental decision opens up a major opportunity within biopharma for bringing gene-editing therapies to patients in need of historically hard-to-treat genetic disorders. With CRISPR and other advances, we can now dive deep into the underlying cause of these diseases and enable disease-modifying changes to hopefully improve outcomes for patients.
With advances like CRISPR and AI, there is now a fundamental shift in how many are approaching the drug discovery process. Scientists can harness the power of these advances by tapping into automation and robotics and significantly shorten conventional timelines, especially within the context of genomics and screening workflows. Automated processes help guarantee precision and accuracy, significantly diminishing both time and costs in comparison to conventional methods, leading to more cost-effective utilization of reagents and minimizing human-based errors. With easy-to-use AI-based tools like large language models and other open-source resources now becoming more accessible, we can break down the barriers to entry into automation for scientists worldwide.
If we can accelerate the adoption of automation, especially for newer modalities like CRISPR, we can significantly impact the scale and reach of research efforts, which will subsequently lead to safer, more effective therapies for patients.
The unprecedented wave of layoffs sweeping across the biopharmaceutical industry in 2023 has sent shockwaves through the sector. Driven by rocky market conditions, this surge is having the near-term effect of creating a dire talent shortage at innovative biotech companies that threatens to derail the development of the next wave of lifesaving drugs and therapies. The fallout from these layoffs poses a significant risk to the future of innovation and patient care, demanding urgent attention from industry leaders and policymakers.
This crisis of skilled workers is particularly concerning for an industry already grappling with a shortage of qualified professionals, making it increasingly difficult to conduct clinical trials, secure FDA approvals, and bring new medications to market. The staffing difficulties have been particularly acute in the cell and gene therapy space, where everyone in the value chain from therapeutics developers to regulators has had difficulty finding skilled workers to support the industry’s rapid growth.
As the adage goes, that may be the place for opportunity hidden in this crisis. As market conditions improve and investment returns at scale, there may be a larger pool of available scientists and other skilled staff willing to make the transition to advanced therapies. Perhaps it will be the push the space needs to capitalize on its promise, improving access to the cutting-edge therapies.
In my view, the single most consequential event in 2023 was the launch of biosimilars to HUMIRA (adalimumab) in the United States. Industry is now at a critical juncture with a massive opportunity to ramp up adoption of these medicines to help reduce the affordability burden of high-cost brand biologics on patients and on the health care system overall.
Although technically passed into law in 2022, the first drugs selected for price negotiations with Medicare as part of the Inflation Reduction Act were just announced in August of this year. The Inflation Reduction Act gives Medicare the ability to negotiate prices, and the industry is anxiously awaiting the results of these negotiations. CMS will announce the results of each negotiated price in September 2024. This legislation is aimed at lowering the cost of medications to 18.7% of the U.S. population that is on Medicare. The ripple effect in terms of drug development and manufacturing is yet to be fully felt. There is a fear that the development of lower-cost drug therapies may be abandoned in favor of higher-priced therapies as the industry looks to maximize profits while they can, and, in turn, essential medicines or new life-saving therapies may not ever make it to the marketplace.
In 2023, the cell and gene therapy (CGT) industry was hit hard. After years of significant investment, consistent failure by CGT companies to preserve capital while pursuing clinical inflection points soured investor appetite. The setback has instigated a pivotal paradigm shift in cell therapy manufacturing this year. To enhance the future viability of CGT companies, large-scale collaborative efforts between vendors and CGT companies have been undertaken to enable high-throughput and cost-effective CGT manufacturing.
By applying principles and methods successfully implemented to manufacture automobiles, medical devices, bottled water, and even cheeseburgers at McDonald's, CGT manufacturers are beginning to collaborate with their equipment and critical materials vendors to create simple, repeatable, and easily automated unit operations, using standardized reagents, standardized sterile connections, standardized equipment, standardized workflows, and standardized processes. These collaborations will create a revolution in the development of low-cost, scalable manufacturing processes, which will be crucial for quickly translating immense therapeutic potential from the lab to practical, widespread dissemination.
Central to this revolution has been the G-Rex integrated cell therapy manufacturing platform. By eliminating the need for continuous fluidic connection to capital equipment during incubation, the G-Rex enables cell therapy manufacturers to employ the high-throughput production principles and methods successfully employed in other industries.
Driven by this revolution, the industry experienced a surge in collaborative efforts among academia, industry, and regulatory bodies in 2023. This collective effort will improve manufacturing efficiency and accelerate clinical milestone timelines, thereby significantly reducing the costs and capital expenditures required to reach clinical milestones compared with the existing business model. Ultimately, this will expand access to these lifesaving treatments.
I believe the single most consequential event to affect the pharma market in 2023 has and continues to be the macroeconomic climate. Inflation has posed significant challenges for the pharmaceutical industry in 2023, impacting various aspects of drug development, manufacturing, and distribution. Rising input costs, including labor and transportation, have put pressure on pharmaceutical companies' profit margins, leading to increased scrutiny of drug pricing strategies with governments and payers seeking to contain healthcare costs.
Inflationary pressures have also disrupted supply chains, causing delays in drug deliveries and shortages of essential medications. These disruptions have exacerbated existing challenges in the pharmaceutical industry, such as complex global supply chains and regulatory hurdles. To mitigate inflationary pressure, pharmaceutical companies have implemented various cost-saving measures, including streamlining operations, negotiating better deals with suppliers, and exploring alternative manufacturing processes. Other options, such as launching new products, expanding into new markets, and pursuing strategic partnerships, have also been explored.
Despite these efforts, inflation is likely to continue to be a significant challenge for the pharmaceutical industry in the near term. Companies will need to adapt to this new reality by finding innovative ways to manage costs and improve efficiency while maintaining the quality and safety of their products.
Insulin has been the standard treatment for people living with diabetes since its discovery in the early 1920s. For patients, living with diabetes requires constant blood glucose monitoring, raises the risk of complications from other life-threatening diseases, and increases the required long-term investment in personal healthcare. By 2040, the global prevalence of type 1 diabetes (T1D) is predicted to grow to between 13.5 and 17.4 million people. After over 100 years of treating diabetes with insulin injections, the millions of people living with T1D need new treatment options. In 2023, the approval of the first cellular therapy to treat patients with T1D was a small step in the right direction.
Across the biopharma industry, there are several cell therapy–based treatments in development for diabetes. These potential treatments, including our novel cell therapy platform in development at Sernova, utilize a novel medical device for the long-term housing of therapeutic cells. Importantly, work is being done to create ethical and scalable sources of therapeutic cells, as opposed to donor cells. Of focus is the development of stem cell–based sources, which can be produced in commercial quantities. Several companies, including Sernova, are also developing immune-protection technologies with the goal of advancing past the need for intense immunosuppressive protocols. In early clinical evaluation, our Cell Pouch System™ has shown great potential as a “functional cure” for people living with diabetes by combining a novel medical device with therapeutic cells.
The pharma industry has faced significant challenges over the past few years, with the ongoing impact of war, rising energy prices, and supply chain pressures. In 2023, the escalating cost of raw materials significantly inflated supply chain expenses for drug manufacturers. Such cost escalations have driven organizations to reassess their supply chains, either to minimize expenses or ensure a consistent supply. These pressures have made it more important than ever for companies providing packaging for pharma manufacturers to innovate and meet customer needs with new products and solutions that enable them to bring their drugs to market quickly and safely.
The rising energy costs experienced in past years have also accelerated the pharma industry’s prioritization of decarbonization and other sustainable investments. Glass manufacturers are under pressure to bring forward their energy efficient investment, especially because glass manufacturing is energy intensive. Converting a gas furnace to electric is a huge investment, but it reduces energy consumption by reducing emissions rapidly.
The Science Based Targets initiative (SBTi) is a partnership between CDP, the United Nations Global Compact, World Resources Institute (WRI) and the World Wide Fund for Nature (WWF) enabling businesses to set ambitious targets for emissions reductions in line with leading climate science. Science-based targets show companies how much (and by when) they need to reduce their greenhouse gas (GHG) emissions to prevent the worst effects of climate change. With global bodies like the SBTi, companies across the world can accelerate their efforts to halve emissions before 2030.
While there were many significant pharma/biopharma events in 2023, including several M&A megadeals (Pfizer/Seagen, Biogen/Reata, and Merck/Prometheus), the Inflation Reduction Act and its impact on the pharma industry and a new focus on obesity medications, the resurgence of antibody–drug conjugates (ADCs) as oncology's hottest class is perhaps the most consequential.
Although they have been around since the early 2000s, the “smart bombs” in cancer therapy have experienced an explosion in popularity thanks to advancements in technology. Over the past decade, we've advanced from first- to third-generation ADCs, which now use specific small molecule drugs binding to antibodies, improving stability and drug release without extra harm.
Today, there are approximately 15 marketed ADC therapies approved for various indications, including leukemia, breast cancer, head and neck cancer, cervical cancer, and ovarian cancer. But with more than 100 ADCs in development, the impact of ADCs will reverberate beyond 2023 as they have the potential to reshape the landscape of cancer care. At the European Society of Medical Oncology (ESMO) Congress this past October, much of the focus was on ADCs, with one leading cancer researcher declaring, “this is the decade of ADCs.”
This resurgence of ADCs reflects a significant turning point in the industry, and we’ll see a proliferation of them in the future, resulting in improved ADC technology to treat a wider range of diseases –– and do so more safely.
Obesity has been catapulted into the limelight, both as a public health emergency and a highly lucrative therapeutic class, replacing COVID-19, which had held this place in 2020 and 2021.
Sales of Novo Nordic’s Wegovy, the first of a new generation of obesity treatments, have soared since its launch in the United States in June 2021. Eli Lilly’s Mounjaro was approved for weight loss in the United States in November of 2023, and sales of the product are projected to reach $14 billion by 2028 (Evaluate Pharma). Worldwide sales of obesity products are expected to reach over $29.4 billion by 2028 (Evaluate Pharma).
Demand for COVID-19 vaccines significantly declined in 2022. Sales of products related to SARS-Cov-2 topped $100 billion in 2022, which will come in at less than half of this in 2023, and are likely to drop to around $30 billion by 2028, according to current Evaluate Pharma projections.
These shifts in market dynamics have now created a capacity crunch for prefilled syringes (PFS) very similar to the capacity crunch many CMOs experienced for liquid vials back in 2020, creating an opportunity for companies to establish longer-term relationships with clients to secure capacity. This trend emphasizes the importance of strategic partnerships in navigating supply challenges and ensuring a stable and reliable source of sterile injectables.
Simtra BioPharma Solutions’ Bloomington, Indiana, plant is one of the largest PFS CDMOs in the world, with nearly 300M units produced over the past five years. We work very closely with our customers to ensure continuity of supply of the products that are manufactured at our facilities and engage in dialogue regarding any increase in future capacity needs in order to plan appropriately. As our clients' needs continue to grow and evolve, Simtra has a long-standing history of making continuous investments to our facilities.
In 2023, a significant trend in the pharma industry has been the increasing trend toward home delivery for products filled into syringes. This represents a shift in the healthcare landscape toward enabling patients to administer medications in the comfort of their homes, aligning with a broader trend toward empowering patients and enhancing the overall patient experience.
The primary innovation driving this change is the use of pre-filled syringes, which eliminate the need for patients to visit clinics for intravenous infusions by allowing them to self-administer prescribed drugs at home. Diabetics have self-administered insulin at home for years, demonstrating the feasibility of this patient-centric approach for broader-use cases. Pre-filled syringes and autoinjectors also offer additional convenience as patients no longer need to measure their dosages.
In preparation for increased use of at-home pre-filled syringes, drug developers are reformulating biologics to be more concentrated, minimizing the injection volume. This strategic adjustment to address logistical and technical challenges underscores the industry's commitment to optimizing the efficiency and practicality of home-based medical interventions.
A crucial aspect of the successful expansion and adoption of home delivery of medication that can be self-administered is the deepening trust and collaboration with CDMOs. As the demand for pre-filled syringes continues to grow, driven by advancements in technology, patient demand, and market preference, pharmaceutical companies are increasingly relying on CDMO partnerships for their specialized expertise in development and manufacturing.
In response, Thermo Fisher is expanding our capabilities to address customers’ manufacturing needs as applications grow beyond vaccines to biologics and biosimilars.
The initial approval for a new generation of cell and gene therapies (CGTs) for sickle cell disease (SCD) signals a ray of hope for those managing this debilitating disease. The monumental 2023 achievement highlights an unsung hero behind gene therapy developments: cell collections.
Cell collections are a critical step in a patient’s procedural journey for a range of existing treatments, including stem cell transplants and commercial CAR-T cell therapies. The demand for these collections has surged, particularly with the potential eligibility of around 3,000 diffuse large cell lymphoma patients per year for CAR-T cell therapy, introducing delays and new risks. The rapid expansion of CGTs has outpaced the development of industry standards, creating an opportunity for optimization in collection processes and services, thereby enhancing CGT manufacturing.
Ensuring the best-quality cell collections involves adapting to individual patient needs, especially in conditions like SCD where blood and cell composition may vary. Efforts to standardize data collection are underway, powered by Terumo Blood and Cell Technologies’ Spectra Optia. The widely adopted platform enables the collection of valuable data and collaboration with leading researchers to optimize and standardize processes, ultimately improving quality and reducing patient time in the chair.
As seen through our industry-first apheresis training program for cell therapy manufacturers, we are committed to improving the quality of CGT starting materials. And by raising awareness of the critical role of cell collections, we hope to leverage our global reach and experience to facilitate broader access to both established and cutting-edge therapies.
In November, the UK’s Medicines and Healthcare Products Regulatory Agency authorized the use of Casgevy, developed by Vertex Pharmaceuticals (Europe) Ltd. and CRISPR Therapeutics, making it the first approval of a CRISPR–Cas9 gene editing therapy. This demonstrates another step forward in the development of advanced therapies and paves the way for other CRISPR-based therapies and a potential cure for many genetic diseases.
Casgevy was approved for the treatment of blood conditions sickle-cell disease and transfusion-dependent β-thalassemia, illnesses caused by mutations in the genes that code for hemoglobin. It works by genetically modifying a patient’s hematopoietic stem cells, editing the genes that code for hemoglobin, preventing the production of mutated hemoglobin and stimulating the production of fetal hemoglobin, which does not have the disease-causing mutations.
This is likely just the beginning for Casgevy, which is also under review by the U.S. Food and Drug Administration, the European Medicines Agency, and the Saudi Food and Drug Authority, so further approvals for the gene editing therapy may follow. It also marks a turning point for CRISPR-based therapies, which have come a long way quickly, given the technology was first used for genome editing only a decade ago.
The most consequential event in 2023 in the gene therapy and cell-modified gene therapy sector was the significant increase in approvals over the year. These therapies have been mainly approved for treatment of autoimmune diseases, cancer, infectious or inherited diseases. The new approvals include Vyjuvek, Elevidys and Roctavian, among others.
Importantly, as disclosed by Alliance of Regenerative Medicine (ARM) on its last report, the number of ongoing clinical trials in the cell and gene therapy sector has increased from more than 1000 clinical trials in 2018 to more than 1600 clinical trials in 2023. Consequently, the number of developers has very substantially increased from around 900 developers five years ago by more than three times, to around 2700 developers.
This growth, and the forecasted increased demand of the market, is very positive news for a company fully specialized in the development and GMP manufacture of lentiviral vectors, such as VIVEbiotech, with the aim of developing cell and gene therapies from very early stages up to clinical and commercial phases.
Based these most consequential events, we foresee the industry will need more skilled workers, whose knowhow and established experience will be key for the success and support from the late-stage clinical phase up to commercialization. This is the key reason why, since 2015, VIVEbiotech as a company has remained fully specialized in lentiviral vectors, enhancing our capabilities and expertise through a highly skilled team with a very low turnover rate.
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