Staying Agile to Bring Therapies to Patients with Rare Diseases

Bringing drugs to market to serve the needs of patients with rare and ultra-rare conditions not only requires exploration of novel disease mechanisms and drug development — it also calls for attention to administration and the burdens of both the disease and the treatment and reconsideration of the way in which the drug is marketed and made available to patients, as well as novel therapy models to treat patients more holistically. Amryt Pharma is dedicated to transforming the lives of patients with rare diseases, including acromegaly, epidermolysis bullosa, lipodystrophy and homozygous familial hypercholesterolemia. In this Q&A, Amryt’s President Americas Sheila Frame discusses the company’s mission and unique approach to achieving it.

David Alvaro (DA): Can you start out by providing some historical background on Amryt, the genesis of the company, and the founding vision?

Shelia Frame (SF): Amryt was founded in 2016 by two individuals. Dr. Joe Wiley, our CEO and a neurologist by training, who has worked in both big pharma and in private equity. He is not only a physician with significant passion who had done research in Parkinson’s disease, but he also understands the financing of pharmaceuticals and biotech. His co-founder and our current CFO and COO is Rory Nealon, who brought biotech experience, mostly in diagnostics and medical devices, as well a great deal of financial and investment savvy. Amryt is actually Dr. Wiley’s middle name, and it originally derives from a South Asian word meaning “elixir from the gods.”

The company was founded on a mission to focus on rare and ultra-rare diseases and to do so in a manner that would change the conventional pharma model. These diseases, particularly the ultra-rare ones, are significantly underserved by the industry, if only because they have small numbers of patients and small numbers of targets from a commercial perspective or a medical affairs perspective. Amryt really began when our founders discovered a particular manufacturing plant in Germany that was developing a product for epidermolysis bullosa (EB), a condition for which there is currently no treatment on the market, and the rest has followed from there.

Our goal and our sense of purpose at Amryt are to grow in rare and ultra-rare diseases through not only development but also through acquisition. We began by licensing-in two products for Europe — metreleptin and lomitapide — and eventually we acquired the company (Aegerion Pharmaceuticals) in order to gain access to the U.S. market.

DA: In that vein, Amryt recently acquired Chiasma and hence their Transient Permeability Enhancer (TPE®) technology. How does that open up new opportunities for the company?

SF: About a year ago we had the opportunity to acquire Chiasma, which allowed us to not only   complement our current footprint in endocrinology but also to gain access to and to own the TPE technology, which enables oral formulation of large molecules. The acquisition gives us a broader platform to expand our focus, including our entry into acromegaly and, in the future, neuroendocrine tumors, with MycapssaTM. We also acquired Chiasma’s group in Israel who developed TPE. We’re very proud to have them on our team and the work that they’re doing to further develop this technology.

DA: Before getting into the launch of Mycapssa, can you provide an overview of acromegaly: the symptoms, diagnostic challenges, burden of disease, and the current standard of care?

SF: It’s great timing to discuss acromegaly, because the Acromegaly Community recently had its patient forum in San Jose, California, where I had the pleasure of attending with about 150 individuals who suffer from the disease, as well as a number who joined remotely. It was a very emotional and impactful experience, for me personally but also for our team. When we first acquired Chiasma, I had the pleasure of meeting Jill Sisco, president of Acromegaly Community, who is a tremendous inspiration, given everything that she has gone through and what she’s been able to build. It’s amazing to see what one person can do and the ripples that they can create in the community.

For these patients, it’s really a long road — it often takes eight to 10 years to get a diagnosis, because the symptoms, especially early on, are vague. It begins with a small, slow-growing, benign pituitary tumor. Some of the early changes can be difficult to notice. Sometimes it is a dentist who first notices the teeth moving. In other cases, the patient experiences headaches and eventually visits a neurologist, and the tumor is seen on an MRI. In some cases, as the tumor grows it presses on the optic nerve and creates vision problems, so it may be an ophthalmologist who first notices the signs. In any case, the journey to a positive diagnosis of a pituitary tumor is long and difficult. When you talk to people after they have been diagnosed, there is a real sense of affirmation, since they typically have known something is wrong for a long time without knowing exactly what. You just want to embrace these people. Our team is very grateful for the privilege of getting to meet with patients and are motivated in everything we do by the desire to help them.

At that point, the first-line treatment is brain surgery, which is a very delicate and difficult procedure. While there continue to be improvements to these surgeries, the benefits are only really pronounced in about half of patients after surgery, where they are essentially cured and do not need immediate medical support afterward. The other half come out of the brain surgery with the worst headache they’ve ever experienced and ongoing symptoms resulting from the pressure from the tumor and the effect that it has on the pituitary gland, ranging from arthritic-like joint aches to regular headaches to incredible fatigue — again, very difficult symptoms that have to be managed.

DA: What is the history behind octreotide and what was the opportunity Amryt saw with this molecule and this community?

SF: Octreotide and other products were first made available years ago to try to help manage those symptoms by stabilizing the hormones that are out of balance as a result of the tumor. The molecule had been on Dr. Wiley’s radar for a while, so the opportunity to take what has required a very painful deep intramuscular injection and reduce that burden on patients was very promising. Chiasma had originally received approval from the U.S. FDA for Mycapssa, the oral formulation of octreotide, in the fall of 2020 — in the middle of the pandemic. Their original launch strategy was based on the idea that most of the patients in the U.S. would be treated in one of 37 pituitary treatment centers.

This wasn’t a successful launch — the product was entering a marketplace that was completely shut down, with neurosurgeons and endocrinologists who were overrun with the pandemic situation and had limited to no in-person access to patients anyway. The launch was disappointing to the market and to the company in terms of its expectations, which was that as much as half of the patient population would seize the opportunity to avoid injections at doctors’ offices or infusion centers. While this original launch established pretty good awareness in those pituitary centers, there was nearly zero awareness in the community.

At the time, Amryt already had a field force deployed in the community rather than in the academic centers, since we were leveraging that footprint to support Myalept for lipodystrophy. This was of course slowed down at the height of the pandemic, but as vaccinations became available and the market started to open up, we were able to resume real access to the community. We closed the acquisition in August 2021, merged the two sales forces at the end of the year and really kicked off in January of this year, relaunching Mycapssa directly into the community.

We focused on the clinical rationale for why a physician would transition a patient to Mycapssa. Our label is very clear: a patient must have responded to and tolerated injectable octreotide or lanreotide (another somatostatin analogue) before they can be considered for Mycapssa. Physicians and patients are starting to see that there is a clinical benefit here beyond avoiding the injection, particularly as we continue to publish data that demonstrates a consistent efficacy and safety profile across three phase III studies.

DA: Has that experience changed your perspective on how rare disease products should be launched?

SF: I’ve been privileged to be in the industry for way more years than I care to admit, but I’ve only been with Amryt for a little over a year, and it’s my first real endeavor in rare disease. There are so many dynamics in play in the marketplace right now: public policy reform, shifts in the involvement of pharmacy benefit managers (PBMs) in rare disease, and so on.

With rare diseases, a commercial strategy needs to be built around directly interacting with and supporting patients. In this case, we established a nursing team, who work directly with patients once they’ve consented and the choice of medication has been made. They work with patients one-on-one, as much as the patient wants, through the onboarding and the titration of the medication, helping patients have better conversations with their physicians.

One of the unique things about acromegaly is that patients who have been treated for a long time may only see their endocrinologist every six months or once a year, with the primary test being the IGF-1 level to determine whether the patient is stable. One thing that I found fascinating at the Acromegaly Community event was a debate between two clinicians about whether the normal lab ranges are always appropriate for individual patients. With rare diseases, physicians really know their patients, so there’s an opportunity to really think past lab tests and listen to patients about what their lives are really like. That’s been very educational for me.

Also, rare diseases require less engagement with payers, since PBMs, for example, are largely driven by rebates and we never have enough patients from their point of view. But we continue to look at the implications of additional restrictions. When you talk to acromegaly patients and listen to their individual stories of what they have to do to advocate to get access to medicine, it’s horrific. Every January, they have to start over again, because every one of the rare disease treatments requires at least prior authorization, if not medical exception.

Companies like Amryt are really focused on trying to support patients as best we can in a fully legally and compliant way to make sure that they’re getting access to the medicine that they need. I’m optimistic that we’re going to be able to have more of those conversations, not only as an industry but also as a community, and I’m optimistic that the pandemic has shifted some of the thinking.

DA: Is there anything you’d like to share about your other products or your pipeline?

SF: We are about to get full European approval for the product that started the company for EB, which is another absolutely horrific illness. The CHMP in Europe has recommended approval, and the EMA will make a final decision at the end of June for a product called Filsuvez®. In the U.S., we are working with the FDA to determine next steps on a pathway for potential approval.

EB is a debilitating, inherited skin disease that causes a person’s skin to be so fragile that it can be injured just from touch and may never fully heal. EB is intensely painful; recurrent blistering and chronic wounds can result in intolerable pain with limited mobility. Children are unfortunately diagnosed very early and then sent home with their parents in bandages, because that’s the only treatment available. It is an incredibly difficult life. I’ve had the pleasure of meeting some of these children, and they are the most optimistic kids; yet they’re subjected to bandage changes every 48 hours, which comes with significant pain. They often lose their toes or fingers, and in severe cases, don’t live beyond their second decade of life, because the condition doesn’t only affect the external skin exposure — it also impacts internal organs, like the esophagus.

We also have metreleptin — which is Myalept® in the U.S. and Myalepta® in other parts of the world — for lipodystrophy, which is another long, difficult diagnosis and is treated mostly but not exclusively by endocrinologists. Metreleptin is an incredibly effective product to help regulate the leptin levels, but a daily subcutaneous injection is a real challenge for these patients, because they often have no subcutaneous fat as a result of the condition. We are very excited about how the TPE technology could transform that space.

Then finally we have lomitapide — Juxtapid® in the U.S. and Lojuxta® in Europe — for treatment of homozygous familial hypercholesterolemia (HoFH), a genetic disorder that often causes patients to have a cardiac event before the age of 10 and can cause early death if not diagnosed.

It’s an interesting dynamic. Our teams are always looking to connect with physicians to find those patients and get them into treatment. In the case of Mycapssa, it’s different — you need to find stable patients and make the switch. With Filsuvez, we will have the first approved product ever when we bring it to market in Europe. We were the first organization to receive positive phase III data in EB, and now we are building a market.

DA: Can you tell me a bit more about some of the services that Amryt offers to patients?

SF: We have a program called Amryt Assist that provides a range of support: co-pay assistance, nursing support and education. We work with HCPs to bring in their patients and have presentations on the disease. We have experts across each of the areas where we are working, including full-time dieticians on staff who support HoFH patients, because diet is an important component for cardiac health. It all comes back to the rare and ultra-rare model: providing holistic services beyond what is offered a hub service or co-pay assistance. As we consider coming into the EB space and actually building a market, how we support those families who are treating these kids is really fundamental to the strategy. With each of our products, the services are a little bit different, but they are all very much holistic.

DA: Do you have any last thoughts to close?

SF: This is a big moment for Amryt as an organization, as we launch our first internally developed product in Europe this year. Of course, as the head of the Americas, I’m also very excited about bringing it to the U.S. Additionally, over the past year we have tripled the size of our U.S. organization, growing from about 40 people to over 100 now. We continue to work on growing this organization quite significantly while remaining purpose-driven, very focused on rare and ultra-rare disease, and expanding our portfolio through both development and acquisition.

Sheila Frame

Sheila Frame serves as President, Americas, where she is also a member of the Amryt Executive Committee. In her role, Sheila leads the overall business of Amryt across North and South America. Prior to Amryt, Sheila held several Worldwide Commercial and country General Management roles with Novartis and Bristol Myers Squibb. Sheila is currently the past-President of the Central New Jersey Chapter of the Healthcare Businesswomen’s Association. She is also a non-executive director of Theratechnologies Inc. Sheila was recognized as a 2019 Woman of Inspiration & Influence by the Women Business Leaders of the US Health Care Industry Foundation. Sheila holds a Bachelor of Arts degree from York University and a Masters of Business Administration degree from Concordia University.

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