Joint investment by pharma giant and CDMO offers transformational model to the whole industry.
French pharmaceutical giant and Swiss-based CDMO Lonza have concluded a joint venture to build and operate a large-scale mammalian cell culture facility for monoclonal antibody (mAb) production at the latter’s site in Visp, Switzerland. Construction, which is expected to cost €270 million, will start this year, overseen by Lonza. The facility should be fully operational by 2020, depending on regulatory approvals.
The two companies will share the available capacity in line with their 50-50 equity shareholdings: Sanofi, which is very active in mAbs, will have additional access to capacity to support increasing demands for its portfolio of biologics, if needed, while Lonza will be free to market its share, if Sanofi does not require it, plus any surplus Sanofi capacity.
This model, the two claimed, “enables Sanofi to react quickly to fluctuations in demand in a short timeframe”, while also providing Lonza with “needed capacities to respond to growing manufacturing demands for large-scale mammalian cell culture based therapeutic proteins … By adding flexibility in this way, this model will help to optimize biologics production capacity across the whole industry.”
Lonza currently has three large-scale biologics facilities at its sites in the U.S. and Singapore. Marc Funk, Chief Operating Officer of the company’s Pharma & Biotech described the platform it is establishing now as the “first module” in an undertaking to “develop further innovative business models based on the requirements of our customers”. The investment will create about 200 jobs at Lonza, plus about ten more embedded Sanofi managers.
Sanofi has already spent heavily on biologics. In 2012, it converted its site at Vitry-sur-Seine near Paris for mAb production and has invested some €250 million there in all since 2010. The company also invested about €300 million at its Sanofi Genzyme site at Geel. Belgium, in 2016, plus €250 million and €100 million respectively at sites in Boston and Frankfurt.
About two thirds of Sanofi’s €3 billion in investment in the period 2015-17 will be spent on biologics. 60% of the company’s R&D pipeline is in this field, covering cardiovascular, immunology and inflammation, neurology and oncology indications, among others. In all, it has 16 compounds in Phase I, 19 in Phase II, nine in Phase III and six undergoing registration, vaccines included.
Among the mAbs prominent in late-stage development at Sanofi are sarilumab, an interleukin (IL)-6 inhibitor that acts against a receptor and blocks pain signals that was co-developed with the biotech Regeneron Pharmaceuticals. This is in the registration phase in the U.S. and the EU for the treatment of patients with active, moderate to severe forms of rheumatoid arthritis (RA).
In May 2016, a comparative trial in 369 patients who had an inadequate response to previous treatment regimens showed sarilumab to be more effective than AbbVie’s Humira (adalimumab) in improving the signs and symptoms of patients with active RA after 24 weeks of treatment.
In December, the U.S. FDA issued a Complete Response Letter to Sanofi, saying that approval would be withheld until certain unspecified deficiencies in the manufacturing system were addressed. This followed a GMP inspection at the Le Trait facility where sarilumab is filled and finished. This could delay launch by several months, but there are no safety issues.
Dupilumab, which was also co-developed with Regeneron, binds to the α sub-unit of the IL-4 receptor, modulating the signaling of the IL-4 and IL-13 pathways. Both of these pathways are associated with the pathophysiology of asthma and atopic dermatitis (AD), the most common form of eczema, among other allergic diseases.
The compound is currently in the registration phase for the treatment of AD, having received FDA designation as a ‘breakthrough therapy’ for uncontrolled moderate to severe AD. The target action date is 29 March. The European Medicines Agency accepted the Marketing Authorization Application for review on December 8, 2016
On March 4, Sanofi and Regeneron presented detailed results from the one-year Phase III ‘Chronos’ study at the Annual Meeting of the American Academy of Dermatology in Orlando, Florida. This built on previous monotherapy data and showed that patients receiving dupilumab with topical corticosteroids (TCSs) achieved significantly improved measures of overall disease severity by comparison with those using TCSs alone to treat moderate to severe AD.
Dupilumab is also in Phase III trials for asthma and nasal polyposis and in Phase II trials for eosinophilic esophagitis. If these come to fruition it could become an even bigger blockbuster than already forecast, taking sales to up to $5 billion/year. Forecasts for use with AD alone range up to $1.8 billion/year.
The last of the three Sanofi mAbs to have reached Phase III is isatuximab, a humanized immunoglobulin G1 mAb developed with ImmunoGen for cancer. Istatuximab targets the CD38 protein via multiple modes of action, killing tumors through direct engagement with the tumor cell while also promoting immunomodulation.
The FDA gave isatuximab orphan drug status for relapsed refractory multiple myeloma in December 2016. This followed promising results in trials that showed the drug to achieves responses in over 50% of patients with these conditions, including those with disease refractory to immunomodulatory drugs, when used in combination with lenalidomide and dexamethasone.
Isatuximab had earlier reached Phase II trials for T-cell leukemia. A Phase III combination trial for plasma cell myeloma comparing pomalidomide and dexamethasone with and without isatuximab is expected to run to 2021.
This month, Sanofi paid €120 million and committed to up to €495 million more in milestone payment to take a stake in AstraZeneca (AZ)’s pipeline mAb, MEDI8897, which has received ‘fast track’ status from the FDA. The two will share costs and profits for the compound, which is about to go into Phase III trials for respiratory syncytial virus (RSV), a disease that is estimated to kill 160,000 children/year.
AZ’s MedImmune subsidiary will head up development until the first approval and split the costs with Sanofi. If MEDI8897 wins approval, Sanofi will lead the commercialization efforts and share the profits equally. AZ will continue to handle manufacturing, while Sanofi will mainly contribute its expertise in vaccines. The two noted that Sanofi also had an infant RSV vaccine in its pipeline but further back, in a niche where many have failed before.