Pfenex at the forefront: How a different biosim approach is becoming a disruptive force
When Zarxio (filgrastim-sndz) became the first FDA-approved biosimilar in the U.S. in March, it was clear that the long-awaited arrival of a new era in accessible medicine had come. Less than six months later, the biosimilars industry in the U.S. has made significant headway. On April 28, the FDA issued "Guidance for Industry - Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act (BPCIA) of 2009."
Also in April, the Generic Pharmaceutical Association (GPhA) launched the Biosimilars Council, a group made up of manufacturers and other stakeholders working together to ensure a positive regulatory, reimbursement, political and policy environment for biosimilars. In addition, the Biosimilars Council is the first educational resource about the safety and effectiveness of biosimilars available to the general public, as well as patient groups seeking support and information.
Bert Liang emerges as a biosimilars visionary
At the helm of the council is Bert Liang, MD, PhD, MBA, who not only has taken on the role as chairman, but is also the Founding CEO of Pfenex Inc., a San Diego-based biosimilar development company, which uses a unique, proprietary protein production platform—Pfenex Expression Technology for recombinant protein production—and bioanalytical approach to developing biosimilars. Pfenex’s platform enables the potential for a fingerprint-like identity to a reference product and therefore limits the need for expensive, costly and long clinical trials.
Companies like Pfenex stand to benefit from the FDA’s clarification of the BPCIA, as they advance the foundation for biosimilar penetration and competition in the marketplace. What comes next? Biopharma Dive spoke with Dr. Liang about Pfenex and the role of FDA guidance in supporting the growth of the biosimilars industry in the U.S.
Bullish on biosimilars
“We are very bullish on biosimilars at this point,” said Liang. Pfenex, which raised $50 million in an IPO last summer, spun off from Dow Chemical in December 2009 in order to focus on biosimilar development and production. According to Liang, “Before the spin off, our division was a fee-for-service company focused on high-quality, high-titer protein production, including difficult-to-express proteins, for large biopharma companies.”
“Dow is a $50 billion-plus chemical company, which does bioanalytical analysis really well. As our division grew, Dow built a 35,000 square-foot facility with built-in bioanalytical capabilities to complement the protein production platform,” Liang explained.
Addressing the biosimilar cost conundrum
The main goal of growing a robust, competitive biosimilars industry in the U.S. is to realize the substantial potential cost-savings associated with biosimilars—which have turned out to be roughly 30% to 40% in Europe. The idea is that lower-cost biologics will provide patients with some of the most powerful, effective and therapeutic treatments for cancer, autoimmune diseases and other difficult-to-treat medical conditions.
Ironically, one of the main barriers to entry for companies wanting to participate in biosimilars has been the cost of developing, producing and gaining regulatory approval for these products. According to IMS, the average cost of developing a biosimilar ranges from $100 million to $250 million, compared with $1 million to $4 million for a small-molecule generic.
One of Pfenex’s primary competitive advantages is its ability to significantly decrease the cost associated with developing and gaining approval for a biosimilar candidate. According to Liang, Pfenex’s capabilities reduce not only the cost of production, but also the opportunity cost associated with long development and approval timelines. He said, “On average, it takes a year to produce a protein-production engine they way it’s currently done in the industry. In contrast, Pfenex’s technology can produce a protein-production engine in nine weeks—and then we end up using that protein production engine for commercialization. Because of our technology, we can get there quickly—and save in terms of costs and opportunity costs.”
Decreasing the burden of clinical trials
A significant part of the costs borne by any companies involved in biosimilar development is the need to prove that the biosimilar product is interchangeable with the reference biologic. According to the FDA, “An interchangeable biological product is biosimilar to an FDA-approved reference product and meets additional standards for interchangeability. An interchangeable biological product may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product.”
Generally, in order to prove interchangeability clinical data is needed that demonstrates analytical and functional similarity with the reference product. In addition, often pharmacokinetic and pharmacodynamic studies are also needed; however, there are some exceptions. When Biopharma Dive spoke to Kate Keeping, senior director of biosimilars research at Decision Resources Group in April about the new FDA guidance, including clinical trial guidelines, she said, “Some companies are pushing the envelope by trying to demonstrate that their molecules are so similar to the reference biologic that phase III trials are not needed.”
Pfenex is doing more than pushing the envelope. It’s shifting the entire paradigm for biosimilar development. According to Liang, “Because of our bioanalytical and protein production expertise, Pfenex makes products with high fidelity. We specialize in products that don’t have a sugar molecule in them—a category that includes a lot of monoclonal antibodies. We always aim for biosimilar fingerprint-like interchangeability, which greatly reduces the burden of long, complex, expensive clinical trials.”
A full pipeline
Pfenex currently has eight biosimilars and one generic drug in its pipeline. Its lead candidate, PF582, is a biosimilar version of Lucentis (ranibizumab), which is used to treat retinal diseases and grossed more than $4 billion last year. In February, Pfenex and Hospira announced their $342 million collaborative partnership focused on developing and commercializing PF582 globally. FDA talks have started—and things are moving along nicely, according to Liang.
Other products in development include biosimilar version of Betaseron (interferon-beta-1b) for multiple sclerosis; Forteo (teriparatide) for severe osteoporosis; Neulasta (peg-fligrastim) for neutropenia and Cimzia (certolizumab-pegol) for Crohn’s disease.
Pfenex is at the forefront of the biosimilars revolution as it joins a handful of large biopharma companies—Amgen, Novartis/Sandoz, Pfizer and Biogen/Samsung (Samsung Bioepsis)—in taking on the U.S. market. While Pfenex is in good company, its unique capabilities have positioned it to be a truly disruptive force in “normalizing” the biosimilar production and approval process, and as new FDA guidance continues to clarify the 351 (k) abbreviated approval pathway, things will only get easier.
Stay tuned for our next feature in this series, where we speak with Bert Liang about the recent “patent dance” decision and why the German biosimilars industry is a good role model for the U.S.