Biosimilars: A Brave New World but Uncertain Terrain
By Chase Doyle
Since the late 1990s, drugs made from living cells have led to therapeutic breakthroughs in previously intractable diseases like HER2-positive breast cancer, cutaneous T-cell lymphoma, and even rheumatoid arthritis, but they’ve also led to an exponential rise in healthcare costs.
According to pharmacy benefit managers (PBM), Express Scripts, biologics are used by only 2% of the population but account for 40% of prescription drug spending in the U.S.
Enter biosimilars, a burgeoning pathway for potentially lower-cost alternatives. Biosimilars are chemically similar, but not identical, to their reference product, and must provide the same safety and efficacy of previously approved agents – an enormous investment in manufacturing precision – but matching one complicated macromolecule to another is only part of the story.
How the Federal Drug Administration (FDA) regulates issues like extrapolation, interchangeability, and even naming criteria will weigh heavily on the direction and resolution of a specialty market set to surpass $250 billion in 2017.
With that kind of money at stake, pricing and reimbursement for biosimilars must be considered, too, and the increasingly aggressive tactics of PBMs suggest the scramble’s just getting started.
At the National Comprehensive Cancer Network’s (NCCN) recent policy summit: Developments in Biosimilars and Molecular Testing, oncology stakeholders reflected on the tectonic changes afoot.
In 2010, under the Affordable Care Act, Congress created an abbreviated licensure pathway for biosimilar products. So far, the FDA has approved 3 biosimilar products, but only one is related to oncology, Sandoz’ Zarxio, for the treatment of chemotherapy-related side effects (biosimilar to Amgen’s Neupogen).
The other biosimilar products are non-cancer related: Pfizer’s Inflectra, a treatment for arthritis and other inflammatory conditions (a version of Johnson & Johnson’s Remicade); and Sandoz’ Erelzi, approved in August, for multiple inflammatory diseases (biosimilar to Enbrel by Amgen and Pfizer).
Since its approval, Zarxio has been steadily eroding Amgen’s market share—Neupogen sales fell to the tune of 23% last quarter.
This pace of approval may resemble a trickle, but closer inspection of the pipeline suggests the dam’s about to break.
Amgen reports 6 biosimilars in various stages of development: bevacizumab, cetuximab, adalimumab, infliximab, rituximab, and trastuzumab.
In July, results from a Phase 3 study evaluating the efficacy and safety of ABP 980 compared with trastuzumab (Herceptin) in patients with HER2-positive early breast cancer ruled out inferiority.
Herceptin, a multibillion-dollar drug, has transformed treatment for approximately 25% of breast cancer patients, and Amgen’s not the only drug maker vying for Genentech’s targeted therapy. There are 6 different biosimilars in development for Herceptin alone.
Genentech’s Avastin, used to treat colorectal, lung, glioblastoma, kidney, and ovarian cancer, is also in the crosshairs. According to Jeffrey Crawford, MD, Associate Director of Clinical Cancer Research at the Duke Cancer Institute, there are 5 biosimilars to Avastin in development, and for the blood-cancer drug Rituxan (also Genentech), 3 are in development.
By the end of 2016, Sandoz plans to submit 11 biosimilar molecules for regulatory approval, and by 2018, said Dr. Crawford, the company will expand the pipeline with 6 additional molecules.
Of course, development by no means ensures approval. Regulators rejected Sandoz’ biosimilar of Neulasta in July and denied approval for Pfizer’s biosimilar of Epogen late last year. Nevertheless, according to Allied Market Research, biosimilars are expected to generate up to $35 billion in global revenue by 2020.