In the conclusion of our reporting from the Festival of Biologics USA meeting last week, we covered present effects on the upcoming biosimilar pipeline as well as the area of biosimilar delivery device testing and regulation.
DIFFICULT DECISIONS AHEAD ON THE BIOSIMILAR PIPELINE
Michael Sarshad, Managing Director, Syneos Health Consulting, believes that there are many factors that affect biosimilar development for prospective manufacturers, but “one is often not appreciated in the big picture: Drug categories rarely stay static.” In other words, while competition in a certain category is ongoing, new molecules or biobetters enter the marketplace, which may alter prescribing patterns in the category.
Mr. Sarshad stated, “Your drug class may be shrinking because of advancements in the market (think transitions from adalimumab prescribing to Rinvoq and Skyrizi for immunology and from ranibizumab to Vabysmo and aflibercept HD for the treatment of macular degeneration). Newly introduced mechanisms of action may shift the standard of care.”
The potential for new introductions need to be considered as early as possible during the biosimilar development phase, because they may not only fundamentally change the dynamics of the category in addition to the revenue potential for the biosimilar candidate.
Sean McGowan, Senior Vice President, Biosimilars Sales and Marketing, Amneal Pharmaceuticals, pointed out that the Inflation Reduction Act (IRA) maximum fair price (MFP) provisions also may threaten the biosimilar pipeline. “The IRA may cut the reference product’s net price by 20% or 30% immediately, years before the biosimilar even gets to compete,” he said, which lowers revenue expectations considerably, even during a biosimilar’s early characterization phase of development.
The biosimilar void is a prime example of factors that limit biosimilar candidate research. Mr. McGowan remarked that “we may have to live with higher prices on expensive therapies when there is no biosimilar competition, including many treatments for rare disease or those with lower revenues.“ Return on investment, a major consideration, will be limited, he said.
Sonia Oskouei, PharmD, Vice President and US Head, Biosimilars and Specialty, had another take on the biosimilar void: “The biosimilar void is not a permanent state; rather, it’s a pivotal opportunity to be claimed.” With 118 biologics poised to lose patent protection over the next 10 years, streamlining biosimilar development and speeding their market entry is key to filling the void. Dr. Oskouei added, “Streamlining biosimilar development does not mean using short-cuts but a tailored, regulatory framework for biosimilar development.”
Another key aspect to filling the biosimilar pipeline is to rein in patent abuse and anticompetitive behaviors. “The US has 12 years of marketing exclusivity for biologics (which is the longest in the world), and it is often extended much longer!” according to Dr. Oskouei. One only has to consider Humira and Enbrel, the former with 95 patents had been on the market for 20 years without competition and the latter, for 30 years.
She concluded, “It’s a fundamental issue with the system. Patients ultimately pay at the end of the day. Safeguarding the biosimilars market is essential to unlocking its full promise for patients.”
THE BIOSIMILAR DELIVERY DEVICE CONUNDRUM
Hillel Cohen, PhD, Senior Science Advisor, Biosimilars Forum, raised another ambiguity with the interchangeability designation: If the drug is determined to be interchangeable with the reference product at the time of approval, does that mean the autoinjector or other delivery device is interchangeable as well? In order to consider this thoroughly, Dr. Cohen suggested that the “biosimilar and device is essentially a combination product.”
Like a biosimilar switched for a reference product, patients can be uncomfortable with a new injector device that they have to now use, he said. Of course, it is not as simple as pairing the biosimilar with the reference product’s delivery device. “First of all, the reference product’s device may be outdated or there may be known safety issues with it,” he pointed out, and the biosimilar manufacturer may actually be able to provide a superior instrument. There may also be several patent protection issues related to the device. Dr. Cohen said, “The devices do not have to be identical, but any differences must be evaluated through ‘Threshold Analysis,’” which is an algorithm for evaluating acceptable drug delivery through the device.
“It’s one of the new challenges facing biosimilars,” he stated, “and there can be technical issues resulting in back-and-forth communications with FDA. If there is ‘other than minor differences,’ it could take an additional 6 to 12 months to conduct the necessary human factor studies to prove adequacy.”
Dr. Cohen emphasized that early engagement and communication with the FDA is critical. When an additional human factor study [to assess how a device will be used] is necessary, input by FDA is needed before development of the protocol. According to BsUFA III, first device review should take place within 60 days, “but after the first round of reviews, FDA is off the clock, which means there can potentially be approval delays.”
