Eight years after a biosimilar path was approved in the U.S. and with 12 approvals under its belt, the FDA is still trying to jumpstart the biosimilar marketplace.

"I'm not satisfied with the current state of the biologics market and biosimilars in particular," FDA Commissioner Scott Gottlieb said at the agency's public hearing Tuesday on enhancing biologic competition.

Approval isn't the problem. It's getting to the marketplace.

In the eight years since Congress passed the Biologic Price Competition and Innovation Act (BPCIA), the FDA has approved 12 biosimilars referencing eight innovators. That's much better than what happened in the EU in the first eight years of biosimilar development there, said Richard Markus, vice president of development for Amgen Inc.'s biosimilar division.

Despite the dozen FDA approvals, not even a handful of biosimilars are being marketed in the U.S. Those that are have had varied reception. The first biosimilar to get FDA approval – Sandoz Inc.'s Zarxio, which references Amgen's Neupogen (filgrastim) – has enjoyed similar uptake in the U.S. as to what it experienced in the EU and elsewhere, Markus said.

But the two biosimilars to Johnson & Johnson's (J&J) Remicade (infliximab) have struggled for market share. Markus attributed their slow start to particular reasons that don't represent the biosimilar market as a whole.

However, Pfizer Inc., which markets Inflectra, one of the Remicade biosimilars, blamed the sputtering performance on reimbursement issues and innovator tactics. "Without market access, a lower-cost biosimilar will not be successful in the U.S.," said Lisa Skeens, vice president of global regulatory affairs at Pfizer. Referencing a citizen petition Pfizer submitted last month, she urged the FDA to issue guidance to combat innovators' "deceptive" market practices aimed at undermining public confidence in biosimilars. The company also has sued J&J, alleging unfair practices to keep competitors off the market. (See BioWorld, Aug. 30, 2018.)

Noting the obstacles facing biosimilars, Christine Simmon, president of the Association for Accessible Medicine's Biosimilars Council, agreed that, by itself, "FDA approval . . . is inefficient" in getting a competitive biologic market up and running. As a result, the U.S. is missing out on big savings. Had all the biosimilars approved last year been successfully marketed, Americans could have saved $4.5 billion, she testified.

PBMs and other obstacles

While many of the obstacles slowing biosimilar development and uptake are outside the FDA's control, Simmon encouraged the agency to use its clout to work with lawmakers and other federal agencies to break down the barriers, which she identified as Medicare reimbursement policies, patent tactics to extend monopolies and restricted access to the reference biologic that's necessary to develop a biosimilar.

A few months ago, the FDA publicly pilloried companies that allegedly made it difficult for would-be competitors to get the drug samples they need to develop generics and biosimilars. The list included 35 drug companies, 51 reference list drugs and 160 inquiries from generic developers. (See BioWorld, May 18, 2018.)

Despite the promise of future updates to the list, Simmon said the disclosure had little impact. "I'm not aware of any companies that have changed their practice as a result of FDA's naming and shaming," she added. A better approach would be to make access to samples a condition of approval.

When it comes to uptake of marketed biosimilars, several speakers blamed pharmacy benefit managers (PBMs) for the slow start of some follow-ons, citing their rebate deals with drug manufacturers that can make pricier drugs more profitable for them.

In the past, many experts predicted that the arrival of interchangeables, which can automatically be substituted at the pharmacy for the prescribed drug, would kickstart competition in the biologic market. Harry Gewanter, medical director at Medical Home Plus Inc., begged to differ, saying that because of PBMs, the approval of interchangeables will not ensure market access. The biologic a patient gets will not be based on cost savings but on which drug the PBM includes on its formulary.

Open formularies with transparent pricing are needed to create a true marketplace, Gewanter said, as he reminded the FDA that "we are, as patients, the ultimate payers – not the insurers and not the PBMs."

Getting a biosimilar approved as an interchangeable – something unique to the U.S. system – has been a slow starter. So far, Boehringer Ingelheim GmbH is the only company to disclose that it's conducting an interchangeability trial on a drug already approved as a biosimilar.

Part of the reason for the sluggish interest is the high bar the FDA has set for demonstrating interchangeability. Boehringer's Molly Burich praised that high bar at the hearing, saying it will build patient and provider confidence in the follow-on.

However, FDA guidance on interchangeables remains scant, as the agency has yet to figure out details such as how to name and label the drugs. Another factor that could be delaying interchangeables is that many biologics are not dispensed at the pharmacy, so interchangeability wouldn't make much of a difference. Markus pointed out that only 10 percent of the biologics that will come off patent in the U.S. by 2023 are distributed through pharmacies.

Purple Book and transitions

While there's not a lot the FDA can do to address many of the impediments to biosimilar uptake, the agency got an earful of opinions and ideas about what it can do during the hearing. For instance, several speakers called for changes in the Purple Book, which identifies biologics, biosimilars and interchangeables.

The current format leaves a lot to be desired, speaker after speaker indicated. They pressed for a searchable, interactive tool that combines the listings of biologics approved by both the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research. (The FDA has them separated into two lists by center.) They also asked for more complete listings that reflect the relationship of biosimilars to the reference product and called on the FDA to include patent information in the Purple Book as it does for the Orange Book listing of small-molecule drugs.

Several speakers also stressed the need for finalized guidance on the transition of proteins from the 505 path of small-molecule products to 351 biologics license applications (BLAs). Under the BPCIA, those drugs are to be deemed biologics by March 23, 2020.

That's just 18 months away, but the FDA has yet to finalize its 2016 draft guidance on how it proposes handling the transition. One of the things left hanging in the draft is what will happen to proteins approved as a 505(b)(2) drug, as the biologics path has no equivalent to 505(b)(2), which partially relies on the safety and effectiveness data for a listed drug. When it released the draft guidance, the FDA said it would leave that discussion for future guidances, which have not been forthcoming. (See BioWorld Today, March 15, 2016.)

That decision could affect the status of insulin and hormone follow-ons that were approved as biosimilars in the EU but as 505(b)(2) drugs in the U.S., including Eli Lilly and Co.'s insulin drug, Basaglar, and Sandoz's growth hormone, Omnitrope.

Several speakers also asked the FDA to rethink the part of the 2016 draft guidance that would strip the transitioned drugs of most of their unexpired 505 exclusivities and not grant them any of the 12-year BLA exclusivity, regardless of how recently they were approved. The orphan drug exclusivity is the only one that would carry over, as it is the same on both paths, according to the guidance.

Other issues discussed at the hearing rehashed points that have been debated since biosimilars became a possibility, including the safety of switching between biosimilars or interchangeables and the use of a nonsensical suffix in the proper name to aid pharmacovigilance. The suffix has become more of an issue since the FDA has reportedly decided not to apply them retroactively to reference biologics.

The FDA will continue to take comments on how best to ramp up biologic competition through Sept. 21.