After struggling throughout the day with the concept of extrapolation and reliance on structural analytics rather than robust data from pivotal randomized, controlled trials for every indication, the FDA's Arthritis Advisory Committee (AAC) voted 26-0 Tuesday to support the licensure of Amgen Inc.'s Humira biosimilar.

The FDA came into the meeting supporting the drug and the extrapolating of data for several indications in which the biosimilar wasn't tested. Although the agency only required one confirmatory trial, Amgen tested ABP 501 as a biosimilar to Humira (adalimumab, Abbvie Inc.) in two indications: rheumatoid arthritis and plaque psoriasis.

The Thousand Oaks, Calif., biologics maker also is seeking approval, by extrapolation, of five additional Humira indications – juvenile idiopathic arthritis in patients 4 years and older, psoriatic arthritis, ankylosing spondylitis, adult Crohn's disease and adult ulcerative colitis.

If the FDA approves the biosimilar as expected, the follow-on will have a skinnier label than Humira, which still enjoys exclusivity for three other indications, including panuveitis, which was added to its label two weeks ago.

Pleased with the unanimous vote and support for all the available Humira indications, Sean Harper, executive vice president of R&D at Amgen, said the company looks forward to continuing to work with the FDA as the agency completes its review of ABP 501. In its draft questions for the AAC meeting, the FDA noted that it had requested additional data from Amgen regarding the biosimilar's reverse signaling activity. That request is still pending.

With a BsUFA date of Sept. 25, FDA approval wouldn't mean the $14 billion blockbuster Humira will be facing direct biosimilar competition anytime soon. In accordance with a Federal Circuit ruling that has benefited Amgen twice when its Neupogen (filgrastim) and Neulasta (pegfilgrastim) faced biosimilar challenges, the company can't give Abbvie the required 180-day notice of commercial marketing until after the biosimilar is approved. (See BioWorld Today, July 6, 2016.)

However, Abbvie is likely to get more than that six-month reprieve due to the thick intellectual property blanketing its rheumatology/autoimmune blockbuster. The North Chicago innovator has said it doesn't expect direct biosimilar competition until late 2018. And even then, it anticipates Humira will enjoy a strong run through 2020 to 2022. (See BioWorld Today, April 29, 2016.)

By then, Amgen's biosimilar may be one of several approved by the FDA, as at least seven other companies have Humira follow-ons in phase III development, according to Clinicaltrials.gov, and Oncobiologics Inc., of Cranbury, N.J., recently got the FDA nod for its protocol for an integrated biosimilar-interchangeable trial. (See BioWorld Today, July 12, 2016.)

Both Amgen and Oncobiologics are working around Abbvie's formulation patent, but Humira is swathed in more than 60 patents, according to Cortellis.

Humira's U.S. composition -of-matter patent will expire at the end of the year, and a number of other patents will start expiring in 2022, including the main rheumatoid arthritis dosing patent, Jefferies equity analyst Eun Yang reported following Tuesday's adcom.

While Amgen hasn't said much about its launch time and legal strategy for ABP 501, it has indicated it will continue to question the validity of some Humira patents, Yang said. Its inter partes review petition challenging the validity of two patents was denied in January.

ADCOM STRUGGLE

Tuesday's meeting wasn't the AAC's first brush with a biosimilar. In February, it voted 21-3 that the totality of the evidence – which included results from two clinical studies in rheumatoid arthritis and ankylosing spondylitis – supported licensure of Celltrion Inc.'s infliximab biosimilar for nine indications of the reference biologic, Janssen Biotech Inc.'s Remicade. That follow-on, approved in April, will be marketed by Pfizer Inc. in the U.S. as Inflectra. (See BioWorld Today, Feb. 10, 2016, and April 13, 2016.)

Despite that meeting, several committee members still struggled with the concept of biosimilarity and the stepwise approach to developing the follow-ons. Summing up the discussion, David Solomon, AAC acting chairman and a professor at Harvard Medical School, said, "The FDA team attempted – I'm not sure they succeeded – to educate the rest of us about the analytics" that are the foundation to establishing biosimilarity.

Noting how difficult it was for them as experts to get their heads around the concept, the panelists voiced concern about the disconnect patients and some doctors have with biosimilars. That disconnect was evident throughout the comments made during the adcom's lengthy public hearing.

If the biosimilar market is to take off in the U.S., the FDA needs to figure out how to better communicate the follow-ons with the public, said Jennifer Horonjeff, a research fellow and patient advocate at Columbia University Medical Center.

The committee also gave the FDA another charge: Get the much-needed guidance out on biosimilar naming, labeling, extrapolation and interchangeability. Although interchangeability wasn't on the table Tuesday, patients and panelists raised flags about the possibility of payers turning biosimilars into interchangeables by imposing nonmedical switching on patients based on their formularies.