Although one Humira biosimilar already has been approved in the U.S. and others are lining up to take on the global bestseller, Abbvie Inc.'s officials aren't sweating the competition – at least not yet.

They're confident in the patent fence they've built around their cash cow, which produced nearly $16.08 billion in global sales last year, accounting for almost 63 percent of the North Chicago-based company's total net revenue.

The U.S. market for Humira (adalimumab) is pretty much protected until 2022, although biosimilars could launch elsewhere as early as the fourth quarter of 2018, Abbvie Chairman and CEO Richard Gonzalez said on an earnings call Monday. With Humira generating more than $10.4 billion in the U.S. last year, it's a market the company wants to protect as long as possible.

And it's a market other drug companies want a share of. Last September, the FDA approved Amgen Inc.'s Amjevita (adalimumab-atto), but the biosimilar can't hit the U.S. market until key patents expire or are invalidated in court. Meanwhile, Amgen, of Thousand Oaks, Calif., is looking beyond the U.S. It announced Monday that its biosimilar received a positive opinion for marketing authorization from the EMA's Committee for Medicinal Products for Human Use. (See BioWorld Today, Sept. 27, 2016.)

Earlier this month, Boehringer Ingelheim Pharmaceuticals Inc., a unit of Boehringer Ingelheim GmbH, reported that BI 695501, its adalimumab biosimilar candidate, had been accepted for review by both the EMA and the FDA. At least six other companies have biosimilars targeting Humira in Phase III development in the U.S.

In addition to Humira's patent protection, Gonzalez is counting on the biologic being able to hold its own even when biosimilars enter the market. Humira has been competing successfully for years in the rheumatology space with several other TNF-alpha inhibitors, he said.

He's also watching how biosimilars to some of those competitors are doing. Johnson & Johnson's (J&J) Remicade was the first in the class to get biosimilar competition when South Korea approved Celltrion Inc.'s Remsima in 2012 as the world's first official biosimilar monoclonal antibody (MAb).

The EU followed suit the next year, approving the follow-on to be marketed by Celltrion as Remsima and by Hospira Inc. as Inflectra. The follow-ons had a rolling launch based on Remicade's patent expiration, with the launch in some of the major European countries delayed until 2015. Hospira, now part of Pfizer Inc., got FDA approval on Inflectra last year and launched it in September. (See BioWorld Today, Sept. 11, 2013.)

Samsung Bioepis Co. Ltd. added its Remicade biosimilar to the mix when it was approved in the EU last year. Today, Remicade biosimilars have been approved in 66 countries and have pricing or reimbursement in at least 50 countries, Gonzalez said. (See BioWorld Today, Sept. 26, 2016.)

Despite pricing discounts ranging from 15 percent to more than 50 percent, the Remicade biosimilars have so far claimed slightly less than 5 percent of the overall rheumatology market and less than 25 percent of the infliximab market share, Gonzalez noted.

He's also following what's happening with biosimilars to Amgen's Enbrel (etanercept), another competitor in the same class of MAbs. So far, there's one on the market in the EU – Samsung Bioepis' Benepali, which was approved a year ago. As of now, it's been approved in 34 countries and has pricing or reimbursement in 19. It has slightly more than 3 percent of the overall anti-TNF market and 14 percent to 15 percent of the market share for etanercept, Gonzalez said.

(The FDA approved Sandoz Inc.'s Erelzi as a biosimilar to Enbrel in August, but an extended U.S. patent could keep Enbrel biosimilars from launching in the U.S. for a number of years.)

INTERCHANGEABLES A THREAT?

Gonzalez also didn't seem too worried about interchangeables, which unlike biosimilars can automatically be substituted at a retail pharmacy when the reference biologic is prescribed. Few biologics go through a retail pharmacy, as many of them are administered in doctors' offices and they're obtained through specialty pharmacies. Placement on the formulary is what counts with a specialty pharmacy, Gonzalez said.

Commenting on the draft guidance the FDA released a few weeks ago on interchangeability, Gonzalez said it clearly reflects a higher bar for interchangeables and suggests a three-way switching study to demonstrate interchangeability for a biologic like Humira that would be dosed more than once. He added that he doesn't think most of the studies done to date in developing biosimilars would support interchangeability in accordance with the FDA guidance. (See BioWorld Today, Jan. 18, 2017.)

While he expects Humira to continue delivering for Abbvie, Gonzalez has said in the past that he anticipates 30 percent of Humira's "opportunity" will go to biosimilars over time. However, the opportunity itself continues to grow as Humira is approved for new indications and is in demand in more countries. (See BioWorld Today, April 29, 2016.)