Biosimilars may be a significant growth opportunity for generic companies over the next decade, but uncertainty about FDA’s approval pathway still has made some companies skittish.

Until the uncertainty diminishes, companies may be more willing to remain flexible in choosing a pathway for their biosimilar product.

Allergan PLC, for one, has not revealed which pathway it will take for its biosimilar recombinant follicle stimulating hormone (rFSH) currently in Phase I. But President Siggi Olafsson said the company will make sure the package fills BLA requirements, no matter which pathway the application takes.

“Overall I think we need to make sure our package fulfills the BLA,” he said in a Feb. 21 interview at the Generic Pharmaceutical Association annual meeting in Orlando, Fla.

“I think we are looking for the best way of taking the product to the market. … So I think we will reserve a little bit of judgment until we are a little bit closer to the filing time … because there are pros and cons on both routes per se.”

The rFSH biosimilar references Merck Serono SA’s Gonal-f (follitropin). Watson Pharma Inc., which acquired Actavis and has now taken its name, licensed the product from Itero Biopharmaceuticals in 2010 Also see "Watson Biosimilar Tie Up With Itero Plays Into Women's Health Expertise" - Pink Sheet, 19 July, 2010..

Olafsson’s statement does not inspire a lot of confidence in the 351(k) abbreviated pathway for biosimilars, which no sponsor has attempted to use yet.

Nevertheless, he said during a panel discussion with other company CEOs that biosimilars eventually will gain significant market share.

Rep. Henry Waxman, D-Calif., has been more pessimistic, predicting that sponsors would not use the biosimilar pathway because it was too difficult to navigate Also see "Waxman Says Biosimilar Pathway Will Push Applicants To BLA" - Pink Sheet, 22 November, 2010..

Olafsson noted that the conventional BLA pathway already has defined agency review goals and expectations.

“I think we need to see the biosimilar route before we make a call,” he said during the meeting. “Is it worth the hassle? Is it worth the hurdles that were put in place to go down that route versus going down the BLA route?”

FDA has conducted several sponsor meetings and is awaiting the first marketing application Also see "Biosimilar Meeting Requests Increase, But FDA Cancels Some For Lack Of Data" - Pink Sheet, 12 December, 2012..

Olafsson said the agency has been very helpful in early stage meetings and the company will continue taking advantage of opportunities to interact with FDA officials because there are so many unanswered questions.

Among them is when, or if, FDA will declare some of the products interchangeable with their reference products and allow substitution at the pharmacy level.

GPhA is fighting efforts to add reporting and other requirements before a biosimilar can be substituted for a branded biologic. GPhA President and CEO Ralph Neas said he was disappointed that the tactic is being employed ([A#14130221006]).

FDA Commissioner Margaret Hamburg also said in a speech at the meeting that “efforts to undermine trust” in biosimilars and interchangeable products are “worrisome and represent a disservice to patients who could benefit from these lower cost treatments.”

Biosimilar Market To Grow, But When?

While industry and FDA jockey for position, it is becoming clear that the generic industry likely will need a robust biosimilar market eventually.

Doug Long, IMS Health Inc. VP of industry relations, said at the meeting biosimilars will need to succeed because “small molecule generic opportunities dry up.”

Estimated Biologics Compound Annual Growth Rates

2010-2015: 7.7%
2015-2020: 4.8%

Source: IMS Health

That should put more pressure on industry and regulators to develop and approve biosimilars. Long also said biosimilars will have to play an important role in reducing overall health care spending.

“If you’re going to try to get savings out of the health care system in pharmaceuticals, you’re going to have to get some out of the biological area,” he said.

The Obama administration also has proposed using biosimilars to reduce U.S. health care spending. His FY 2012 budget proposal included cutting the biologics marketing exclusivity period from 12 years to seven years so savings would be realized earlier Also see "CMS 2012 Budget Looks To Biosimilars, Brand/Generic Deals To Offset Costs" - Pink Sheet, 21 February, 2011..

Yet the biosimilar market still will take a while to develop. Long said the biologic market will double in size between 2010 and 2020, but biosimilar growth estimates have not come to fruition yet.

“Our guess is the share of the biologic market for biosimilars will be 4% to 10% in the year 2020,” he said. “It doesn’t look like even this modest estimate is going to be able to make it.”

As biosimilars begin to take off, industry officials see market players evolving as well. More consolidation is expected, as is an increasing number of specialty companies (see related story, Also see "Generic Industry Specialization, Consolidation Driven By Rising Product Complexity" - Pink Sheet, 4 March, 2013.).

More FDA Investment Will Help Market

The emergence of FDA’s biosimilar user fee program and staff also should play a role in jump-starting the sector’s growth.

Agency biosimilar efforts remain in their infancy at the moment as it continues to implement the new pathway. Tony Mauro, president of Mylan NV North America, said FDA has to increase its support of the program.

“Just like when Hatch-Waxman was enacted, ideally I would have loved for them to have a separate office … focused on biogeneric approvals,” he said during the meeting. “It’s new. I think it’s continuing to evolve. Certainly more investment on the people side would be helpful.”

Olafsson said industry will have to give FDA some time to develop more guidance, including standards for interchangeability, which he thought likely will begin by 2016.

His call for patience was why he said he disagreed with the fight against efforts by Amgen Inc. and Genentech Inc. to limit automatic substitution.

“FDA needs to have the opportunity, working with us … to lay out how the interchangeability will be,” Olafsson said. “But to call out one company at this point in time I think is premature at best. ... We need to get the guidance from the FDA before we spark this fight.”

The agency already has released three biosimilar guidances, with more expected Also see "Draft Guidances For 2013 Will Grapple With Biosimilars, Track and Trace, Compounding" - Pink Sheet, 11 February, 2013..

Ultimately, patience may be the only option industry has.

FDA officials have indicated technology improvements are complicating the regulatory environment, including the ability to analytically characterize a biologic as well as determine similarity ([A#14130123008]).

Congress created a biosimilar user fee in 2012 as part of the FDA Safety and Innovation Act. It also created a new user fee for generic drugs and reauthorized the prescription drug user fee program Also see "FDASIA Is Signed, Not That White House Wanted Anyone To Notice" - Pink Sheet, 16 July, 2012..

Biosimilar user fees will support pre-IND and IND activities as well as marketing application reviews, but Center for Drug Evaluation and Research Director Janet Woodcock has said the program likely will be under-resourced until the industry grows ([A#14120912007]).

Are Potential Biosimilar Sponsors Still Hesitant About The Pathway Despite Expected Growth?

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