US FDA's New Paragraph IV Data Further Illustrates Generic Competition Problems
Executive Summary
Data on the number of ANDAs submitted with valid paragraph IV certifications shows some products with strong generic interest and others with almost none.
The US Food and Drug Administration's enhanced paragraph IV patent certification data continues to illustrate the varying interest of sponsors in developing generics, depending on the product.
A count of the potential first applicant ANDAs submitted, those with valid paragraph IV certifications for at least one patent in an NDA and eligible for 180-day exclusivity, will be included with each new update of agency's paragraph IV patent certification list, along with several other new data points intended to increase transparency.
While the entire 68-page list has not been updated, the entries with the new information show a wide variety of generic interest. Several NDAs had as few as one ANDA applicant, while others had a dozen or more.
The new data further illustrates an ongoing problem in the generic industry that complicates agency efforts to spur competition: while some generic markets are crowded, others, including some with complex formulations, are not.
Products marketed as tablets and capsules often drew multiple potential first filer ANDAs, based on the small sample of products with updated data. Powder, liquid, nasal spray, patch, and gel formulations tended to draw less interest. The size of the potential market also appeared a key factor in the number of ANDAs a brand product attracted.
There were 29 ANDAs submitted with approved paragraph IV certifications for Biogen Inc.'s Tecfidera (dimethyl fumarate) delayed-release capsules, which treat relapsing forms of multiple sclerosis, according to the list. At the same time, there was only one ANDA applicant for Mylan Specialty LP's Dymista (azelastine hydrochloride and fluticasone propionate) nasal spray, intended for seasonal allergic rhinitis.
Sanofi's Aubagio (teriflunomide) tablets, also a treatment for MS, drew 21 ANDAs, while Allergan PLC's Latisse (bimatoprost) topical solution for hypotrichosis of the eyelashes drew only one. (See table below for a sampling of products with updated data.)
Topical products and nasal sprays traditionally have been difficult to genericize, in part because of the drug delivery systems. The FDA is trying to help complex product sponsors navigate the ANDA pathway and hopefully bring more competition to those markets. (Also see "Complex Generic Mid-Cycle Meetings: US FDA Suggests Taking The Date Offered" - Pink Sheet, 7 May, 2019.)
Many generic sponsors also make development decisions well before an ANDA could be submitted, which has hindered other FDA efforts to spur sponsor interest, including the agency's public list of drugs with no generic competition. (Also see "FDA's Off-Patent, Off-Exclusivity List Draws Few Takers Early On" - Pink Sheet, 4 Aug, 2017.)
Information Can Shape Business Decisions
Knowing the number of potential first applicants should prove valuable in streamlining the process of assessing the market for a generic, said Sara Koblitz, an associate at Hyman, Phelps and McNamara PC.
"If you already have a product in development and see that there are already a host of [paragraph IV] ANDAs filed, this information on the list could tell you whether it makes sense to pursue a paragraph IV," she said. "If there is no possibility of 180-day exclusivity and seven putative first-filers, there may not be any real reward for engaging in litigation to challenge a patent."
Attorney Brian Malkin of Arent Fox LLP, said that information also could help FDA control its workload.
"I think that while FDA gets user fees for reviewing ANDAs, they would prefer using agency resources to review ANDAs that have a shot at approval and marketing," Malkin said. "So if this helps companies make decisions whether to develop and file ANDAs, and potentially reduce FDA’s review workload, it would be a win-win."
The FDA also announced 18 June that it is adding 180-day exclusivity decision status, (eligible, deferred, non-forfeiture, or extinguished), 180-day decision posting date, first approval of "first applicant" ANDA date, first commercial marketing date, and last qualifying patent expiration date.
The list previously only contained the active ingredient name, dosage form, strength, reference product name and NDA number, and the first paragraph IV submission date.
The FDA plans to include the new data in all paragraph IV certification list updates going forward and will update existing entries "retrospectively as practicable," according to the agency website.
The new data is part of the FDA's Drug Competition Action Plan, which is intended to spur more generic development and approvals with the hope of reducing drug costs. (Also see "FDA's Generic Policy Initiative Includes Choose-Your-Own-Agenda Meeting" - Pink Sheet, 22 Jun, 2017.)
Information Already Available Through Various Sources
Much of the new information in the paragraph IV list already could be "deduced" from several sources, Koblitz wrote in a blog post about the update. But she said "having it all in one place" and easily accessible will be helpful to sponsors.
Malkin also said that the updated list creates a more level playing field for the information, considering sponsors currently piece it together using court filings, press releases, and FDA decision letters, in addition to the Orange Book.
Acting FDA commissioner Norman Sharpless said in a statement that the data also may help expose the so-called "shenanigans" limiting generic entry that the agency is fighting to curb.
"This data may also provide more public transparency into instances in which the FDA approves an ANDA with exclusivity, but the generic product is not marketed for an extended time, which among other reasons may signal 'gaming' tactics in the generic market," he said.
Legislation is pending that attempts to end the practice of gaining exclusivity but purposely not launching immediately, called exclusivity parking. Industry opposes the idea, arguing it would lower the value of the incentive. (Also see "Generic Industry Market Forces May Impact GDUFA III Talks" - Pink Sheet, 21 Mar, 2019.) The drug pricing package pending in the House also would make pay-for-delay settlements illegal and allow generic companies to sue in order to gain access to samples for testing. (Also see "House Vs. Senate Drug Pricing Bills: A Snapshot Of Differences" - Pink Sheet, 28 May, 2019.)
The FDA has made several attempts of its own to stem patent gaming and other activities intent on preventing generic competition, including publicly warning brand companies of the potential consequences should they not end. (Also see "Gottlieb: Real Risk Of Congressional Action If Anti-Competitive Actions Continue" - Pink Sheet, 3 May, 2018.)