In February 2020, the Food and Drug Administration issued a six-page draft guidance for biosimilar makers seeking licensure for only some of the reference product’s indications. “It’s bare bones for a reason,” said W. Blake Coblentz, Co-Chair, Hatch–Waxman and Biologics Litigation Group at the law firm Cozen O’Connor. “The FDA is encouraging the applicant to come to them and have a dialogue.”
The most-obvious reasons for seeking a “skinny label” approval are active patents that cover a licensed indication of the reference biologic and existing orphan-drug exclusivity. At the American Conference Institute’s Biosimilars and Innovative Biologics meeting last week, Mr. Coblentz pointed out that biosimilar applicants “are not required to provide the FDA with a justification for not seeking licensure for any one indication.” However, if a drug is intended to be designated as interchangeable, the guidance does advise that the manufacturer seek approval for the full slate of reference drug indications.
The guidance allows for the maker of an approved biosimilar to submit a supplement to its original application soon after expiration of the patent that had prevented use for a specific indication. “The FDA targets a six-month timeline for its decision on this supplement,” he commented.
Jenny Johnson, Vice President, Intellectual Property at Endo Pharmaceuticals, specified, “There is no guarantee that the FDA will allow a biosimilar applicant to seek a skinny label. Applicants for interchangeability are encouraged to seek approval for all indications that are available (outside of orphan indications, as those indications are still under patent).”
In our recent post on payers and skinny labels, we indicated that most payers are less inclined to discourage the use of a biosimilar with a skinny label, by excluding its use. After all, payers are not ostensibly responsible for tracking patents. Furthermore, they routinely have to pay for nonapproved uses, especially for cancer therapies in a Medicare-eligible patient, as long as clinical evidence exists to support its use. If they don’t exclude payment or reimbursement for the drug being used outside of its skinny label, are payers potentially guilty of “induced patent infringement”?
Case law cited by Nicholas Mitrokostas, Partner at Allen & Overy LLP, may have some bearing on the question. He cited Amarin v. Hikma, involving the omega-3 acid icosapent ethyl (Vascepa). The generic was not approved as an adjunct to statin therapy to lower cardiovascular risk. Rather, it was approved for only one of the brand’s indications: as an adjunct to diet to reduce triglyceride levels with severe hypertriglyceridemia. In this case, the manufacturer of the generic (Hikma) and the payer HealthNet were named as defendants. The reason for the latter? HealthNet added the generic to its formulary, said Mr. Mitrokostas. “Some HealthNet plans required prior authorization before covering Vascepa versus the generic.” One district court judge denied HealthNet’s motion to dismiss, related to the prior authorization and documentation required (including indication for which it is being used). “The judge concluded that HealthNet’s formulary and prior authorization process could be ‘affirmative acts’ in induced infringement,” stated Mr. Mitrokostas. “This was deemed plausible, but would need to be proven by Amarin.”
Vishal Gupta, Partner and Co-Chair, Healthcare & Life Sciences Practice at Steptoe & Johnson LLP, asked “Could this open up litigation against insurers? We don’t know where this will end up.”
In a situation where an interchangeable biosimilar is automatically substituted for the reference product, the payer may have less risk. The implication may also be that for a product that is not interchangeable but covered under the pharmacy benefit, the pharmacy benefit manager may also be subject to scrutiny for implied infringement.