New Battleground Shaping Up Over Insulin Deliverables

As patents near expiration for insulin products, the newer battles over product exclusivity appear to be focusing on injectors and other delivery systems, according to Stacie Ropka, PhD, and Ted Mathias, intellectual property law partners at Axinn Veltrop & Harkrider.

In March, insulin product approvals were switched to the biologics pathways under the Biologics Price Competition and Innovation Act (BPCIA), which will bring longer periods of exclusivity for innovator products and potentially much greater difficulty for product imitator companies in understanding and challenging product patents, Ropka and Mathias said in a series of 2 interviews set to appear on The Center for Biosimilars^® site this week.

The potential incentive for insulin biosimilar developers under the BPCIA is the prospect for an interchangeability designation, which would make it far easier for biosimilar developers to attain automatic substitution of their products at the pharmacy counter, the attorneys said.

Until recently, insulin products were approved under pathways spelled out in the Hatch-Waxman Act. This changed in March. Insulin products must now be approved under the BPCIA. The BPCIA’s 351(k) application is one of these avenues to approval. It may be less difficult for companies to get approvals under a 351(k) pathway than under Hatch-Waxman but still time consuming and complex, Ropka said.

“Given that the BPCIA has been in effect for 10 years now, and I think we’re up to 28 [biosimilar] products that have been approved by the FDA, the FDA has been able to provide more clarity regarding the types of studies and data they need to review in order to make a decision on approval,” she said. “It can be less difficult to get the data required by the FDA for a robust 351(k) application.”

Lack of clear articulation for insulin product acceptance under Hatch-Waxman was a factor in the scarcity of generic insulin approvals under that legislation, she said.

Penetrating the Patent Nebula

The difficulty for insulin biosimilar approvals under BPCIA stems from the level of patent information about originator products available to biosimilar product applicants.

Under Hatch-Waxman, developers had an advantage in the Orange Book, which outlines patents that cover a reference drug. This has been useful for identifying patent issues in advance that might interfere with bringing a generic drug to market.

However, under Hatch-Waxman, answering these patent issues required preparing letters of notice that cover potential patent infringement and invalidity issues, which can be lengthy to prepare.

Under the BPCIA, the Purple Book is the Orange Book equivalent, and this is a valuable reference guide for drug developers, but the patent information component is missing. “Only the reference product sponsor is in a position to identify patents that might be part of patent litigation or some other type of patent dispute resolution,” Mathias said.

The BPCIA’s patent resolution process “requires the reference product sponsor to provide a list of patents to the follow on developer that they think can reasonably be asserted against the follow on developer in patent litigation, but this list is provided after the follow-on product developer has already made the business decision to pursue a specific biologic and provided the follow-on application to the FDA and to the reference product sponsor. In other words, they’ve already spent quite a bit of money,” Mathias said.

The bottom line is the quality and timing of patent information is not as good for the BPCIA applicant as it was for the applicant under Hatch-Waxman.

Changing the Playing Field Level

There have been recent legislative attempts to improve the situation. One would require that patent information specific to an initial biosimilar application under BPCIA would be added to the Purple Book so that it is available for other biosimilar developers. The problem with that, Ropka noted, is that the information may not be completely relevant to the patent information needs of future drug applicants, and the first applicant to provide that list would have to generate it independently, therefore not having the benefit of readily available information.

It is hoped that drug developers will pursue approvals for insulin products under the BPCIA, but the question is will they be incentivized to do so?

Mathias explained that the pathway for an interchangeable designation under the BPCIA may serve as the incentive that companies are looking for. Interchangeability means a biosimilar can be substituted for a reference product at the pharmacy counter, without the intervention of a physician. “But there's a catch, and the catch is that no biologic has yet been approved as an interchangeable,” he noted. “There are reasons to think that might change soon, but we certainly are not there yet.”

When patents expire on insulin products, biosimilar developers won’t be able to simply step into the vacuum with products of their own, Ropka and Mathias said.

“We’re seeing that reference product sponsors are really focusing on building their portfolios with patents on injectors and other delivery systems,” Mathias explained. Mathias and Ropka expect this to be the new battleground in litigation between originator companies seeking to extend exclusivity for insulin products and biosimilar developers seeking to bring their products to market.

One significant change under BPCIA regards patent exclusivities for insulin products. Insulins previously approved under Hatch-Waxman are not entitled to any further product exclusivity now that they have become biologics “deemed to be approved” under BPCIA.

However, Mathias said, the terms of exclusivity awarded to new products under BPCIA are longer (12 years) than under Hatch-Waxman (maximum of 7 years), so new insulin products approved under BPCIA will not see competition in the form of biosimilars for a long time to come.

In a series of interviews in May, Ropka and Mathias discussed the challenge to the Affordable Care Act (ACA) and how that might affect the future of the BPCIA. If the ACA is fully overturned by the Supreme Court, a new biologics approval pathway would have to be developed, as the BPCIA was approved as part of the ACA.