Growing Controversy Over ‘Skinny’ Labeling for Generic Drugs

The vast majority of patients who initiated imatinib therapy for gastrointestinal stromal tumors (GISTs) received a generic drug that did not have FDA approval for that indication, a large retrospective review showed.

Almost half of the 2,000 patients in the review of imatinib initiators had chronic myeloid leukemia (CML), while about a third had GIST. Three years following the introduction of generic imatinib, more than 90% of patients in both groups received the generic, which had a label indication for CML but not for GIST, reported Bryan S. Walsh, JD, of Brigham and Women’s Hospital and Harvard Medical School in Boston

Overall, 85% of the patients with CML, GIST, or another condition initiated a generic version of imatinib, the group wrote in the Journal of Clinical Oncology.

The findings highlight the FDA-approved practice of “skinny labeling,” which allows generic manufacturers to market their labels that include covered indications, such as CML for generic imatinib, but exclude indications still under patent protection. Skinny labeling is at the center of legal disputes between patent-holding brand-drug companies and generic manufacturers, Walsh told MedPage Today.

The skinny label has its origin in the Hatch-Waxman amendments that established an approval pathway for generic drugs, including the abbreviated new drug application.

“The purpose is to prevent the delay of generic drug approvals as a result of a drug getting subsequent approvals for new diseases after the initial approved indication,” said Walsh. “If a manufacturer were to get another disease approved for their drug, then they would get another patent [that would extend exclusive marketing rights]. Skinny labels allow generic manufacturers to avoid the [patented-protected indications] and get to market in a timely fashion.”

Generic approvals with skinny labeling have become increasingly common in recent years. In a previous study, Walsh and his collaborators identified 56 brand-name drugs with newly approved generics during 2015-2019 with susceptibility to skinny labeling, 24 of which were approved with skinny labels. In the year prior to first generic approval, median net sales of branded drugs with full-label generics was $522 million, whereas median sales of branded drugs with skinny-label generics was $852 million.

In the current study, Walsh and colleagues examined the impact of skinny labeling by means of indication-specific uptake of imatinib. They identified patients covered by private insurance or Medicare Advantage plans who initiated imatinib from February 2016 (when the first generic became available) to September 2020. Generic versions of imatinib approved during that period had skinny labels that included covered indications for CML but excluded GIST.

Of the 2,000 patients included in the analysis, 934 (47%) initiated imatinib for a CML indication, 686 (34%) for GIST, and 380 (19%) for other or unknown indications. Use of generics increased throughout the study period, exceeding 80% in all diagnostic groups by January 2017, one year after the first generic became available.

After adjustment for differences in patient characteristics, generic use on initiation was slightly but significantly higher among patient with CML than for those with the patent-protected indication of GIST (88% vs 85%; HR 0.56, 95% CI 0.39-0.80, P<0.001).

The median copayment for a 30-day supply of generic imatinib was $7 as compared with $40 for branded imatinib (Gleevec). Copayments for generic imatinib were highest for patients with Medicare Advantage plans without a low-income subsidy ($162) and lowest for patients with commercial insurance ($0). Median copayments for branded imatinib ranged from $1,730 for Medicare without low-income subsidy to $0 for commercial, high-deductible insurance plans.

“These findings really put into perspective the difference in median copays,” said Walsh. “If you compare a median copay of $7 for a generic with a median copay of $40 for the brand-name drug, that’s a big gap for a one-month prescription. That’s kind of the key point here. [Skinny labeling] is making drugs more affordable for patients.”

A closely watched legal battle that centers on skinny labeling could have a game-changing effect on the future of skinny labels. Last year a federal appeals court ruled that generic manufacturer Teva infringed on GlaxoSmithKline’s patent protection for the cardiovascular drug carvedilol (Coreg) and reinstated a jury-trial award of $235 million. Legal wrangling continues in that case, but other potential plaintiffs and defendants have taken note.

“We’re starting to see kind of copycat cases coming through the lower courts,” said Walsh. “In one case, it’s not a generic manufacturer that’s being sued but a health insurer, based on its formulary. That’s going to be interesting to watch and see how the courts deal with a new type of defendant.”

To preserve the beneficial effects of skinny labeling, federal regulatory authorities should take the lead in providing guidance, Walsh and coauthors stated.

“[The carvedilol case] has posed a threat to the skinny labeling pathway, as it could discourage generic manufacturers from using this approach to introduce timely generic competition,” they wrote. “To optimize use of the skinny labeling pathway and protect generic manufacturers, the FDA and U.S. Patent and Trademark Office should provide better guidance to manufacturers about how to legally market skinny-labeled generics, and FDA should provide a public list of brand-name products that might qualify for skinny labeling.”