Resuscitative Endovascular Balloon Occlusion of the Aorta in Patients With Exsanguinating Hemorrhage

Abstract

patent to estimate the maximum added exclusivity the REMS patents could provide.For each drug, we identified the number of REMS patents the generic manufacturers challenged and the outcome of the challenges. Analyses were performed using Excel, version 16 (Microsoft).Results | Of 24 novel small-molecule drugs covered by active, non-class-wide REMS, 5 (21%) had Orange Book-listed REMS patents: alvimopan (Entereg), lenalidomide (Revlimid), pomalidomide (Pomalyst), sodium oxybate (Xyrem), and thalidomide (Thalomid). There was a median of 10 (range, 2-14) REMS patents per drug, comprising a median of 33% (range, 32%-70%) of all patents per drug, which was higher than the median number of active ingredient (1 [range, 0-2]; 5% [range, 0%-17%]), formulation (3 [range, 1-6]; 17% [range, 5%-30%]), or method-of-use (5 [range, 2-15]; 33% [range, 20%-50%]) patents per drug (Table ).Generic entry had occurred for 2 drugs by 2022. For lenalidomide, the date of first generic marketing was 16 months after expiration of the last-expiring REMS patent and 28 months after expiration of the closest expired non-REMS patent. For alvimopan, the date of first generic marketing was more than 9 years before expiration of the last-expiring REMS patent and 3 days after expiration of the first method-of-use patent (Figure). Among drugs with no generic entry, only pomalidomide had an active ingredient patent, which expired 12 months before the last expiring REMS patent. Generic manufacturers challenged 10 lenalidomide, 10 pomalidomide, 7 sodium oxybate, and 14 thalidomide REMS patents, leading to invalidation of 6 sodium oxybate REMS patents and 2 REMS patents each for lenalidomide, pomalidomide, and thalidomide. Discussion | REMS patenting was observed for one-fifth of REMScovered small-molecule drugs and constituted one-third to three-fourths of their patent portfolios. Generic entry occurred after expiration of the last expiring REMS patent for lenalidomide but a decade beforehand for alvimopan. REMS patents for alvimopan were not subject to challenges, while most REMS patents for lenalidomide, pomalidomide, sodium oxybate, and thalidomide were, with a few invalidations. Thus, the association of REMS patents with delaying generic entry has been variable.Study limitations included not being able to evaluate biologics since they do not have the same system of listing their patents with the FDA. 5 REMS can also complicate generic entry in other ways, such as when negotiations are needed to set up shared REMS between brand-name and generic manufacturers. 6 Since some REMS patents may contribute to delays in generic marketing for emerging REMS-covered drugs, to the detriment of patients and the health care system, Congress should consider shielding generic manufacturers from REMS patent infringement claims.