FDA replaces rather than rescinds Merck's breakthrough status
This article was originally published in Scrip
The FDA reversed course on its intention to rescind the breakthrough therapy status it had awarded in October 2013 to Merck for its investigational combination hepatitis C virus (HCV) drug grazoprevir/elbasvir (MK-5172/MK-8742), and now the company holds not one, but two of the coveted designations for the experimental medicine.
The breakthrough status, which is intended to expedite the regulatory process of drugs aimed at treating life-threatening conditions, was initially awarded to Merck for grazoprevir/elbasvir as a treatment for patients with chronic HCV genotype 1 (GT1).
But on 4 February, Merck revealed the FDA had notified the company in late January that regulators were rescinding the designation, citing the availability of other recently approved treatments for GT1 patients.
Gilead Sciences and AbbVie both recently brought new HCV combination drugs to the US market, which have essentially provided a cure for the disease – Harvoni (ledipasvir-sofosbuvir) and Viekira Pak (paritaprevir/ritonavir/dasabuvir), respectively.
Bristol-Myers Squibb received a similar rescind notice in February about two of the breakthrough designations it was awarded for its daclatasvir-based combinations. Spokesman Rob Perry confirmed to Scrip the company had “accepted the FDA’s decision to rescind.”
But rather than rescinding the designation for grazoprevir/elbasvir, the FDA decided to "replace" it for a more focused indication: HCV GT1 in patients with end-stage renal disease on hemodialysis, a Merck spokeswoman told Scrip.
Merck also won a second breakthrough status for the combination drug as a treatment for patients infected with chronic HCV genotype 4.
Grazoprevir is an investigational HCV NS3/4A protease inhibitor and elbasvir is an investigational HCV NS5A replication complex inhibitor.
To gain the breakthrough therapy designation, which was created the Food and Drug Administration Safety and Innovation Act, a drug must be intended to treat a serious condition and have preliminary clinical evidence that indicates the medicine may demonstrate substantial improvement on at least one clinically significant endpoint over available therapies.
As of 20 March – the most recent date for which data are available – the FDA's Center for Drug Evaluation and Research had granted at least 71 of the 244 requests for the breakthrough designation it has received since July 2012, with regulators denying at least 121.
As of 31 March, the FDA's Center for Biologics Evaluation and Research had granted at least 11 of the 49 requests it has received for breakthrough status, denying at least 34.
At least two breakthrough therapy designations have been withdrawn after being granted.