Merck's loss of HCV Breakthrough status shows FDA's pragmatism, says analyst

Grazoprevir/elbasvir, Merck’s once-daily hepatitis C treatment candidate, had its Breakthrough therapy status rescinded last month due to the availability of new drugs - Gilead’s Sovaldi and AbbVie’s  Viekira Pak - that address this medical need.

Breakthrough therapy designation is one of four US Food and Drug Administration (FDA) programmes intended to expedite the approval process for drugs for serious conditions through features like shorter development plans and rolling reviews.

“Breakthrough designation of course doesn’t affect our filing strategy and the data or the data,”​ said Roger Perlmutter, President of Merck Research Labs, during a conference call discussing annual results last week.

“The agency has invited us to comment on their intent to withdraw breakthrough designation, and we intend to have those discussions with the agency. And we will see where that goes, but meanwhile we are moving forward with our program.”​

Christopher Pace, a senior GlobalData analyst covering infectious diseases, agreed this decision would not dramatically slow the approval timeline for Merck’s investigational HCV regimen, but said the FDA will likely take longer to make a decision on the NDA, as Breakthrough Therapy recipients are eligible for Priority Review.

“Therefore, the delay in potential approval – assuming no delay in Merck’s filing of the NDA – is likely to only be a few months,”​ he told in-Pharmatechnologist.com.

Monitoring and revisiting​

Merck’s candidate is the first product to have such a status withdrawn, and so we asked Pace what this meant for the agency.

“One of the requirements for Breakthrough Therapy designation is preliminary clinical evidence that indicates that a drug may demonstrate substantial improvement over existing therapies,”​ he said.

“Therefore, this move is likely an acknowledgment by the FDA that the two recently approved HCV regimens are sufficiently addressing the need for improved therapies to combat HCV, so the FDA does not see Merck’s regimen as providing a substantial improvement over these regimens based on the currently available clinical data.”​

He added that while it is difficult to draw strong conclusions from this decision, it seems “this move may potentially signify a willingness by the FDA to monitor Breakthrough Therapy designations in real time and revisit them in responses to changes in the standard of care in a particular indication and/or therapy areas, as is the case here with HCV.”​

The four FDA expedited programmes for serious conditions are:

• Fast Track designation, featuring actions to expedite development and review, and rolling review
• Breakthrough Therapy designation, featuring intensive guidance on efficient drug development, organisational commitment and rolling review
• Accelerated Approval pathway, featuring approval based on an effect on a surrogate endpoint or an intermediate clinical endpoint that is reasonably likely to predict a drug’s clinical benefit
• Priority review designation, featuring shorter clock for review of marketing application (6 months compared with the 10-monthstandard review)