FDA Action Alert: Merck and Amarin – BioSpace

September has been a relatively slow month for the U.S. Food and Drug Administration (FDA). However, there are two PDFUA dates remaining, although one of those took an unexpected turn that will delay it until later in the year.

Merck & Co. has a target action date of September 20, 2019 for its supplemental New Drug Applications (sNDAs) for Pifeltro (doravirine) in combination with other antiretroviral medicines and Delstrigo (doravine/lamivudine/tenofovir disoproxil fumarate) for HIV-1 patients who are switching from a stable antiretroviral regimen and whose virus is suppressed, meaning HIV-1 RNA is less than 50 copies per mL.

Pifeltro is a non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated in combination with antiretroviral drugs for HIV-1 infection in adults with no previous antiretroviral treatment history. Delstrigo is a three-drug combination approved for HIV-1 infection in adults with no antiretroviral treatment history. Of the three-drugs are a non-NNRTI (doravine), and lamivudine and tenofovir disoproxil fumarate, both of which are nucleoside analogue reverse transcriptase inhibitors.

The sNDAs for both Pifeltro and Delstrigo are based on the Phase III DRIVE-SHIFT clinical trial. The trial met its primary endpoint of non-inferior efficacy based on the proportion of patients who switched to Delstrigo and had plasma HIV-1 RNA levels less than 50 copies/mL at Week 48 compared to the same parameters on their baseline regimen with the same criteria at Week 24.

When the sNDAs were accepted in January 2019, Michael Robertson, executive director and section head for HIV and HCV, Merck Research Laboratories, stated, Our clinical development program continues to generate meaningful evidence for Pifeltro and Delstrigo in people living with HIV. We are pleased that the FDA has accepted these supplemental new drug applications. We look forward to continuing our work with the goal of expanding HIV treatment options.

Amarin Corporation has a target action date of September 28 for its sNDA for Vascepa (icosapent ethyl) for the reduction of residual cardiovascular risk in patients whose LDL-C cholesterol is managed by statins but have persistent elevated triglycerides. The drug is under Priority Review, meaning the PDUFA date is four months earlier than the anticipated 10-month reviewsort of, as it turns out. On August 8, the company indicated the FDA has told it that the agency planned to hold an advisory committee meeting, which due to scheduling constraints, would be scheduled at the earliest for November 14, 2019. That would likely push the PDUFA date back to late December 2019, although as of August 8, the company did not know if that was definitive.

The sNDA is based on the REDUCE-IT cardiovascular outcomes trial. The drug is currently approved as an adjunct to diet to reduce triglyceride levels in adults with severe triglyceride levels over 500 mg/dL.

In the REDUCE-IT trial, the drug hit the primary endpoint with a 25% relative risk reduction compared to placebo in the first occurrence of a major adverse cardiovascular event (MACE) in the intent-to-treat population. MACE was defined as a composite of cardiovascular death, nonfatal myocardial infarction (MI or heart attack), nonfatal stroke, coronary revascularization, such as stents and by-pass, and unstable angina requiring hospitalization.

The drug also met the trials key secondary endpoint with a 26% relative risk reduction in 3-point MACE in the study group, with that MACE defined as cardiovascular death, nonfatal heart attack and nonfatal stroke. The drug also hit seven other secondary endpoints, including a 20% relative risk reduction in cardiovascular death compared to placebo. The trial looked at 8,179 statin-treated adults with elevated cardiovascular risk.

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FDA Action Alert: Merck and Amarin - BioSpace