FDA Roundup: New Indication for Hep C Regimen

Daclatasvir / Sofosbuvir – Hepatitis C

The FDA has amended its breakthrough therapy designation for the drug combination of daclatasvir and sofosbuvir for the treatment of hepatitis C. The changes mean that the drug combination may now be used in patients with advanced cirrhosis or in individuals whose infection returns after liver transplant. ¹

The changes come in response to results from the ALLY-1 trial, which found that 12 weeks of the once-daily combination, with ribavirin, worked well in patients with hepatitis C viral genotype 1 and advanced liver cirrhosis (Child-Pugh class B or C).

The drug combination was first granted its breakthrough therapy designation in 2013.
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Evolocumab – Cholesterol

The FDA has released a review of evolocumab, a self-administered injectable drug for the treatment of high cholesterol, in advance of a vote on whether or not to approve the drug, taking place on June 10, 2015. ²

Evolocumab is a proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor, which works by blocking PCSK9 enzymes in the liver and, thereby, lowering the amount of low-density lipoprotein cholesterol in the blood.

The drug’s efficacy was evaluated in 4 phase III, double-blind, randomized trials involving 3152 participants. The trials all evaluated the change in LDL cholesterol from baseline after 12 weeks of receiving 140 mg every 2 weeks or 420 mg once a month.

In another 52-week, double-blind, randomized, placebo-controlled trial of 901 individuals, researchers evaluated the drug’s effect on LDL cholesterol levels from baseline to 52 weeks, with a dosage of 420 mg each month.

Overall, both dosages were associated with significant LDL reductions in about 60% of participants in both the 12-week and 52-week trials.

Reviewers from the FDA expressed concern over the risks associated with the drug of certain cardiac disorders, pancreatitis, appendicitis, pneumonia, and back pain.

They were also concerned with the groups evaluated in the trials, saying, “the overall trial population does not represent a population at high CV risk with substantial CVD burden on maximally tolerated statin therapy—arguably, the most appropriate patient population for add-on therapy to a statin.”

“Potential safety issues identified in this review could be adequately addressed in labeling and by appropriate monitoring and treatment by health care providers,” they noted.

Sirolimus - LAM

The FDA has approved sirolimus, the first drug for the treatment of lymphangioleiomyomatosis (LAM), a rare, progressive lung disease affecting women of childbearing age.³

LAM is found in only 2-5 women per million worldwide, and is characterized by the growth of smooth muscle cells within lung tissue, airways, and blood vessels, destroying the lung.

Sirolimus, known as Rapamune, was originally approved in 1999 as an immunosuppressant for use after organ transplant.

The safety and efficacy of sirolimus in patients with LAM was tested in a clinical trial of 89 patients over a 12-month treatment period, followed by a 12-month observational period.

The difference in forced expiratory volume in one second (FEV1) between treated participants and those taking placebo was 153 mL. During the observational period, in which no participants were taking sirolimus, lung degeneration resumed at a rate comparable to those patients not taking the drug.

Side effects include mouth and lip ulcers, diarrhea, abdominal pain, acne, chest pain, leg swelling, upper respiratory tract infection, dizziness, and elevated cholesterol.

—Michael Potts

References:

1. Bristol-Myers Squibb. Bristol-Myers Squibb receives amended u.s. fda breakthrough therapy designation for investigational daclatasvir-based hepatitis c regimen [press release]. http://news.bms.com/press-release/bristol-myers-squibb-receives-amended-us-fda-breakthrough-therapy-designation-investig. Accessed June 9, 2015.

2. FDA. FDA briefing document: Endocrinologic and Metabolic Drugs Advisory Committee: evolocumab. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM450072.pdf. Accessed June 9, 2015.

3. FDA. FDA approves Rapamune to treat LAM, a very rare lung disease [press release]. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm448523.htm. Accessed June 9, 2015.