FDA Brief: Week of Jan 25, 2016
ZEPATIER, (fixed dose combination product of elbasvi and grazoprevir) tablets
Merck , Whitehouse Station, New jersey, USA
Indication : With or without ribavirin for treatment of chronic HCV genotypes 1 or 4 infection in adults
Unmet Need :
- Hepatitis C can lead to diminished liver function or liver failure
- Most infected people asymptomatic until liver damage becomes apparent
- 3 million Americans are infected with HCV, of which genotype 1 is the most common and genotype 4 is one of the least common
- The approval provides another oral treatment option for patients with genotypes 1 and 4 HCV infections without requiring use of interferon.
Reg Pathway : Breakthrough Therapy designation, Priority Review
Mechanism of Action: Direct-acting antiviral agents against the hepatitis C virus
- Six studies(n=1,373), open label and double-blind, with or without ribavirin, with or without cirrhosis, 12-16 weeks
- Sustained virologic response (SVR) 12 weeks post-treatment : 94-97 % (genotype-1) and 97-100 % (genotype-4)
- To maximize SVR rates : Label provides recommendations regarding length of treatment with or without ribavirin specifically tailored to the characteristics of the patient and their virus
- Warning : Elevations of liver enzymes
- Most common side effects: Fatigue, headache, nausea. With ribavirin, anemia and headache.
HALAVEN ( eribulin mesylate ) injection
Eisai, Woodcliff Lake, New Jersey, USA
Indication : Unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen.
- Liposarcoma is a Soft Tissue Sarcoma(STS) in fat cells
- STS most common in the head, neck, arms, legs, trunk and abdomen
- 12,000 cases of STS diagnosed in US
- Need for therapy with survival benefit
Reg Pathway : sNDA, Orphan Drug designation, Priority Review
Mechanism of Action : Inhibits growth phase of leading to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage.
- Single open-label, randomized, active-controlled trial (n=446.), patients with unresectable, locally advanced or metastatic liposarcoma or leiomyosarcoma, at least two prior systemic chemotherapies (containing anthracyclis) , Halaven vs dacarbazine
- Overall Survival : Statistically significant improvement (p=0.011)
- Progression-free survival: No significant difference in overall population
- No evidence of with advanced or metastatic leiomyosarcoma
- Most common Serious Adverse Reactions: Neutropenia, Pyrexia
- Most frequent Adverse Reactions leading to Discontinuation: Fatigue, thrombocytopenia.
- Most common Adverse Reactions: Fatigue, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia