FDA BRIEF: Week of May 22, 2017
ACTEMRA (tocilizumab) injection
Genentech
SUPPLEMENTAL INDICATION: Treatment of giant cell arteritis (GCA) in adult patients
ADDRESSING UNMET NEED:
- Giant cell arteritis is a form of vasculitis causing inflammation of blood vessels
- Standard treatment involves high doses of corticosteroids tapered over time
- First FDA approved therapy specific to vasculitis
REG PATHWAY: sBLA
- Breakthrough Therapy, Priority Review
- Subcutaneous Actemra previously approved for treatment of moderate to severely active rheumatoid arthritis
- Intravenous Actemra previously approved for treatment of moderate to severely active rheumatoid arthritis, systemic juvenile idiopathic arthritis and polyarticular juvenile idiopathic arthritis
EFFICACY:
- Single, randomized, double-blind, multicenter study, n=251 patients with active GCA, 2 SC doses of ACTEMRA vs. 2 different placebo control groups (pre-specified prednisone-taper regimen), 2-week blinded period, followed by a 104-week open-label extension
- Primary efficacy endpoint: Proportion of patients achieving sustained remission from Week 12 through Week 52; defined as absence of GCA symptoms, normalization of inflammatory laboratory tests, tapering prednisone use
- Sustained remission: 56.0% and 3.1% s. 14.0% and 17.6%
SAFETY:
- Generally consistent with known safety profile
- Boxed Warning: Serious infections.
KEYTRUDA (pembrolizumab) injection
Merck
SUPPLEMENTAL INDICATION: Treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
- solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
- colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
ADDRESSING UNMET NEED:
- MSI-H and dMMR tumors contain abnormalities that affect proper DNA repair
- Tumors with these biomarkers commonly found in colorectal, endometrial, gastrointestinal cancers, cancers in breast, prostate, bladder, thyroid gland etc
- First FDA approval based on common biomarker rather than the location in the body where the tumor originated
REG PATHWAY: sBLA
- Previous approvals: Metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, urothelial carcinoma
- Accelerated approval: Based on tumor response rate and durability of response. Continued approval may be contingent upon verification and description of clinical benefit in the confirmatory trials
EFFICACY:
- 5 uncontrolled, open-label, multi-cohort, multi-center, single-arm trials; patients with MSI-H or dMMR solid tumors 2 doses of KEYTRUDA, 15 cancer types, n=149, 24 months
- Major efficacy outcome measures: Objective Response Rate (ORR) assessed by blinded independent central radiologists’ (BICR), RECIST 1.1, Duration of Response (DOR)
- Complete or Partial Response: 39.6%, DOR of 6 mo. for 78% responders
SAFETY:
- Common side effects: Fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation and nausea
- Serious conditions: Immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis
Image credits: FDA, Genentech, Merck