FDA BRIEF: Week of May  22, 2017

FDA approved


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.

LABEL


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

LABEL


Image credits: FDA, Genentech, Merck

 

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