FDA Approvals: KISQALI, KEYTRUDA – Drug and Device Digest

FDA BRIEF: Week of March 13, 2017

FDA approved

Image result for kisqaliKISQALI (ribociclib) tablets

Novartis Pharmaceuticals Corporation,  East Hanover, NJ, USA

INDICATION:  In combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)- negative advanced or metastatic breast cancer.

UNMET NEED: Effective new treatment option for the continuing unmet need of the HR+/HER2- advanced breast cancer population.


  • Priority Review, Breakthrough Therapy Designation
  • Post-marketing Requirements: Clinical trial to assess the efficacy and safety of an alternative dosing, clinical pharmacokinetic trial in severe renal impairment

MECHANISM OF ACTION: Inhibitor of cyclin-dependent kinase (CDK) 4 and 6 that are activated and play crucial role in cell  cycle progression and cellular proliferation.


  • Single  randomized, double-blind, multicenter study  (n=668), postmenopausal women with HR-positive, HER2-negative, advanced breast cancer with no prior therap, 21 days, 7 days off, KISQALI plus letrozole vs. placebo plus letrozole
  • Primary Endpoint: Investigator-assessed progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • Pre-planned interim analysis PFS: 27.8% vs. 44.9%, p< 0.0001



  • Most common adverse reactions: Neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain
  • Most common grade 3 or 4 adverse reactions: Neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting
  • Warning and Precaution: Prolongation of QT interval


Image result for keytruda

KEYTRUDA (pembrolizumab) injection

SUPPLEMENTARY INDICATION:  treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy [see Clinical Studies (14.4)].

REG PATHWAY:  Supplemental  BLA

  • Orphan Drug Designation, Breakthrough Therapy Designation, Priority Review, Accelerated Approval
  • Accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.


  • Single multicenter, non-randomized, open-label study, n=210,  patients with relapsed or refractory cHL, KEYTRUDA  every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months
  • Major efficacy outcome measures: Overall Response Rate (ORR), Complete Response Rate (CRR), duration of response,  assessed by blinded independent central review
  • ORR  69% (95% CI: 62, 75); median follow-up 9.4 months
  • Median response duration: 11.1 months
  • Efficacy in pediatric patients extrapolated from results observed in adults.


  • Most common adverse reactions: Fatigue, pyrexia, cough, musculoskeletal pain, diarrhea, rash and hypertransaminasemia
  • Additional common adverse reactions: Dyspnea, arthralgia, vomiting, nausea, pruritus, hypothyroidism, upper respiratory tract infections, headache, peripheral neuropathy, hyperbilirubinemia and increased creatinine
  • Other immune-mediated adverse reactions: hyperthyroidism, pneumonitis, uveitis, myositis, myelitis and myocarditis
  • Safety profile in the pediatric patients similar to adults



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