perspective

Oncology Drug Approvals: Year in Review

2015 Office of Hematology and Oncology Products (OHOP) approvals & expedited review programs.

Richard Pazdur, M.D., Director of the Office of Hematology and Oncology Products

APPROVALS

  • 16 new molecular entities (NMEs): non-small-cell lung cancer, colorectal cancer, breast cancer, melanoma, renal cancer, pancreatic cancer
  • Multiple Myeloma advances: Darzalex (daratumumab), Empliciti (elotuzumab), Ninlaro (ixazomib), and Farydak (panobinostat)
  • Biosimilar products: Zarxio (filgrastim-sndz) a bone marrow stimulant, Unituxin dinutuximab), for pediatric high-risk neuroblastoma

USE OF EXPEDITED REVIEW PROGRAMS

  • Impressive metric: 6 approvals using expedited review programs in Nov. 2015
  • Accelerated Approval: ‘Frequently’ used based upon a surrogate endpoint reasonably likely to predict a clinical benefit, e.g. overall survival
  • Priority Review:  Granted after NDA submission For serious and life-threatening diseases and provides significant improvement in safety or effectiveness over available therapy. Reduces NDA review times from 12 mo (standard) to 8 mo
  • Breakthrough therapy: Granted at IND stage. For expediting development of drugs for serious and life-threatening with preliminary clinical evidence. More dynamic interaction with sponsors to expedite development

APPLICATION TO ONCOLOGY DRUGS

  • Development of “targeted agents” – Greater effectiveness in a specific population and may generally have a more favorable benefit-risk profile
  • Breakthrough therapy designations – High response rates substantially better than available therapy

OHOP CAPABILITIES & ENGAGEMENTS

  • Review team and high standards of review quality
    • OHOP’s oncologists practicing physicians : medical, pediatric oncologists, radiation oncologists, oncology nurses, physician assistants, and oncology pharmacists
    • In addition, statisticians, basic scientists examining clinical pharmacology and toxicology, chemists reviewing manufacturing
  • External Engagement:
    • Advocacy groups and professional organizations
    • Other Agency centers, offices and National Cancer Institute
    • Ex-US regulators to share ideas and concerns
    • Expansion of “patient voice” initiative

 


NEJM

FDA clarification of Flibanserin approval – after 2 rejections !

  • Careful evaluation of efficacy endpoints and clinical meaningful improvement, safety concerns and benefit/risk framework
  • Required additional Phase 3 studies as well as Clin Pharm/ Drug interaction studies
  • Considered generalizability of Ph 3 outcomes to all women likely to be prescribed
  • Factored in external feedback on HSDD’s on women’s sense of identity, emotional well-being, relationships
  • Risk evaluation and mitigation strategy with “elements to assure safe use” (REMS-ETASU) to ensure benefits outweigh increased risk of hypotension and syncope with alcohol
  • Risk management with labeling – Warning and Medication Guide
  • Required post-approval trials with enhanced pharmacovigilance to take further actions if needed

READ


 

FDA approved

novartisArzerra (ofatumumab)  

INJECTION

Indication: Extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive chronic lymphocytic leukemia (CLL).

Reg Pathway: sBLA, Priority Review

Efficacy:

  • Single randomized, open-label  (n=474), patients with  complete or partial response after at least two lines of prior therapy, ofatumumab vs . observation
  • Event rate (progressed or died) : 33% vs. 51%
  • Investigator-assessed median Progression Free Survival : 29.4 mo. vs. 15.2 mo. (p<0.0001)

 

arzerra
Safety:

  • Most common adverse reactions: infusion reactions, neutropenia and upper respiratory tract infection
  • Most common serious adverse reactions: Pneumonia, pyrexia and neutropenia (including febrile neutropenia)

 

evis exera

EVIS EXERA II TJF-Q180V duodenoscope

with design modifications intended to reduce infection risk

Olympus medical Systems, Center Valley, PA

Intended Use:  Olympus TJF-Q180V duodenoscope with modifications to the device’s design and labeling intended to help reduce the risk of bacterial infections

Unmet Need:

  • Duodenoscopes  have been associated with the transmission of infectious agents, including antibiotic-resistant infections
  • Need to improve safety of duodenoscopes by reducing  risk of fluid leakage into the elevator channel, which in turn can reduce patient exposure to bacteria and other potential infections

Design Modifications:

  • Elevator channel sealing mechanism to create a tighter seal and reduce the potential for leakage of patient fluids and tissue into the closed elevator channel
  • Conduct annual inspections of each scope in use by facilities to identify any wear and tear on the elevator channel sealing mechanism or the presence of attached debris at the scope’s tip, which would require replacement of the potentially contaminated parts.

Reg Pathway:  510(k) for design modifications

  • 2014 FDA letter : Need for remarket notification for the “closed” elevator channel model which had never been cleared for marketing
  • 2015 FDA Safety Communication : Validated instructions for cleaning and disinfecting of TJF-Q180V while the 510(k) under review
  • Voluntary recall of the original TJF-Q180V model from health care facilities and make needed repair
  • Post market surveillance and Annual reporting

fda guidances

hemodialysis

Implanted Blood Access Devices for Hemodialysis

  • Reclassifying implanted blood access devices for hemodialysis, which were preamendments Class III devices, into Class II (special controls) and subject to premarket notification.- requiring 510(k) Submission
  • Describes 510(k) requirements : DEVICE DESCRIPTION, DEVICE MATERIALS, BIOCOMPATIBILITY, PERFROMANCE TESTING, STERILITY & SHELF LIFE, LABELING, ANIMAL & CLINICAL TESTING

READ

 

 

sterility.JPG

Sterility Information for 510(k) Submissions for ‘Sterile’ Devices

  • Clarification of information regarding sterilization processes for 510(k)s for devices labeled as ‘sterile’
  • ‘Sterile’ –  subject to industrial terminal sterilization processes based on microbial inactivation
  • Describes ESTABLISHED and NOVEL methods

READ


 

 

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