The treatment of neonates greater than or equal to 35 weeks of gestational age with indicators of hemolysis who are at risk of developing severe hyperbilirubinemia.

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Committee: Joint Meeting of the Gastrointestinal Drugs Advisory Committee and the Pediatric Advisory Committee

Indication: The treatment of neonates greater than or equal to 35 weeks of gestational age with indicators of hemolysis who are at risk of developing severe hyperbilirubinemia.

Drug/Device: stannsoporfin injection, for intramuscular use

Sponsor: InfaCare Pharmaceutical Corporation

Links:

Slides:

Points of Consideration:

  1. A single adequate and well-controlled study (Study 64,185-204) was submitted. Consider whether the Applicant:
    1. Assessed the appropriate primary endpoint to demonstrate a clinically meaningful outcome,
    2. Conducted adequate dose exploration in the development program to  determine the lowest effective dose, and
    3. Provided  substantial and highly persuasive evidence of effectiveness of   stannsoporfin as an adjunct to phototherapy in neonates greater than or  equal to 35 weeks gestational age with laboratory evidence of hemolysis and hyperbilirubinemia meeting the AAP criteria for phototherapy for developing complications associated with severe hyperbilirubinemia.
  2. Based on InfaCare’s characterization of the safety profile of stannsoporfin to date in the proposed population, consider:
    1. The adequacy of the overall and short-term safety assessment,
    2. The adequacy of the long-term safety assessment and database to characterize the risk of the potential for stannsoporfin-related adverse neurodevelopmental outcomes.
  3. Discuss whether a Risk Evaluation and Mitigation Strategy (REMS) is needed to ensure the benefits of stannsoporfin outweigh the potential risks.
    1. If you believe a REMS is needed, discuss the merits of the REMS proposed by the FDA, which consists of restricted distribution, health care setting certification, safe use conditions and a registry.   
  4. Consider whether the risk-benefit profile of stannsoporfin supports approval.
  5. If approval is supported, discuss the trial design for a post-approval study to  assess the potential for adverse neurodevelopmental outcomes.

Unique Challenges:

The Joint Gastrointestinal Drugs Advisory Committee and Pediatric Advisory Committee met on May 3, 2018, to discuss the adequacy of data submitted by InfaCare Pharmaceutical Corporation. InfaCare seeks approval for stannsoporfin to treat neonates greater than or equal to 35 weeks of gestational age with indicators

of hemolysis who are at risk of developing severe hyperbilirubinemia. In such patients, inhibition of heme oxygenase may decrease the production of bilirubin which may lead to a clinical benefit when administered in conjunction with phototherapy (PT).

Stannsoporfin is a first-in-class new chemical entity hemeoxygenase inhibitor intended  for the treatment of severe neonatal hyperbilirubinemia. In contrast to current available therapies, which reduce unconjugated bilirubin levels by increasing excretion, stannsoporfin inhibits the production of bilirubin.