publication date: Dec. 13, 2019

Drugs & Targets

FDA issues draft guidance to foster pediatric oncology product development

FDA issued a draft guidance document, “FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted Oncology Drugs: Amendments to Sec. 505B of the FD&C Act.”

The draft guidance addresses early planning for pediatric evaluation of molecularly targeted oncology drugs for which original new drug applications and biologics license applications are expected to be submitted to the FDA on or after Aug. 18, 2020, in accordance with section 505B of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which was amended by the FDA Reauthorization Act of 2017 (FDARA).

The draft guidance provides the pharmaceutical industry, clinical investigators and institutional review boards with information to facilitate pediatric studies of molecularly targeted oncology drugs.

Specifically, if an original NDA or BLA is for a new active ingredient, and the drug that is the subject of the application is intended for treatment of an adult cancer and directed at a molecular target the FDA determines to be substantially relevant to the growth or progression of a pediatric cancer, reports on the required molecularly targeted pediatric cancer investigation must be submitted with the marketing application, unless this requirement is waived or deferred.

The draft guidance describes lists, which the FDA sometimes refers to as “The Relevant Molecular Target List” and “The Non-Relevant Molecular Target Leading to Waiver List,” that the FDA plans to update regularly, and that are intended to serve as a guide to sponsors as they consider development plans for new targeted drugs and the need for early pediatric assessments.

“Traditionally, drug development for pediatric cancers lagged, in part, because the requirements to study new cancer drugs in children have been based on whether the cancer occurs in children — and many adult cancers rarely occur in children,” Acting FDA Commissioner Adm. Brett P. Giroir said in a statement. “New, targeted oncology drugs being developed for adult cancers may prove effective in the treatment of some cancers occurring primarily in pediatric patients with similar molecular targets.

“Thanks to amendments to the Federal Food, Drug, and Cosmetic Act made by the FDA Reauthorization Act of 2017, we have a new mechanism to require the evaluation of certain novel cancer medicines for potential pediatric treatment. Our new draft guidance addresses implementation of these amendments, which we anticipate will facilitate early pediatric assessment of certain targeted cancer drugs and accelerate the development of new, safe and effective therapies for pediatric patients.”


FDA approves Avsola for same indications as Remicade

FDA approved Avsola (infliximab-axxq) for all approved indications of the reference product, Remicade (infliximab), including treatment of moderate-to-severe rheumatoid arthritis, moderate-to-severe Crohn’s Disease in the adult and pediatric population, moderate-to-severe ulcerative colitis in the adult and pediatric population, chronic severe plaque psoriasis, psoriatic arthritis and ankylosing spondylitis.

Avsola is sponsored by Amgen.

Avsola, an anti-tumor necrosis factor alpha monoclonal antibody, was proven to be highly similar to Remicade with no clinically meaningful differences based on a totality of evidence which included comparative analytical, nonclinical and clinical data. The data package was composed of, in part, results from a pharmacokinetic similarity study conducted in healthy subjects, and a comparative clinical study conducted in patients with moderate to severe RA.

The randomized, double-blind comparative clinical study evaluated the efficacy and safety of Avsola compared to Remicade in patients with moderate-to-severe RA. There were 558 patients enrolled and randomized (1:1) to receive either Avsola or Remicade at a dose of 3 mg/kg administered as an infusion on day one, at weeks two and six, and every eight weeks thereafter.

The primary endpoint was the response difference of 20% improvement in American College of Rheumatology core set measurements at week 22. Key secondary endpoints included DAS28-CRP change from baseline, RD of ACR20, ACR50 and ACR70 at weeks two, six, 14, 22, 30, 34, 38, 46 and 50. The study also incorporated the evaluation of a single transition in 119 subjects from Remicade to AVSOLA at week 22, which demonstrated similar safety and immunogenicity in patients who were previously on Remicade.

Amgen has a total of 10 biosimilars in its portfolio, four of which have been approved in the United States, and three that are approved in the European Union.


FDA grants Janssen’s BCMA CAR-T therapy JNJ-4528 Breakthrough Therapy Designation for multiple myeloma indication

FDA granted Breakthrough Therapy Designation for the Janssen Pharmaceutical Companies of Johnson & Johnson’s JNJ-68284528 (JNJ-4528), an investigational B cell maturation antigen-directed chimeric antigen receptor T-cell therapy in previously treated patients with multiple myeloma.

The Breakthrough Therapy Designation is supported by data from the phase Ib/II CARTITUDE-1 study (NCT03548207), an open-label, multicenter clinical trial evaluating the safety and efficacy of JNJ-4528 in adults with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy or are double refractory to a proteasome inhibitor and an immunomodulatory drug; have received a PI, IMiD and an anti-CD38 antibody; and who progressed on or within 12 months of their last line of therapy.

Currently active in the United States, the primary objective of the phase Ib portion of the study is to characterize the safety of JNJ-4528 and confirm the dose for future clinical trials. Phase II is evaluating efficacy with a primary endpoint of overall response rate, as defined by the International Myeloma Working Group response criteria, as well as duration of response and overall tolerability.

Initial data from the CARTITUDE-1 study were presented at the American Society of Hematology Annual Meeting.

The CARTITUDE-1 study design was informed by the phase I LEGEND-2 study (NCT03090659), the first-in-human study with LCAR-B38M CAR-T cells. In February 2019, FDA granted Janssen an Orphan Drug Designation for JNJ-4528. On April 3, 2019, Janssen announced the European Medicines Agency granted a PRIME designation for JNJ-4528 based on the CARTITUDE-1 and LEGEND-2 studies.

JNJ-4528, a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies, identifies the investigational product being studied in the U.S. and Europe.

LCAR-B38M, which has the same CAR construct, identifies the investigational product in China. In December 2017, Janssen signed an agreement with Legend Biotech to jointly develop and commercialize LCAR-B38M in multiple myeloma. In China, the Phase II CARTIFAN-1 confirmatory trial (NCT03758417), sponsored by Nanjing Legend Biotech Co. Ltd. in collaboration with Janssen, is actively recruiting to further evaluate LCAR-B38M in patients with advanced relapsed or refractory multiple myeloma.

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