FDA Advisory Committees - FDA Center for Drug Evaluation and Research (CDER) - Oncologic Drugs Advisory Committee (ODAC)
During the morning session, the committee will review and discuss the FDA Reauthorization Act of 2017 (FDARA) mandated Relevant Pediatric Molecular Target List now posted on the FDA website The focus of the discussion will be limited to two target “classes” included in the Relevant Pediatric Molecular Target List: (1) targets linked to cell lineage and (2) targets on normal immune cells and cells in the tumor microenvironment. Planned introductory presentations will be on: (1) cell-based therapy approaches to childhood cancer and (2) novel membrane antigen determinants in pediatric tumors.
During the afternoon session, information will be presented to gauge investigator interest in exploring potential pediatric development plans for two products in various stages of development for adult cancer indications. The subcommittee will consider and discuss issues concerning diseases to be studied, patient populations to be included, and possible study designs in the development of these products for pediatric use. The discussion will also provide information to the Agency pertinent to the formulation of written requests for pediatric studies, if appropriate. The products under consideration are: (1) ONC201, presentation by Oncoceutics Inc., and (2) CD24Fc, presentation by OncoImmune, Inc.
Past Meetings This Year
On Tuesday, May 14, 2019, the Oncologic Drugs Advisory Committee (ODAC) met to discuss two new drug applications (NDAs) submitted by Daiichi Sankyo, Inc. (Daiichi Sankyo).
During the morning session, the committee discussed an NDA for Turalio (pexidartinib) capsules, for the proposed indication to treat adults with symptomatic tenosynovial giant cell tumor (TGCT), also referred to as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS), which is associated with severe morbidity or functional limitations, and which is not amenable to improvement with surgery. A majority of the committee, twelve of 15 members voted that the demonstrated benefit of pexidartinib outweighs the risks for the proposed use.
During the afternoon session, the committee discussed an NDA for quizartinib tablets, for the proposed treatment of adults with relapsed or refractory acute myeloid leukemia (AML), which is FLT3-ITD positive, as detected by an FDA-approved test. A majority of the committee, eight of 11 members, voted that the results of Study AC220-007 do not demonstrate that treatment with quizartinib provides for a benefit that outweighs the risk in the proposed population. (FLT3 = FMS-like tyrosine kinase 3; ITD = internal tandem duplication)
The committee held a half-day (afternoon) meeting to discuss a new drug application (NDA) for selinexor tablets, application submitted by Karyopharm Therapeutics, Inc. (Karyopharm), for use, in combination with dexamethasone, in the treatment of patients with relapsed refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor (PI), at least one immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody.
A majority of the committee, eight of 13 members, voted to recommend delaying selinexor’s approval until results of an ongoing, randomized phase 3 trial, named BOSTON, become available.
The committee discussed the resubmission of a biologics license application (BLA) for CT-P10, a proposed biosimilar of Rituxan (rituximab) by Celltrion, Inc. (Celltrion). Pending licensure, Teva Pharmaceutical Industries, Ltd is responsible for all commercial activities of CT-P10 in the US.
The committee voted unanimously (16 of 16 member) that the totality of the evidence support the licensure of CT-P10 as a biosimilar product of Rituxan for the following three indications:
· relapsed or refractory, low-grade or follicular, CD20-positive, B-cell Non–Hodgkin’s Lymphoma (NHL) as a single agent;
· previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy; and
· non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.
The Committee reviewed and discussed a list of molecular targets for which evidence and/or biologic rationale exist to determine their potential relevance to the growth or progression of one or more pediatric cancers and a list of those targets deemed unlikely to be associated with the growth or progression of pediatric tumors.
A majority of the Committee, 8 of 12 members, voted that the results of the pivotal clinical trial, MT103-203, demonstrate that for patients with acute lymphoblastic leukemia (ALL) in complete response (CR) who have minimal residual disease (MRD) > 0.1%, treatment with blinatumomab provides a potential benefit that outweighs the risks from the treatment.
The Committee split their vote, by a vote of 6-Yes to 6-No, with no abstentions, on the benefit-risk profile of Sutent (sunitinib malate), submitted by C.P. Pharmaceuticals International CV, represented by Pfizer, Inc. (authorized US agent) for the proposed indication of adjuvant treatment of adult patients at high risk of recurrent renal cell carcinoma (RCC) following nephrectomy.
In the morning session, the Committee supported, by a vote of 17-Yes to 0-No, with no abstentions, the licensure of ABP-215 as a biosimilar to Genentech/Roche’s Avastin (bevacizumab), submitted by Amgen Inc. (Amgen). Amgen has developed ABP-215 in collaboration with Allergan.
In the afternoon session, the Committee supported, by a vote of 16-Yes to 0-No, with no abstentions, the licensure of MYL-1401O as a biosimilar to Genentech Inc.’s Herceptin (trastuzumab), submitted by Mylan GmbH (Mylan). Mylan is developing MYL-1401O in collaboration with Biocon Ltd.
The Committee supported, by a vote of 10-Yes to 0-No, with no abstentions, the safety and efficacy of tisagenlecleucel by Novartis Pharmaceuticals Corp. (Novartis) for the treatment of pediatric and young adult patients 3 to 25 years of age with relapsed/refractory (r/r) B-cell precursor acute lymphoblastic leukemia (ALL).
The PDUFA date, which is the FDA’s goal date to make an approval decision, is October 3, 2017.
The Committee supported, by a vote of 6-Yes to 1-No, with no abstentions, the safety and efficacy of Mylotarg (gemtuzumab ozogamicin) by Wyeth Pharmaceuticals Inc. (Wyeth), a subsidiary of Pfizer Inc., for the treatment of certain patients with acute myeloid leukemia (AML).
The Committee (ODAC) discussed potential pediatric development plans/written requests for: (1) APX005M, presentation by Apexigen, Inc. (Apexigen); (2) PMO1183 (lurbinectedin), presentation by PharmaMar USA Inc. (PharmaMar); (3) ASP2215 (gilteritinib), presentation by Astellas Pharma Global Development, Inc. (Astellas); (4) Prexasertib, presentation by Dista Products/Eli Lilly and Company (Lilly); and (5) Olaratumab, presentation by Eli Lilly and Company.
The Committee supported, by a nearly unanimous vote of 14-Yes to 1-No, with no abstentions, the licensure of “Epoetin Hospira” as a biosimilar product to US-licensed Epogen/Procrit.
The Committee supported by a vote of 12-Yes to 4-No, with no abstentions, the risk-benefit profile of neratinib maleate by Puma Biotechnology (Puma) for the extended adjuvant treatment of human epidermal growth factor receptor 2 (HER2)-overexpressed/amplified in adult breast cancer patients who have received prior therapy with trastuzumab (US trade name Herceptin).
In the afternoon session, the Committee supported, by a vote of 10-Yes to 3-No, with no abstentions, the risk-benefit profile of L-glutamine by Emmaus Medical, Inc. (Emmaus) for the treatment of Sickle Cell Disease.
The Committee unanimously supported, by a vote of 11-Yes to 0-No, with no abstentions, the safety and efficacy of rituximab/hyaluronidase injection for subcutaneous use, by Genentech, Inc. (Genentech), to treat patients with certain types of lymphoma and leukemia.
The goal date for the FDA to decide on approval (the PDUFA date) is June 26, 2017.
The Committee did not support, by a vote of 0-Yes to 14-No, with no abstentions, the safety and efficacy of Qapzola (apaziquone) for intravesical instillation, by Spectrum Pharmaceuticals, Inc. (Spectrum). The proposed indication is immediate intravesical instillation post-transurethral resection of bladder tumors in patients with non-muscle invasive bladder cancer (NMIBC).
The Pediatric Oncologic Subcommittee of the Oncologic Drugs Advisory Committee (ODAC) considered information pertinent to the formulation of pediatric studies for the following 5 products: (1) VENETOCLAX by AbbVie, Inc.; (2) TAZEMETOSTAT by Epizyme, Inc.; (3) ATEZOLIZUMAB by Roche/Genentech; (4) LOXO-101 by Loxo Oncology, Inc.; and (5) ENTRECTINIB sponsored by Ignyta, Inc. In addition, the Subcommittee gave input in regard to approaches to treat diffuse intrinsic pontine glioma (DIPG).
The Committee did not support approval of rociletinib tablets by Clovis Oncology, Inc. (Clovis). Rociletinib was proposed for accelerated approval in the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation as detected by an FDA-approved test.
A majority of the Committee members voted that the confirmatory clinical trial (named TIGER-3) should be submitted before FDA makes a regulatory decision on the NDA. The Committee’s vote was 12-Yes and 1-No, with no abstentions. The Prescription Drug User Fee Act (PDUFA) goal date for the NDA is June 28, 2016.
On Thursday, November 19, 2015, the Pediatric Subcommittee of the Oncologic Drugs Advisory Committee (ODAC) was presented with information to gauge investigator interest in exploring potential pediatric development plans for two products in various stages of development for adult cancer indications. The subcommittee discussed issues concerning diseases to be studied, patient populations to be included, and possible study designs in the development of these products for pediatric use. The discussion provided information to the Agency pertinent to the formulation of written requests for pediatric studies, if appropriate. The products under consideration were: (1) ABT-414, sponsored by AbbVie, Inc.; and (2) Lenvatinib, sponsored by Eisai, Inc
The discussion among the Committee members supported a positive benefit-risk assessment of necitumumab injection, submitted by Eli Lilly and Company, for use in combination with gemcitabine and cisplatin, for first-line treatment of patients with locally advanced or metastatic squamous non-small cell lung cancer.
The Committees jointly supported, by a vote of 22-Yes to 1-No, the safety and efficacy of talimogene laherparepvec (T-Vec), submitted by Amgen, Inc. (Amgen). T-Vec is an oncolytic immunotherapy proposed for the treatment of patients with injectable regionally or distantly metastatic melanoma.
The ODAC unanimously supported, by a vote of 14-Yes to 0-No, with no abstentions, the safety and efficacy of EP2006, a proposed biosimilar to Amgen Inc.'s Neupogen (filgrastim), submitted by Sandoz, Inc. The proposed indications for this product are the same as Neupogen’s and are: (1) To decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever; (2) for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of adults with acute myeloid leukemia; (3) to reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by marrow transplantation; (4) for the mobilization of hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis; and (5) for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia.
Oncologic Drugs Advisory Committee (ODAC)
ODAC reviews and evaluates data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of cancer and makes appropriate recommendations to the Commissioner of Food and Drugs.