FDA Actions & Updates
The latest approvals, designations, and new indications from the U.S. Food and Drug Administration for oncology drugs.
Thursday, June 25, 2015
The U.S. Food and Drug Administration has granted priority review designation to MM-398 (irinotecan liposome injection, “nal-IRI”) for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy. MM-398 is a novel encapsulation of irinotecan in a long-circulating liposomal formulation. The activated form of irinotecan is SN-38, which inhibits topoisomerase I.
The FDA have also granted orphan drug designation to MM-398 for this indication. And the FDA previously granted Fast Track designation to the drug for this indication last year.
The FDA’s priority review designation shortens the time to complete a drug’s review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA). The FDA action date for Adcetris for this indication is October 24.
MM-398 has been evaluated in the international Phase III study NAPOLI-1, which included 417 patients with metastatic pancreatic cancer who previously received gemcitabine-based therapy. The data were presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer last year (OT 9/25/14). The primary endpoint of overall survival was met for the MM-398-5FU/leucovorin combination. Median survival times were 6.1 months for the patients receiving the MM-398 combination, 4.9 months for the patients receiving MM-398 alone, and 4.2 months for the patients in the control group receiving 5FU/leucovorin.
The most common grade 3 or higher adverse events in patients receiving MM-398 and 5-FU/leucovorin were neutropenia, fatigue, and gastrointestinal effects.
MM-398 is marketed by Merrimack Pharmaceuticals, Inc., and Baxalta Incorporated.
Friday, June 12, 2015
The U.S. Food and Drug Administration has approved Promacta (eltrombopag) for the treatment of children six and older with chronic immune thrombocytopenia (ITP) who had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Promacta is a once-daily oral thrombopoietin receptor agonist that works by inducing stimulation and differentiation of megakaryocytes from bone marrow stem cells to increase platelet production.
Promacta was previously approved for the use in adult patients with the same condition (OT 12/25/08 issue).
“Young patients with chronic ITP who have either an insufficient response to or side effects from standard therapies have limited treatment options, making this FDA approval of eltrombopag for children six years and older particularly important,” James B. Bussel, MD, Professor of Pediatrics and Pediatric Hematology/Oncology at Weill Cornell Medical College—who was lead investigator of the PETIT study for which Promacta’s approval was based on—said in a news release. “Through the eltrombopag studies, one of which is the largest randomized trial ever performed in children with chronic ITP, we discovered that Promacta—a treatment that can be taken once daily by mouth and shown to be well tolerated—can manage this disorder and help these young patients.”
PETIT and PETIT2
The Phase II PETIT trial, a multi-center, three-part study, investigated the efficacy, safety, and tolerability of Promacta in 52 pediatric patients with previously treated chronic ITP. Part 1 was an open-label, dose finding study; Part 2 was a double-blind, placebo-controlled study; and Part 3 was an open-label extension. Of the patients receiving Promacta, 63 percent met the primary endpoint, which was achieving a platelet count of at least 50Gi/L without rescue therapy at least once between weeks one and six, compared with 18 percent of the patients receiving the placebo achieving that endpoint. Also, 14 percent of the patients receiving Promacta needed rescue therapy overall, compared with 59 percent of the patients receiving the placebo.
Approval for Promacta was also based on data from the PETIT2 study, a multi-center, two-part study to investigate the efficacy, safety, and tolerability of the drug in pediatric patients with previously treated chronic ITP. Part 1 was randomized, double-blind, and placebo-controlled; and Part 2 was an open-label extension. There were 72 patients in the study, and 43 percent of those treated with Promacta achieved a platelet count of at least 50 Gi/L without rescue therapy for at least six out of eight weeks between week five and 12 of treatment, compared with 4 percent of patients treated with the placebo achieving that endpoint. Also, 18 percent of patients treated with Promacta needed rescue treatment during the randomized, double-blind period, compared with 22 percent of patients receiving the placebo. And, among 10 patients receiving other ITP therapy at baseline, 50 percent reduced or discontinued concomitant therapy--mainly corticosteroids--without needing rescue therapy over the randomized and Promacta-only treatment periods.
Safety and Side Effects
Serious side effects associated with Promacta include liver problems, abnormal liver function tests, high platelet counts, and higher risk for blood clots and new or worsened cataracts.
The most common side effects for Promacta are nausea, diarrhea, upper respiratory tract infection, vomiting, muscle aches, urinary tract infection, inflammation in the throat or mouth, abnormal liver function tests, back pain, flu-like symptoms, skin tingling, itching, and rash.
The most common side effects of Promacta in children six years and older when used to treat chronic ITP are: upper respiratory tract infections, nasopharyngitis, rhinitis, abdominal pain, cough, inflammation in the throat or mouth, toothache, abnormal liver function tests, diarrhea, rash, and vitamin D deficiency.
Promacta is marketed by Novartis. The drug is marketed as Promacta in the U.S. and Revolade in most other countries.
Tuesday, June 02, 2015
The U.S. Food and Drug Administration has accepted supplemental Biologics License Application for and has granted priority review designation to the anti-PD-1 therapy Keytruda (pembrolizumab) for the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose disease has progressed on or after platinum-containing chemotherapy and an FDA-approved therapy for EGFR or ALK genomic tumor aberrations, if present.
The FDA’s priority review designation shortens the time to complete a drug’s review and aims to deliver a decision on marketing approval designation for drugs that may offer major advances in treatment or provide a treatment where no adequate therapy exists within six months under the Prescription Drug User Fee Act (PDUFA). The FDA action date for Keytruda for this indication is October 2.
Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, by binding to the PD-1 receptor and blocking the interaction with the receptor ligands. Keytruda releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. Keytruda previously received breakthrough therapy status for this designation for NSCLC last year (OT 11/25/14 issue).
Keytruda has been approved by the FDA previously for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600-mutation positive, a BRAF inhibitor (OT 10/10/14 issue).
Keytruda’s submission for this new application were based on data from the KEYNOTE-001 trial, which were reported at this year’s American Association for Cancer Research Annual Meeting in April (OT 6/10/15 issue).
The drug is marketed by Merck.
Monday, May 18, 2015
The U.S. Food and Drug Administration has granted Fast Track designation to AG-120 for the treatment of patients with acute myelogenous leukemia with an isocitrate dehydrogenase-1 (IDH1) mutation. AD-120 is a first-in-class, oral, selective, potent inhibitor of the mutated IDH1 protein.
The Fast Track designation, established under the FDA Modernization Act of 1997, is designed to facilitate frequent interactions with the FDA review team to expedite clinical development and submission of a New Drug Application for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs. The designation permits the drug developer the opportunity to submit sections of an NDA on a rolling basis as data become available, allowing the FDA to review those materials on a rolling basis as well.
The drug is currently being evaluated in a Phase I clinical trial for this indication and results are expected to be presented at the European Hematology Association Annual Congress in June, according to a news release from the drug company, Agios Pharmaceuticals. A Phase III study to evaluate the drug for this indication is being planned to begin in 2016.
Monday, May 18, 2015
The U.S. Food and Drug Administration has granted orphan drug designation to GMI-1271 for use in combination with chemotherapy for the treatment of patients with acute myeloid leukemia (AML). GMI-1271 is a novel and proprietary E-selectin antagonist that increases the ability of chemotherapy to kill cancer cells.
The Orphan Drug designation—to encourage development of drugs in the diagnosis, prevention, or treatment of a medical condition affecting fewer than 200,000 people in the U.S.—grants a product market exclusivity for a seven-year period if the sponsor complies with certain FDA specifications, as well as tax credits and prescription drug user fee waivers. The designation does not, though, shorten the duration of the regulatory review and approval process.
Approximately 20,830 individuals in the U.S. will be diagnosed with AML this year, and 10,460 will die from the disease, according to estimates from the American Cancer Society.
An open-label, multicenter Phase I/II study to evaluate the safety, pharmacokinetics, and efficacy of GMI-1271 used in combination with chemotherapy for the treatment of adult patients with AML is currently recruiting patients. Preclinical data supporting use of the drug were presented at the 2013 American Society of Hematology Annual Meeting.