FDA approved Cyramza (ramucirumab) in combination with paclitaxel as a treatment for advanced or metastatic stomach or gastroesophageal junction adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.
Cyramza now has two FDA approvals for these patients, following an approval in April of Cyramza as a single agent, and was previously granted an Orphan Drug Designation. The latest approval was based on the phase III RAINBOW trial, which compared Cyramza plus paclitaxel to placebo plus paclitaxel. Efficacy endpoints in the trial included overall survival, progression-free survival and objective response rate.
Cyramza is an anti-angiogenic therapy. It is a vascular endothelial growth factor receptor 2 antagonist that blocks the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. Cyramza inhibited angiogenesis in an in vivo animal model.
RAINBOW was a multinational clinical trial initiated in 2010, which randomized 665 patients. Cyramza plus paclitaxel significantly extended median overall survival compared with placebo plus paclitaxel (9.6 months (95% CI: 8.5, 10.8) compared to 7.4 months (95% CI: 6.3, 8.4), respectively (HR=0.81 [95% CI: 0.68, 0.96]; P=0.017).
FDA approved the expanded use of Lymphoseek (technetium Tc 99m tilmanocept) injection for lymphatic mapping in solid tumors, and adding sentinel lymph node detection for breast cancer and melanoma to the approved indications.
The FDA also allowed expanded utilization of Lymphoseek with or without scintigraphic imaging, known as lymphoscintigraphy, to enable pre-operative imaging and mapping of lymph nodes to facilitate node localization during surgical procedures. Lymphoseek is developed by Navidea Biopharmaceuticals Inc.
Lymphoseek is the first and only FDA-approved radiopharmaceutical agent for sentinel lymph node detection, is the only FDA-approved agent for lymphatic mapping of solid tumors, and will be immediately available using existing reimbursement codes for this expanded population of cancer patients.
The expanded approval is supported by data from Navidea’s combined analysis of Lymphoseek’s prospective phase III data in melanoma, breast cancer, and certain head and neck cancers from more than 500 subjects. Findings indicated that Lymphoseek accurately identified lymph nodes for assessment in the trial subjects, and is likely to be predictive of overall node pathology status.
FDA granted a Fast Track designation to MM-398 (nanoliposomal irinotecan injection) for the treatment of patients with metastatic adenocarcinoma of the pancreas who have been previously treated with gemcitabine-based therapy.
Fast Track is designed by the FDA to facilitate and expedite the development and review of drugs that treat serious conditions and fill an unmet medical need.
Merrimack is currently preparing a New Drug Application for the indication. Fast Track designation allows sections of the NDA to be submitted to the FDA as they are completed.
According to Merrimack, the company expects to initiate the NDA submission in 2014 with the goal of completing the NDA submission late in the first quarter or early in the second quarter of 2015.
FDA and the European Medicines Agency have granted MM-398 orphan drug designation in metastatic pancreatic cancer.
MM-398 is a nanoliposomal encapsulation of the chemotherapeutic irinotecan. MM-398 has demonstrated extended circulation in comparison to free irinotecan in the clinical setting. The activated form of irinotecan is SN-38, which functions by inhibiting topoisomerase I and promoting cell death.
FDA granted Orphan Drug Designation to the JCAR015 chimeric antigen receptor product candidate, developed by Juno Therapeutics Inc., for the treatment of acute lymphoblastic leukemia. Phase I trials are currently underway at Memorial Sloan Kettering Cancer Center, Juno’s collaboration partner.
All three of Juno’s CAR T cell product candidates currently in trial, including JCAR015, are based on chimeric antigen receptor technology that employs the body’s immune system to attack cancer cells.
JCAR017, in phase I/II trials at Seattle Children’s Hospital, is being tested for pediatric and young adult relapsed/refractory CD19 positive leukemia.
JCAR014, currently in phase I/II trials at the Fred Hutchison Cancer Research Center, is being tested for relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin’s lymphoma, and acute lymphoblastic leukemia.
FDA has opened a public docket and is requesting comments on proposed criteria for “first generic” abbreviated new drug application submissions.
The purpose is to facilitate FDA’s establishment of review prioritization under the Generic Drug User Fee Amendments of 2012.
Establishing clear criteria for this review prioritization category will allow the agency to appropriately prioritize and track ANDA submissions.
Clear criteria for this category will also lead to less industry confusion and more consistent identification of first generic submissions, the agency said.
FDA is requesting comments and supporting information on the following criteria—a first generic application is any received ANDA:
(1) That is a first-to-file ANDA eligible for 180-day exclusivity, or for which there are no blocking patents or exclusivities; and
(2) for which there is no previously-approved ANDA for the drug product.
FDA believes that these proposed criteria appropriately focus FDA’s resources on approving as quickly as possible, new safe and effective generic drug products for patient use.
The agency said these criteria enable it to prioritize review of a pending ANDA when the date on which the ANDA can be approved alters due to changes in the patent or exclusivity landscape.
Under these proposed criteria, first generic status is predicated largely on circumstances outside agency control, and ones that may change while the ANDA is pending, for example, developments related to the disposition of related patent litigation.
FDA also is seeking comments and supporting information on mechanisms the agency could put in place to facilitate ANDA sponsor submission of such relevant information in a timely manner, in addition to that already required under the regulations.
As a result of such developments, ANDA submissions that originally met the criteria for a first generic submission may no longer meet those criteria, the agency said. For example, the validity of a patent may be upheld in litigation, thereby blocking approval until patent expiration.
The agency is therefore seeking comment on whether it should change the review prioritization for an ANDA that no longer meets the first generic criteria during its review.
Comments must be submitted by Dec. 19. Electronic comments can be submitted to the federal eRulemaking Portal: http://www.regulations.gov.
