Carfilzomib Granted Priority Review in Relapsed Multiple Myeloma
The U.S. Food and Drug Administration granted priority review status to the supplemental new drug application for carfilzomib for the treatment of patients with relapsed multiple myeloma who have received at least one prior therapy. The FDA set a target action date of July 26, 2015. Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. This decision was based on results from the phase 3 international, randomized ASPIRE trial – first presented at the 2014 ASH Annual Meeting and subsequently published in The New England Journal of Medicine – and other relevant data. Currently, carfilzomib is approved for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and have demonstrated disease progression on or within 60 days of completion of the last therapy.
Source: Amgen Inc. press release
FDA Introduces an App that Tracks Drug Shortages
The FDA recently released a mobile app that provides the public and health-care professionals with rapid access to information on drugs in short supply. The app identifies current drug shortages, resolved shortages, and discontinuations of drug products. Drugs in short supply can delay or prevent needed care for patients. Drug shortages may also lead health-care professionals to rely on alternative drug products, which may be less effective or associated with higher risks or costs than the drug in shortage. “The FDA understands that health-care professionals and pharmacists need real-time information about drug shortages to make treatment decisions,” said Valerie Jensen, associate director of the Drug Shortage Staff in the FDA’s Center for Drug Evaluation and Research. “The new mobile app is an innovative tool that will offer easier and faster access to important drug shortage information.” App users can search or browse by a drug’s generic name or active ingredient, and browse by therapeutic category. The app can also be used to report a suspected drug shortage or supply issue to the FDA. The app is available for free download via the iTunes App Store and the Google Play store by searching “FDA Drug Shortages.”
Source: FDA news release
FDA Grants Orphan Drug Designation to AG-348 for Rare Form of Hemolytic Anemia
The FDA has granted AG-348, a first-in-class orally available activator of pyruvate kinase-R (PKR) enzymes, orphan drug designation. The investigational drug is designed to treat pyruvate kinase (PK) deficiency, a rare form of hemolytic anemia. PK deficiency is a severe and rare genetic disease with currently no approved or disease-modifying treatments. The FDA’s Office of Orphan Drug Products grants orphan status to support development of medicines for underserved patient populations, or rare disorders that affect fewer than 200,000 people in the United States. The FDA’s decision was based on results from two phase 1 healthy volunteer studies – a single ascending dose study and multiple ascending dose study – in which AG-348 met its primary endpoints. Data presented at the 2014 ASH Annual Meeting also provided early proof-of-mechanism for AG-348. Based on these findings, phase 2 clinical trials of AG-348 in patients with PK deficiency are planned for the first half of 2015.
Source: Agios Pharmaceuticals, Inc. press release
Link Between Genetic Differences and Warfarin-Related Bleeding Confirmed
In a study published in The Lancet, researchers reported that patients with a genetic sensitivity to warfarin have higher rates of bleeding during the first several months of treatment and benefited from treatment with a different anticoagulant drug. The analysis suggests that using genetics to identify patients who are most at risk of bleeding, and tailoring treatment accordingly, could offer important safety benefits, particularly in the first 90 days of treatment. Genetics has been thought to influence an individual’s sensitivity to warfarin, but this is the first study that was able to confirm that link by leveraging data from the ENGAGE AF-TIMI 48 trial – an international, randomized, double-blind trial in which patients with atrial fibrillation received either a higher dose of edoxaban, a lower dose of edoxaban, or warfarin to prevent blood clots. The research team divided 14,000 study participants into three categories based on genetic makeup: normal responders, sensitive responders, or highly sensitive responders. During the first 90 days, sensitive and highly sensitive responders who received warfarin experienced significantly higher rates of bleeding compared to normal responders. As a result, during this early time period, edoxaban was more effective than warfarin at reducing bleeding in sensitive and highly sensitive responders. “These findings demonstrate the power of genetics in personalizing medicine and tailoring specific therapies for our patients,” said Marc S. Sabatine, MD, MPH, a cardiologist at BWH, Chairman of the TIMI Study Group and senior author of the paper.
Source: Mega JL, Walker JR, Ruff CT, et al. Genetics and the clinical response to warfarin and edoxaban: findings from the randomized, double-blind ENGAGE AF-TIMI 48 trial. Lancet. 2015 March 10. [Epub ahead of print]
First IND Submitted for a Novel Antibody Drug Conjugate Against Lymphomas
An Investigational New Drug (IND) application has been filed with the FDA for a phase 1 clinical trial for ADCT-301, a novel antibody drug conjugate targeting CD25, a cell-surface antigen, which is over-expressed in many patients with lymphomas. The phase 1 clinical trial will commence at four leading oncology centers in the United States, with plans for expansion into two centers in the United Kingdom. The trial will evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of ADCT-301 in patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma. ADCT-301 combines a monoclonal antibody targeting CD25 (the alpha chain of the IL-2 receptor) with a pyrrolobenzodiazepine (PBD) warhead. In preclinical in vivo models, ADCT-301 exhibited strong dose-dependent anti-tumor activity against CD25-positive cell lines at low single doses. In preclinical studies the PBD warhead has been shown to be a highly potent killer of cancer cells even when such cancer cells are resistant to current best therapies. “There is significant unmet medical need for patients with relapsed or refractory disease in Hodgkin and non-Hodgkin lymphoma,” said Steven M. Horwitz, MD, of the Memorial Sloan Kettering Cancer Center and principal investigator of the phase 1 study. “An ADC targeting CD25, which is widely expressed in lymphomas, is a very rational therapeutic approach and could have very broad activity.”
Source: ADC Therapeutics press release