Histamine Dihydrochloride

On May 9, 2017, the U.S. Food and Drug Administration granted accelerated approval to avelumab (BAVENCIO, EMD Serono, Inc.) for patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.Approval was based on data from an open-label, single arm, multi-center study that enrolled 242 patients with locally advanced or metastatic urothelial carcinoma whose disease progressed on or after platinum-based therapy or within 12 months of a platinum-containing neoadjuvant or adjuvant chemotherapy regimen. Patients received avelumab, 10 mg/kg intravenously, every 2 weeks until radiographic or clinical progression or unacceptable toxicity. All patients received pre-medication with an anti-histamine and acetaminophen prior to each avelumab administration. Confirmed overall response rate (ORR) in patients who had been followed for at least 13 weeks was 13.3% (n=30) (95% CI: 9.1, 18.4), and 16.1% (n=26) (95% CI: 10.8, 22.8) in patients who had been followed for at least 6 months. Median time to response was 2.0 months (range 1.3-11.0). The median response duration had not been reached in patients followed for at least 13 weeks or at least 6 months, but ranged from 1.4+ to 17.4+ months in both groups.Deaths due to an adverse reaction occurred in 6% of patients. Serious adverse reactions were reported in 41% of patients. The most frequent serious adverse reactions reported in 2% or more of patients were urinary tract infection/urosepsis, abdominal pain, musculoskeletal pain, creatinine increased/renal failure, dehydration, hematuria/urinary tract hemorrhage, intestinal obstruction/small intestinal obstruction, and pyrexia. The most common adverse reactions that occurred in at least 20% of patients were fatigue, infusion-related reaction, musculoskeletal pain, nausea, decreased appetite, and urinary tract infection.The recommended dose of avelumab is 10 mg/kg as an intravenous infusion over 60 minutes every 2 weeks. Pre-medicate with an anti-histamine and acetaminophen prior to the first four infusions of avelumab. Full prescribing information is available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761078s000lbl.pdfFDA granted this application priority review. FDA approved avelumab for this indication approximately 3 months ahead of the goal date. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).Follow FDA’s Oncology Center of Excellence on Twitter: @FDAOncology

EpiCept Corp says that European regulators have given the green light to Ceplene, the US firm’s treatment for adults with acute myeloid leukaemia. The European Commission has granted a full marketing authorisation in the form of a positive Commission Decision, for Ceplene (histamine dihydrochloride) for the remission maintenance and prevention of relapse in adult patients with AML in first remission. The drug is to be administered in conjunction with low-dose interleukin-2. The approval is based in part on the results of a 320-patient Phase III trial for Ceplene in conjunction with IL-2 which showed that treatment significantly reduced the occurrence of relapse among AML patients in complete remission. The improvement of long-term leukaemia-free survival in patients receiving Ceplene/IL-2 exceeded 50% and the drug was well tolerated. The approval allows Ceplene to be marketed in the 27 member states of the European Union, as well as in Iceland, Liechtenstein and Norway. EpiCept has been granted 10 years of market exclusivity in the EU for the treatment, which has orphan drug status. EpiCept chief executive Jack Talley noted that Ceplene is now the first approved therapy “demonstrated to produce a clear benefit in prolonging leukaemia-free survival and preventing relapse among AML patients”. He added that “several potential commercial partners with established sales infrastructures in haematology and oncology in Europe” have expressed interest in marketing Ceplene and are in "various stages of due diligence". There are 40,000 AML patients in the EU, with 16,000 new cases occurring each year. Once diagnosed, patients typically receive induction and consolidation chemotherapy, with the majority achieving complete remission. However, about 70%-80% of patients who achieve first remission will relapse, within 12 months. Less than 15% of relapsed patients survive long-term. As for the North American market, a pre-New Drug Submission meeting with Health Canada for Ceplene has been scheduled during the fourth quarter and will be followed in the first quarter of 2009 by a meeting with the US Food and Drug Administration.