FDA granted accelerated approval for Mekinist (trametinib) in combination with Tafinlar (dabrafenib) for unresectable melanoma or metastatic melanoma with BRAF V600E or V600K mutations.
The approval was based on the demonstration of response rate and median duration of response in a phase I/II study, and is dependent on the results of an ongoing phase III trial (MEK115306 or Combi-D). The combination was reviewed under a Priority Review designation.
Improvement in disease-related symptoms or overall survival has not been demonstrated for Mekinist in combination with Tafinlar. The BRAF mutations must be detected by an FDA-approved test. Tafinlar is not indicated for treatment of patients with wild-type BRAF melanoma.
In the phase II portion of the open-label study, the main efficacy endpoint of overall response was 76 percent for patients treated with the combination (n=54; 95% CI, 62, 87), and 54 percent for patients treated with single-agent Tafinlar (n=54; 95% CI, 40, 67).
The median duration of response was 10.5 months for patients treated with the combination (95% CI, 7, 15), and 5.6 months for patients treated with single-agent Tafinlar (95% CI, 5, 7). When enrolling patients, no more than one prior chemotherapy regimen and/or interleukin-2 was permitted. Patients with prior exposure to BRAF inhibitors or MEK inhibitors were ineligible.
Mekinist and Tafinlar are both sponsored by GlaxoSmithKline.
FDA granted 510(k) clearance to Royal Philips’s Spectral Breast Density Measurement Application for its MicroDose SI full-field digital mammography system. The application is the first spectral breast density measurement tool, meaning adipose and glandular tissue can be differentiated to measure volumetric breast density.
The application measures the glandularity and thickness in each pixel of the image to objectively calculate the total volume and volumetric percentage of glandular tissue in the breast. Once the calculations are completed the examination is automatically assigned a MicroDose density score that correlates to the Breast Imaging-Reporting and Data System, the manual method for determining breast density.
The measurement is displayed on the review workstation together in the DICOM tag of the acquired image, and exported for display in a DICOM structured report. The application of non-contrast spectral imaging is made possible by sorting photons into low- or high-energy categories, eliminating the need for two exposures.
FDA approved Miltenyi Biotec’s CliniMACS CD34 Reagent System as a Humanitarian Use Device for the prevention of graft-versus-host disease in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from a matched related donor.
The system removes donor T cells from the graft prior to transplantation by enriching CD34+ blood stem cells, which go on to repopulate the patient’s immune and blood building systems.
Approval was based on data from a phase II, single-arm, multi-center study (BMT CTN 0303) conducted by the Blood and Marrow Transplant Clinical Trials Network.
The trial showed that following intensive myeloablative conditioning, stem cell transplantation from an identical sibling donor processed using the system as the sole means of GVHD prophylaxis lead to a low incidence of chronic GVHD (19 percent at two years after transplantation) without negatively affecting relapse, engraftment, overall survival or disease-free survival.
FDA launched the advisory committee membership nomination portal that allows individuals to submit nominations for membership to any of the agency’s 33 advisory committees.
The portal allows applicants to complete their entire application online. Currently, applications must either be emailed or mailed to the agency.
Nominations for scientific members and consumer and industry representatives may be submitted by professional societies, industry and consumer groups, and other interested persons and organizations.
Potential candidates are asked to provide detailed information concerning such matters as financial holdings, employment, and research grants and/or contracts in order to permit evaluation of possible sources of conflict of interest.
In conjunction with the launch of the nomination portal, the FDA is also posting a set of presentation slides on conflicts of interest for potential members, which can help in answering preliminary questions.
FDA granted an Orphan Drug Designation to BL-8040, developed by BioLineRx, as a treatment for stem cell mobilization, in addition to the orphan designation previously granted to BL-8040 as a treatment for Acute Myeloid Leukemia.
The designation was granted for use of BL-8040 in combination with granulocyte colony-stimulating factor to mobilize human stem cells from the bone marrow to the peripheral blood for collection for autologous or allogeneic transplantation.
BL-8040 is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70 percent of human cancers and its expression often correlates with disease severity. BL-8040 mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer effect by inducing apoptosis.
FDA notified Cell Therapeutics Inc. that the partial clinical hold on tosedostat (IND 075503) has been removed and all studies underway may continue.
Tosedostat is an oral selective inhibitor of aminopeptidases, which provide amino acids necessary for growth and tumor cell survival, and is under development for the treatment of blood-related cancers.
Tosedostat is currently being studied in the U.S. and the European Union in investigator-sponsored and cooperative group-sponsored phase II trials in elderly patients with newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndromes.
FDA and the European Medicines Agency launched a joint initiative to share information on inspections of bioequivalence studies submitted in support of generic drug approvals. This collaboration provides a mechanism to conduct joint facility inspections for generic drug applications submitted to both agencies.
France, Germany, Italy, the Netherlands, and the United Kingdom are also taking part in this initiative.
A key objective of the initiative is to streamline information sharing on inspections of bioequivalence studies conducted and planned for generic drug applications. Inspectional information will be shared for clinical facilities, analytical facilities, or both.
Information will be shared about negative inspection outcomes that reveal system problems at a facility, joint inspections will be conducted at facilities all over the world, and training opportunities will be provided. This initiative will use confidentiality arrangements established among the European Commission, the EMA, interested EU member states, and the FDA.
The agreement includes an 18-month pilot phase and follows the 2009 EMA-FDA Good Clinical Practices Initiative.
The European Commission has amended the product information of Erbitux (cetuximab), updating the indication to include RAS wild-type metastatic colorectal cancer.
The approval follows the positive opinion from the Committee for Medicinal Products for Human Use issued in November 2013, and is based on the totality of data emerging on the role of mCRC RAS tumor status in the benefit-risk profile of the drug. The approval primarily refers to new biomarker data from the OPUS (OxaliPlatin and cetUximab in firSt-line treatment of mCRC) study.
In recent analyses of studies evaluating monoclonal anti-epidermal growth factor receptor antibodies, such as Erbitux, tumor samples of patients with KRAS wild-type tumor status (exon 2) were assessed for additional RAS mutations (defined as mutations in exons 3 or 4 of KRAS and/or exons 2, 3 or 4 of NRAS). The results from these studies suggest that patients with RAS wild-type tumors may benefit from treatment with Erbitux, while patients with RAS mutant tumors may not.
In the updated product information, Erbitux will now be indicated for the treatment of patients with EGFR-expressing, RAS wild-type mCRC in combination with irinotecan-based chemotherapy, in first-line in combination with FOLFOX, or as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan.
Erbitux is sponsored by Merck Serono, the biopharmaceutical division of Merck.
The EU Committee for Medicinal Products for Human Use has recommended approval of Roche’s subcutaneous formulation of MabThera (rituximab) using Halozyme’s recombinant human hyaluronidase (rHuPH20) for the treatment of patients with common forms of non-Hodgkin lymphoma.
Currently, MabThera is delivered by an intravenous infusion which takes approximately 2.5 hours. The new MabThera SC formulation comes as a ready-to-use, fixed dose, 1,400 mg solution.
The CHMP opinion is based primarily on data from Roche’s phase III SABRINA study. Roche expects a final decision from the European Commission in the coming months.
The European Commission granted orphan drug status to Eisai’s amatuximab for the treatment of malignant mesothelioma.
Amatuximab is a chimeric immunoglobulin G-1-kappa (IgG1/kappa) monoclonal antibody with high affinity and specificity for mesothelin, a glycoprotein currently considered an important target of mesothelioma treatment, due to its overexpression on tumor cells.
Amatuximab was discovered and developed through Morphotek, a subsidiary of Eisai.
The National Institute for Health and Care Excellence in the U.K. issued a Final Appraisal Determination for Pixuvri (pixantrone), sponsored by Cell Therapeutics Inc
The positive draft guidance determines Pixuvri is cost effective and recommends funding the treatment as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma.
The NICE Appraisal Committee recommended the treatment as an option for certain people with histologically confirmed aggressive B-cell NHL who have previously received rituximab and are receiving Pixuvri as a third- or fourth-line treatment.
The determination forms the basis of the final guidance to the NHS in England and Wales and is expected to be published in February 2014. Once the final guidance is published, the NHS must fully implement it within 90 days.
Pixuvri is an aza-anthracenedione that forms stable DNA adducts and in preclinical models. It is structurally designed so that it cannot bind iron and perpetuate oxygen radical production, or form a long-lived hydroxyl metabolite—both of which are the putative mechanisms for anthracycline induced acute and chronic cardiotoxicity.
In May 2012, the European Commission granted conditional marketing authorization for Pixuvri as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive NHL.
