Abbvie Inc., of North Chicago, said the FDA accepted for review a supplemental new drug application (sNDA) for Imbruvica (ibrutinib) in chronic graft-vs.-host disease (cGVHD) after failure of one or more lines of systemic therapy. Imbruvica is jointly developed and commercialized by Pharmacyclics LLC, an Abbvie company, and Janssen Biotech Inc., a unit of Johnson & Johnson, of New Brunswick, N.J. The company's sNDA is based on data from the single-arm phase Ib/II PCYC-1129 trial examining the safety and efficacy of ibrutinib in patients with cGVHD who failed first-line corticosteroid therapy and require further systemic therapy. The Pharmacyclics-sponsored study evaluated 42 previously treated patients with cGVHD in the U.S. who continued on steroid-based regimens. Patients received ibrutinib orally, once daily in combination with ongoing therapies, including corticosteroids and other immunosuppressants, until progression/worsening of cGVHD, recurrence of underlying malignancy or unacceptable toxicity.
Amag Pharmaceuticals Inc., of Waltham, Mass., said the licensing agreement with Endoceutics Inc., of Quebec City, for the U.S. commercial rights to Intrarosa (prasterone) has closed. Intrarosa is the only FDA-approved, locally administered, non-estrogen steroid hormone for the treatment of moderate to severe dyspareunia (pain during intercourse), a common symptom of vulvar and vaginal atrophy, due to menopause. Amag payed $50 million up front and issued Endoceutics 600,000 unregistered shares of stock. As much as $10 million more will be paid on delivery of adequate launch quantities of Intrarosa, and another $10 million on the first anniversary of the effective date of the agreement. The company could also be in line for future sales milestone payments. (See BioWorld Today, Feb 15, 2017.)
Amgen Inc., of Thousand Oaks, Calif., said it submitted a supplemental biologics license application (sBLA) to the FDA and an application for a variation to the marketing authorization to the EMA for Xgeva (denosumab). The submissions seek to expand the currently approved indication of the drug for the prevention of skeletal-related events (SREs) in solid tumors to include patients with multiple myeloma. The sBLA is based on efficacy and safety data from the pivotal phase III '482 study, which demonstrated that Xgeva is noninferior to zoledronic acid in delaying the time to first on-study SRE in patients with multiple myeloma (p=0.01). The secondary endpoints of superiority in delaying time to first SRE and delaying time to first-and-subsequent SRE were not met in that study.
Aviragen Therapeutics Inc., of Atlanta, said it plans to explore a wide range of strategic alternatives that include a business combination or strategic merger, in-licensing clinical-stage programs, an acquisition or other transaction that would complement the company's current pipeline and could maximize both near- and long-term shareholder value. The company, which is focused on the discovery and development of the next generation of direct-acting antivirals to treat infections that have limited therapeutic options, said it will reduce its headcount by approximately 25 percent and has retained Stifel, Nicolaus & Co. Inc. to serve as its financial advisor.
Benitec Biopharma Ltd., of Sydney, said preclinical efficacy results of the oculopharyngeal muscular dystrophy (OPMD) program have been published in Nature Communications. OPMD, a rare progressive muscle-wasting disease caused by a mutation in the poly(A)-binding protein nuclear 1 (PABPN1) gene, is characterized by eyelid drooping, swallowing difficulties and proximal limb weakness. The key results from the studies demonstrate that a DNA-directed RNA interference approach to silence and replace the mutant PABPN1 protein results in the correction of the muscular dystrophy and of key clinical features of OPMD, including a progressive atrophy and muscle weakness associated with nuclear aggregates of insoluble PABPN1. Those data were generated in the A17 mouse model that expresses the mutant PABPN1 gene and mimics most of the features of human OPMD patients.
Cannabics Pharmaceuticals Inc., of Tel Aviv, Israel, received the final report of the research held in the Technion Israel Institute of Technology, in which the antitumor activity of cannabinoids was reflected in several types of cancer (breast, ovarian, colon, pancreatic, gastric, glioblastoma). The results obtained using high-throughput screening technology indicated that the company's cannabinoid compounds caused apoptosis in all cancer types mentioned with no effect on healthy normal cells, Cannabics said.
Celgene Corp., of Summit, N.J., received a paragraph IV notice letter advising that Teva Pharmaceuticals USA Inc., an arm of Teva Pharmaceutical Industries Ltd., of Petah Tikva, Israel, submitted an abbreviated NDA to the FDA seeking authorization to manufacture and market a generic version of the multiple myeloma drug Pomalyst (pomalidomide) 1 mg, 2 mg, 3 mg and 4 mg in the U.S. Celgene said it intends to vigorously defend its extensive intellectual property rights related to Pomalyst.
Contravir Pharmaceuticals Inc., of Edison, N.J., said new studies of its hepatitis B virus-optimized cyclophilin inhibitor CRV431 show that it blocks the interaction between hepatitis B surface antigen (HBsAg), a key HBV protein, and cyclophilin A, an important cellular protein.
Dipharma SA, of Chiasso, Switzerland, disclosed the successful development of a new, fast-dissolving formulation of carglumic acid tablets stable at room temperature. Carglumic acid is used in the management of rare, life-threatening inborn metabolic disorders affecting the urea cycle. Dipharma also filed a patent application claiming new fast-dissolving and stable tablet formulations of carglumic acid, together with the proprietary technology developed to improve the product stability, without modifying the pharmaceutical form familiar to patients.
Evoke Pharma Inc., of Solana Beach, Calif., said it recently completed a type A meeting with the FDA to finalize the design of the pivotal comparative exposure pharmacokinetic trial and to reach agreement on additional aspects of the chemistry, manufacturing and controls section of the NDA for Gimoti, the company's nasal delivery formulation of metoclopramide for the relief of symptoms associated with acute and recurrent diabetic gastroparesis in adult women. During a pre-NDA meeting announced in December 2016, the FDA agreed with Evoke that a comparative exposure trial to demonstrate the bioequivalence of Gimoti in healthy volunteers could serve as the basis for a 505(b)(2) NDA submission for Gimoti. The FDA recommended that Evoke submit the trial protocol for review prior to initiating the study, which Evoke provided in early March 2017. The type A meeting was granted to allow comment and discussion with the FDA regarding the structure, population and overall design of the trial. After discussing the protocol design with FDA, Evoke has agreed with the agency's comments and plans to incorporate the recommendations in the final protocol.
Fit Biotech Oy, of Tampere, Finland, said it met a major research milestone with its new gene delivery vector, gtGTU. Preclinical research in cancer models demonstrated proof-of-concept tumor growth inhibition and improved survival for the new vector platform with two passive immunotherapy gene-based medicines. Fit Biotech has filed a patent application for the new vector platform. A scientific publication is currently being prepared, the company said.
Kadmon Holdings Inc., of New York, submitted its second abbreviated NDA (ANDA) to the FDA for KD034, the company's trientine hydrochloride formulation for the treatment of Wilson's disease, a rare genetic liver disorder, for patients who are intolerant of penicillamine. The company also submitted an ANDA for a bottled form of trientine hydrochloride in December 2016. The second ANDA is for Kadmon's generic version of trientine hydrochloride in blister packaging that offers room temperature storage, which the company said it believes has the potential to address shortcomings of currently available trientine hydrochloride formulations.
Kite Pharma Inc., of Santa Monica, Calif., highlighted a publication in the latest issue of Nature Methods that describes preclinical findings demonstrating that a serum-free, 3-dimensional cell culture technology, known as the Artificial Thymic Organoid (ATO) cell culture system, recapitulates T-cell differentiation. The findings support the potential of ATO technology to generate off-the-shelf engineered T cells to treat cancer and other diseases, Kite said, and the company holds an exclusive license to the ATO cell culture technology from the University of California, Los Angeles. The ATO cell culture system mimics the function of the human thymus to allow differentiation of fully functioning T cells from hematopoietic stem cells.
Redhill Biopharma Ltd., of Tel-Aviv, Israel, gained FDA orphan status for Yeliva (ABC294640) for the treatment of cholangiocarcinoma. The company plans to start a phase IIa study of the oral sphingosine kinase-2 inhibitor in patients with advanced, unresectable, intrahepatic and extrahepatic cholangiocarcinoma in the third quarter. Meanwhile, multiple other studies of Yeliva are ongoing, including a phase II study for the treatment of advanced hepatocellular carcinoma, a phase Ib/II study of the candidate for the treatment of refractory or relapsed multiple myeloma, and a phase I/II study in patients with refractory/relapsed diffuse large B-cell lymphoma as well as Kaposi sarcoma. A phase Ib study to evaluate the candidate as a radioprotectant for prevention of mucositis in head and neck cancer patients undergoing therapeutic radiotherapy is planned for initiation in the third quarter and a phase II study to evaluate the efficacy of Yeliva in patients with moderate to severe ulcerative colitis is planned to be initiated in the second half of 2017.
Sigmoid Pharma Ltd., of Dublin, agreed to work with Freiburg, Germany-based Dr. Falk Pharma GmbH to advance Sigmoid's SmPill cyclosporine franchise for ulcerative colitis, graft-vs.-host disease and other gastrointestinal diseases. The terms of the agreement include an up-front equity investment in Sigmoid, development funding, milestone payments as well as tiered double-digit royalties for the future development and commercialization of Cycol, Allocol and related products in Europe. Sigmoid retains rights to the programs outside of Europe and Canada. The value of the up-front, development funding and milestone payments were not disclosed.
Uniqure NV, of Lexington, Mass., highlighted the online publication in Gene Therapy of data demonstrating widespread transduction in the central nervous system following direct injection of its AAV5 vector in a large animal model. The company has exclusive, worldwide rights to AAV5 for use in therapeutic products delivered to the brain or liver. It said the new data will help guide the clinical development of its gene therapy candidate AMT-130, which consists of an AAV5 vector carrying an artificial micro-RNA that silences the huntingtin gene for the treatment of Huntington's disease. An investigational new drug application for AMT-130 is expected to be filed with the FDA in 2018.