Acucela Inc., of Seattle, said it plans to convert Acucela Japan Kabushiki Kaisha, which was established as a Japanese subsidiary in December last year, into a holding company that controls Acucela North America Inc., which will succeed to the business of the company, in order to relocate the head office functions to Japan. The change will be effected through a triangular merger with one share of common stock of the Japan Holding company distributed in exchange for each share of common stock of the company, and the Japan holding company will apply for listing of shares of common stock on the Tokyo Stock Exchange.
Scientists from the Japan Adult Leukemia Study Group have identified a recurrent gene fusion that occurred specifically in adolescent and young adult acute lymphoblastic leukemia (AYA-ALL) patients ages 15 to 39. Most ALL cases in the AYA age group lack the "Philadelphia chromosome" Bcr-Abl fusion and other known drivers of ALL, and so the team set out to identify other drivers. Screening for fusion genes uncovered a fusion of DUX4 with other genes that was present in about a quarter of AYA-ALL cases, but absent in either pediatric or adult ALL cases. The authors concluded "that DUX4 can become an oncogenic driver as a result of somatic chromosomal rearrangements and that AYA-ALL may be a clinical entity distinct from ALL at other ages." They published their results in the March 28, 2016, online issue of Nature Genetics.
Array Biopharma Inc., of Boulder, Colo., and Asahi Kasei Pharma Corp., of Tokyo, said they agreed to develop and commercialize select tropomyosin receptor kinase A (TrkA) inhibitors, including Array-invented ARRY-954, for pain, inflammation and other noncancer indications. TrkA is a high-affinity receptor for nerve growth factor and is widely expressed on peripheral pain-sensing neurons. Array retains full rights to cancer indications for all compounds, excluding those being development by Asahi Kasei. Under the terms, Array will get an up-front payment of $12 million and will be entitled to up to $64 million in development and commercialization milestones, as well as double-digit royalties. In exchange, Asahi Kasei will gain exclusive rights to the products in Japan, Korea, Taiwan and China.
Astrazeneca plc, of London, said Japan regulators approved Tagrisso (osimertinib) for use in patients with EGFR T790M mutation-positive metastatic non-small-cell lung cancer. Approval was based on data from two phase III studies – AURA extension and AURA2 – demonstrating objective response rates of 61.3 percent and 70.9 percent, respectively. Tagrisso previously gained approval in the U.S. and Europe. (See BioWorld Today, Nov. 16, 2015, and Dec. 21, 2015.)
India's Central Drugs Standard Control Organization proposed revisions to its 2012 guidelines for biosimilars that could allow biosimilar competition as soon as an innovator biologic is approved and marketed in Europe, the U.S. or other countries participating in the International Council for Harmonisation (ICH). Under the 2012 guidelines, "similar biologics" can reference innovator drugs that have been approved using a complete data package in India. If the innovator hasn't been approved in India, a biosimilar may reference a biologic that's been licensed and widely marketed for at least four years in a country with a well-established regulatory framework. In public health emergencies, the four-year period can be reduced or waived. The proposed guidelines do away with the four-year wait and clarify that if the innovator hasn't been approved in India, it must be approved and marketed in an ICH country. The proposed guidelines provide no exclusivity for the innovator.
Dr. Reddy's Laboratories Ltd., of Hyderabad, India, said it entered a licensing agreement with Eisai Co. Ltd., of Woodcliff Lake, N.J., in which Dr. Reddy's will gain exclusive worldwide development and commercialization rights, excluding Japan and Asia, for Eisai's cancer candidate, E7777, a fusion protein combining the interleukin-2 binding domain with diphtheria toxin fragments that is in phase II testing in cutaneous T-cell lymphoma. Eisai will be responsible for the development and marketing of the drug in Japan and Asia, while Dr. Reddy's holds the option to develop and market the agent in India. In exchange for those rights, Eisai will receive milestone payments in line with obtaining marketing approval and the achievement of agreed-upon sales targets.
India's Drug Controller General sent out a memo this week ordering that the backlog of pending clinical trial applications and drug and device approvals be cleared within three weeks. The memo to the subject expert committees at the Central Drugs Standards Control Organization provides instructions on expediting the reviews. The goal is to adhere to review timelines and reach a "zero level pendency," according to the memo.
Glaxosmithkline plc, of London, said the Japanese Ministry of Health, Labour and Welfare approved Malarone (atovaquone-proguanil hydrochloride) pediatric combination tablets for the treatment of malaria.
Republican leadership of the House Energy and Commerce Committee excoriated the FDA for its foot-dragging in the investigation of intentionally contaminated heparin from China. In a letter this week to FDA Commissioner Robert Califf, the lawmakers noted that it's been more than seven years since the investigation opened into the 2007-08 contamination that killed more than 80 patients and sickened many more, and yet the people responsible and the methods they used to get the contaminated product into the international supply have yet to be identified. The letter pointed out numerous shortcomings in the FDA's investigation, adding that the extensive delay raises serious questions about the agency's effectiveness in handling the issue. (See BioWorld Today, March 3, 2008, and March 18, 2008.)
Janssen Pharmaceutical Co. Ltd., of Tokyo, a unit of Johnson & Johnson, said Japanese regulators approved Bruton's tyrosine kinase inhibitor Imbruvica (ibrutinib) in relapsed or refractory chronic lymphocytic leukemia, including small lymphocytic leukemia.
Meiji Seika Pharma Co. Ltd., of Tokyo, said antipsychotic agent asenapine maleate sublingual tablets 5 mg were approved in Japan for use in schizophrenia patients.
Mesoblast Ltd., of Melbourne, Australia, said results from its phase IIa trial in patients with post-traumatic knee injury to the anterior cruciate ligament (ACL) showed that a single intra-articular injection of its mesenchymal precursor cell (MPC) candidate, MPC-75-IA, resulted in improvement in pain, function, cartilage thickness and joint structure over 24 months. The study, which randomized 17 patients, who had undergone ACL knee reconstruction surgery four to six week earlier, to receive either a single intra-articular injection of 75 million allogeneic MPCs plus hyaluronic acid (HA) or HA alone. Pain, function and quality of life parameters were measured using the composite of Knee Injury and Osteoarthritis Outcomes Scores and the Short Form Health Survey. Primary and secondary endpoints were met. Mesoblast said it is now planning a larger phase II/III trial to confirm those benefits.
Opthea Ltd., of Melbourne, Australia, completed enrollment in an ongoing phase I dose-escalation trial of OPT-302 to treat wet age-related macular degeneration (AMD) under an investigational new drug program with the FDA. The first-in-human, open-label study is expected to enroll 20 patients to evaluate the safety and clinical activity of intravitreal injections of OPT-302 alone or in combination with standard-of-care Lucentis (ranibizumab, Roche AG) in patients with wet AMD. Opthea said, to date, OPT-302 administered at doses of 0.3 mg or 1 mg in combination with Lucentis was well tolerated and showed a promising safety profile in treatment-naïve and previously treated wet AMD patients.
Pharmamar SA, of Madrid, Spain, reported top-line results from its phase III study, ADMYRE, showing that Aplidin (plitidepsin) in combination with dexamethasone produced a statistically significant 35 percent reduction in the risk of progression or death vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma, meeting the primary endpoint (p=0.0054). The pivotal study enrolled 255 patients. Pharmamar previously licensed rights to Aplidin, which targets eEF1A2 in tumor cells, to Specialised Therapeutics Asia Pte Ltd., of Singapore, covering seven Asian countries, Australia and New Zealand.
Portola Pharmaceuticals Inc., of South San Francisco, entered a clinical collaboration agreement with Daiichi Sankyo Co. Ltd., of Tokyo, to develop andexanet alfa as an antidote for edoxaban, Daiichi Sankyo's Factor Xa inhibitor, in Japan. Portola is developing andexanet alfa for patients treated with a direct or indirect Factor Xa inhibitor when reversal of anticoagulation is needed, such as for life-threatening or uncontrolled bleeding or emergency surgery and urgent procedures. Portola will receive an undisclosed up-front payment and is eligible to receive an additional milestone payment based on Japanese Ministry of Health, Labor and Welfare approval of andexanet alfa as an antidote for edoxaban. Daiichi Sankyo will provide technical support and fund all clinical studies of andexanet alfa with edoxaban in Japan. Daiichi Sankyo will receive no commercial or financial rights under this agreement.
Sanofi SA, of Paris, said it received Japanese approval for anti-epileptic drug Sabril Powder (vigabatrin) 500 mg. Developed jointly in Japan with Alfresa Pharma Corp., of Osaka, Sabril is indicated for infantile spasm. In separate news, Japan regulators also approved Sanofi's primaquine tablets 15 mg for the treatment of tertian malaria and ovale malaria.
Shionogi & Co. Ltd., of Osaka, Japan, said it submitted a new drug application in Japan and the U.S. for a once-daily, oral, 0.2-mg tablet of naldemedine, a peripherally acting mu-opioid receptor antagonist, for the treatment of opioid-induced constipation (OIC). In Japan, the proposed indication is for OIC in adults and, in the U.S., the proposed indication is for OIC in adults with chronic noncancer pain.
Skyepharma plc, of London, said partner Mundipharma International Corp. Ltd., of Singapore, received confirmation that its marketing authorization application for a breath-actuated version of flutiform was accepted for review in Europe. Mundipharma is seeking approval for treating asthma in adults and adolescents where the use of a combination product (inhaled corticosteroid/long-acting beta2 agonist) is appropriate.
Starpharma Holdings Ltd., of Melbourne, Australia, reported further efficacy results for itsDEP cabazitaxel in a human breast cancer model. It was compared with Jevtana in a human breast cancer preclinical model (xenograft). DEP cabazitaxel significantly outperformed Jevtana with respect to both level and duration of tumor regression (anticancer activity). Within four weeks of dosing, 100 percent of mice treated with Starpharma's DEP cabazitaxel were tumor-free and remained so for the duration of the extended study (150 days). In contrast, the Jevtana treated group exhibited significant tumor regrowth from day 60 onwards.
Sun Pharmaceutical Industries Ltd., of Mumbai, said it acquired 14 established prescription brands from Novartis AG, of Basel, Switzerland, in Japan for a cash consideration of $293 million. The brands have combined annualized revenues of about $160 million and address medical conditions across several therapeutic areas.
Taiho Pharmaceutical Co. Ltd., of Tokyo, reported results from its phase III TERRA study testing the oral combination cancer drug TAS-102 (trifluridine/tipiracil; branded Lonsurf in Japan and the U.S.) in Asian patients with refractory metastatic colorectal cancer (mCRC). The TERRA study met its primary endpoint of demonstrating improvement in overall survival in patients with refractory mCRC whose disease had progressed after approved standard therapies. TAS-102 also appeared to be generally well tolerated and its toxicities were consistent with what was previously reported. Taiho said it is preparing for regulatory submissions in Asian countries.
Takeda Pharmaceuticals Co. Ltd., of Osaka, Japan, said its U.S. subsidiary inked a multiyear research partnerships with the University of Chicago and the Icahn School of Medicine at Mount Sinai in New York for increased study in inflammatory bowel disease (IBD) research and care. During the three-year partnership, the University of Chicago will work to establish a patient-physician digital platform that communicates real-time disease status, collates environmental, molecular, genetic and microbiome factors for each patient and creates a system for identifying personalized IBD therapy. Mount Sinai will focus on immunology in IBD, including discovering novel paradigms of lymphocytic homing to the colon, identifying the effect of the microbiome on homing to the colon and exploring therapeutic cell-based approaches to suppress intestinal inflammation. In other news, Takeda and Valby, Denmark-based H. Lundbeck A/S got a complete response letter from the FDA regarding a supplemental new drug application in which they sought permission to include new data in the clinical trials section of the U.S. label of Brintellix (vortioxetine) for treating certain aspects of cognitive dysfunction in adults with major depressive disorder (MDD). The FDA approved Brintellix on Sept. 30, 2013, for the treatment of MDD in adults. In the past, the FDA has considered cognitive dysfunction in MDD as a "pseudospecific target" that couldn't be addressed separately from MDD, according to Cortellis Regulatory Intelligence. In a joint statement, the companies said that they "look forward to reviewing the contents of the letter with the FDA to determine the appropriate path forward."
Scientists from the University of California at Davis and the Chinese Guangzhou Institutes of Biomedicine and Health have demonstrated that the retinoic acid receptor–related orphan receptor gamma (ROR-gamma) is overexpressed and amplified in metastatic tumors that are no longer sensitive to androgen blockers. Early stage prostate cancer is treatable through androgen receptor blockage, and becomes deadly when it develops resistance to that initial treatment. In their studies, the authors looked for nuclear receptors other than androgen receptors whose expression might be changed in metastatic prostate cancer. They showed that ROR-gamma is such a receptor, and that its expression drove the expression of androgen receptors. Inhibiting ROR-gamma blocked androgen receptor expression and sensitized cells to the androgen receptor blocker Xtandi (enzalutamide, Medivation Inc.). The authors wrote that "taken together, these results establish ROR-gamma as a key player in [castration-resistant prostate cancer] by acting upstream of [androgen receptor] and as a potential therapeutic target for advanced [prostate cancer]. Their work appeared in the March 28, 2016, online issue of Nature Medicine.
Vedanta Biosciences Inc., of Boston, disclosed a license agreement with Riken Brain Science Institute in Wako, Japan, the University of Tokyo and Azabu University for technology developed by Riken that has potential clinical applications in infectious disease, vaccine design and immuno-oncology, the company said. Vedanta also received a second patent issuance in Japan for key intellectual property. Under the terms of the agreement, potential pharmaceutical candidates involving bacterial strains that activate immune cells in the human gut called Th17 cells will be investigated. Th17 cells are a specialized group of immune cells that may help protect the body against infectious pathogens and are also a potential target in the treatment of cancer, the company said. Further terms were not disclosed.