Beigene Ltd., of Beijing, announced dosing of the first patient in a pivotal trial of BGB-3111, the company's Bruton's tyrosine kinase inhibitor, in Chinese patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The primary endpoint of the single-arm, open-label, multicenter study is objective response rate, defined as achievement of either a partial response or complete response at any time on study drug. Secondary endpoints include progression-free survival, duration of response, time to response, safety and tolerability. BGB-3111 is also being evaluated in a pivotal phase II trial in Chinese patients with relapsed or refractory mantle cell lymphoma and a global phase III trial in comparison with Imbruvica (ibrutinib, Abbvie Inc. and Johnson & Johnson) for the treatment of patients with Waldenström's macroglobulinemia. In other news, Beigene and the Guangzhou Development District (GDD) said Beigene Hong Kong Co. Ltd., a wholly owned subsidiary of Beigene and GDD, and its affiliate, Guangzhou GET Technology Development Co. Ltd., have entered a definitive agreement to establish a state-of-the-art commercial-scale biologics manufacturing facility in Guangzhou, China. In the joint venture, Beigene Biologics Co. Ltd. will also provide funding for research and development of biologic drug candidates in China. Total direct investments are expected to be ¥2.2 billion (US$330 million). Under the terms of the agreement, the cash contributions to Beigene Biologics, the joint venture company, consist of ¥200 million from Beigene Hong Kong and a total of ¥1 billion from GET, including cash in an equity investment of the joint venture and a shareholder loan, which may be convertible into equity of the joint venture company. For additional funding, the manufacturing factory subsidiary of the joint venture company is expected to secure commercial loans of ¥1 billion.
Benitec Biopharma Ltd., of Sydney, said it issued an additional 29.3 million fully paid ordinary shares to Nant in accordance with an October 2016 share subscription agreement between Benitec and Nant Capital LLC. The issued shares, priced at A$0.1859 each, raised a total of A$5.45 million (US$4.13 million) for the company. As a result of the placement, Nant now holds 28.57 percent of the issued capital of Benitec. Proceeds will be used to support both the oncology collaboration between Benitec and Nantworks Inc., of Culver City, Calif., and the progression of Benitec's existing programs towards the clinic.
Duchesnay Inc., of Blainville, Quebec, acquired exclusive U.S. and Canadian rights to market and distribute Osphena (ospemifene) from Shionogi Inc., of Osaka, Japan. Osphena is an oral, non-hormonal prescription medication indicated for the treatment of moderate to severe dyspareunia (painful intercourse), a symptom of vulvar and vaginal atrophy due to menopause. The acquisition is effective immediately. Duchesnay intends to immediately begin detailing Osphena in the U.S. through its existing sales force. The company will also pursue regulatory approvals in Canada. Shionogi will continue to book sales for Osphena in the U.S. through March 31, 2021, and is expected to continue to supply Osphena to Duchesnay for eight years from the effective date of the transaction. Other terms were not disclosed.
Heptares Therapeutics Ltd., part of Sosei Group Corp., of Tokyo, said it cemented a drug discovery and licensing agreement with Daiichi Sankyo Co. Ltd., of Tokyo. Under the terms, Daiichi Sankyo has global rights to develop, manufacture and commercialize novel, small molecules discovered by Heptares, that are based on a single G protein-coupled receptor (GPCR) nominated by Daiichi Sankyo that plays a role in relieving pain. Heptares will receive $4 million up front, and is eligible for additional R&D and commercialization milestone payments. Heptares also will be eligible to receive royalties on net sales of products that result from the deal.
Hutchison China Meditech Ltd., of Hong Kong, presented data from the ongoing phase Ib/II trial of sulfatinib in patients with advanced neuroendocrine tumors (NETs) at the Conference of the European Neuroendocrine Tumor Society in Barcelona, Spain. Sulfatinib is an oral angio-immunokinase inhibitor that selectively targets VEGFR, FGFR and CSF-1R, three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion. The trial is assessing the efficacy and safety of sulfatinib monotherapy in patients with advanced grade 1 or 2 advanced NET with 81 patients (41 pancreatic NET and 40 extra-pancreatic NET) enrolled in seven clinical centers across China. As of Jan. 20, 13 patients had confirmed partial responses and 61 patients had stable disease, corresponding to an overall objective response rate of 16 percent (13/81), with 17.1 percent (7/41) in pancreatic NET and 15 percent (6/40) in extra-pancreatic NET, and an overall disease control rate of 91.4 percent. Median overall progression-free survival (PFS) has not been reached, but is estimated to be 16.6 months (95 percent CI: 13.4, 19.4) with longer median PFS in pancreatic NET estimated at 19.4 months and shorter median PFS in extra-pancreatic NET estimated at 13.4 months. Based on the promising efficacy data and tolerability in patients with advanced NETs, two randomized Phase III trials are ongoing.
Kitov Pharmaceuticals Holdings Ltd., of Tel Aviv, Israel, said it signed a license agreement for lead candidate KIT-302, in development to simultaneously treat pain caused by osteoarthritis and hypertension, for the territory of South Korea with Kuhnil Pharmaceutical Co. Ltd., of Seoul, South Korea. Kuhnil will gain the exclusive right and license to manufacture, distribute and sell KIT-302 in South Korea and will be responsible for seeking regulatory approval in the region. Under the terms, Kitov is entitled to receive milestone payments upon achievement of certain predefined regulatory milestones, as well as double-digit royalties on net sales. The initial term of the definitive agreement with Kuhnil is for 10 years from the date of first commercial sale and shall automatically renew for an additional one-year term. Commercial launch in South Korea is estimated to take place in 2019. Specific financial details were not disclosed.
Megafine Pharma Ltd., of Mumbai, India, was slapped with an FDA warning letter for using material sourced from a facility that had been placed on import alert in the manufacture of active pharmaceutical ingredients. The company also was cited for inadequate equipment maintenance, insufficient testing methods and data integrity problems. For instance, the company's quality assurance (QA) analysts were given blank controlled document forms that were already approved and signed. Additionally, FDA investigators found torn, partially complete QA-signed calibration records in the trash and observed QA staff shredding documents without recording the identity or the reason for shredding them.
Mesoblast Ltd., of Melbourne, Australia, said the FDA granted fast track status for the use of its cell therapy, MSC-100-IV, to achieve improved overall response rate in children with steroid-refractory acute graft-vs.-host disease. MSC-100-IV is described as a tier 1, intravenously delivered product candidate comprising 100 million mesenchymal stem cells per unit dose.
Opthea Ltd., of Melbourne, Australia, said it completed a type C meeting with the FDA aimed at obtaining regulatory guidance on the clinical development program and proposed phase IIb trial testing OPT-302, a VEGF-C/D trap therapy, in wet age-related macular degeneration. Opthea said the outcomes provide a path forward as it plans to launch the phase IIb trial this year. The company previously completed enrollment in phase IIa dose-expansion cohorts in a phase I/IIa trial, with data expected by the end of this month.
Regimmune Corp., of Tokyo, said phase IIa data published in Biology of Blood and Marrow Transplantation showed that RGI-2001, a liposomal formulation of a synthetic derivative of alpha-galactosylceramide, was safe and well-tolerated and expanded Foxp3+ regulatory T cells (Treg) mediated by the activation of invariant natural killer T cells in patients. RGI-2001 is in development to ameliorate graft-vs.-host disease (GVHD) after allogeneic hematopoietic cell transplantation. Tregs have been shown to have significant potential for treating GVHD, the company said. In studies by independent researchers, Tregs showed they could produce longer patient survival because they could suppress rejection without reducing an antitumor graft-vs.-leukemia effect. The phase IIa study enrolled 29 patients. A randomized study is being designed to further evaluate the impact of serial dosing of RGI-2001 on Treg biology and GVHD prevention.
Supernus Pharmaceuticals Inc., of Rockville, Md., said it entered a settlement agreement with Zydus Pharmaceutical (USA) Inc., of Pennington, N.J., and Cadila Healthcare Ltd., of Ahmedabad, India, involving the ongoing patent litigation regarding Zydus' abbreviated new drug application seeking approval to market generic versions of the company's Trokendi XR (extended-release topiramate) capsules. The settlement permits Zydus to begin selling a generic version of the drug on Jan. 1, 2023, or earlier under certain circumstances.
Synairgen plc, of Southampton, U.K., reported preclinical data from its LOXL2 (lysyl oxidase-like 2 enzyme) inhibitor program in idiopathic pulmonary fibrosis (IPF). Studies, conducted in collaboration with Pharmaxis Ltd., of Sydney, showed that those inhibitors could reduce cross-linking of collagen fibers in an in vitro model of IPF, resulting in a reduction in tissue stiffness of about 50 percent. Synairgen also reported that oral administration of one of the compounds significant inhibited cross-link formation, reduced fibrosis score and improved lung function in a preclinical model of lung fibrosis. Completion of toxicology studies will enable commencement of phase I trials in the second half of this year as planned.
Australia's Therapeutic Goods Administration (TGA) issued warnings Thursday about two counterfeit drugs that are being sold in the country via online sales. One drug, labeled as being made in China with the name "Placebo," contains the undeclared substance clenbuterol, a bronchodilator that the TGA considers a prescription drug. The other suspect product purports to be 100-mg tablets of tadalafil, a generic version of Cialis. The counterfeit tadalafil product contains two undeclared substances – sildenafil, a prescription drug used in Viagra, and metamizole, an analgesic that has been restricted in Australia due to links to agranulocytosis, a rare but sometimes fatal condition. The TGA is working with the Australian Border Force to stop future shipments of both unapproved drugs. Tablets found at the border will be seized and destroyed. Patients who have received the drugs are urged to stop taking them immediately.
Though macrophages can be manipulated into tumor fighters, their natural function is to further tumor growth. Researchers from the Chinese Zhejiang University have reported that in the case of liver cancer, they help cancer from the very first. By creating genetically defined tumor-initiating cells (TICs) and testing their effects on macrophages, the team was able to demonstrate that "macrophages play a decisive role in the survival of single TICs in vivo and provide a proof of principle for TIC elimination by targeting YAP" – the Yes-associated protein, which is activated by the Hippo pathway – "or M2 macrophages," the authors wrote. They reported their results in the Feb. 1, 2017, issue of Genes & Development.