Cellular Biomedicine Group Inc., of Shanghai, reported results from an ongoing phase IIa trial evaluating the safety, feasibility and antitumor activity of its acquired chimeric antigen receptor-modified T-cell (CAR-T) immunotherapy (CBM-CD20.1) targeting CD20 for the treatment of patients with advanced B-cell non-Hodgkin lymphoma (NHL). A total of 10 patients were treated with CBM-CD20.1 (seven patients with diffuse large B-cell lymphoma (DLBCL) and three patients with other types of NHL). The results showed the immunotherapy was safe, well tolerated and efficacious in the treatment of patients with advanced NHL. Of the 10 patients with evaluable clinical outcome, the overall disease control rate (DCR) was 100 percent. Of the 10 NHL patients, eight showed a response (five complete remissions [CRs] and three partial remissions [PRs]) and two had stable diseases. Three of five CR patients had clinical durable responses for more than five months (and ongoing), and two of three PR patients achieved responses longer than six months (and ongoing). Of the seven DLBCL patients, the overall response rate is 85.7 percent (three CRs and three PRs).
Charleston Laboratories Inc., of Jupiter, Fla., and Daiichi Sankyo Co. Ltd., of Tokyo., said a third phase III trial with CL-108, an opioid-containing formulation, met its primary endpoints. CL-108 is a bilayered tablet containing 7.5 mg of hydrocodone and 325 mg of acetaminophen formulated with 12.5 mg of rapid-release promethazine. It is being developed as a treatment for moderate to severe pain and for the prevention of opioid-induced nausea and vomiting (OINV). The recently completed experiment was a randomized, double-blind, placebo- and active-controlled study in more than 550 patients in the U.S. who experienced moderate to severe pain after bunionectomy surgery. Results demonstrated significant pain relief and prevention of OINV by CL-108 (both p<0.001), the companies said.
Gilead Sciences Inc., of Foster City, Calif., and Wuxi Pharmatech Inc., of Shanghai, said they entered a strategic partnership to conduct analytical and stability studies of small-molecule new chemical entities to support global marketing applications and commercial products. Under the agreement, Wuxi will equip and operate a dedicated, fully cGMP-compliant analytical testing facility in Shanghai to provide analytical method development, transfer and validation for investigational new drug and new drug applications, commercial API and drug product testing and other services.
Hutchison China Meditech Ltd., of Hong Kong, said its Hutchison Medipharma Ltd. R&D subsidiary completed its phase I study of HMPL 523, a selective small-molecule inhibitor targeting spleen tyrosine kinase, or SYK, a key component in B-cell receptor signaling. The dose-escalating study was designed to assess the safety, tolerability and pharmacokinetics of both single and repeat doses of HMPL 523 in healthy volunteers in Australia. No material off-target toxicities such as hypertension and severe diarrhea were observed, and HMPL 523 exhibited a linear pharmacokinetic profile and a dose-dependent suppression of B-cell activation, the company said. The study tested four dose cohorts, from 200-mg multiple dose through to 400-mg multiple dose. At 400 mg daily, HMPL 523 drug exposures are believed to be well above the predicted efficacious dose level.
Intercept Pharmaceuticals Inc., of New York, said results of a 72-week, phase II, dose-ranging trial of FXR agonist obeticholic acid (OCA) in patients with nonalcoholic steatohepatitis (NASH) in Japan, showed that, in the intent-to-treat population, treatment had a dose-dependent improvement over placebo but fell short of statistical significance (p = 0.053). The 40-mg OCA dose group, however, achieved statistical significance on the primary endpoint compared to placebo (p = 0.0496). Dose-dependent trends not reaching statistical significance were also observed for several other pre-specified histologic endpoints, including the proportion of patients with steatosis and inflammation improvement, ballooning resolution and NASH resolution. No difference was seen in fibrosis improvement in the OCA groups compared to placebo. The trial was conducted by Intercept's collaborator, Sumitomo Dainippon Pharma Co., of Osaka, Japan. RBC Capital Markets analyst Michael Yee noted that the study had risk "because it was more of an exploratory study and much smaller than the prior FLINT study." FLINT data reported during 2014 showed the phase IIb trial met its endpoints in NASH. Intercept launched a phase III study, dubbed REGENERATE, earlier this year. Shares of Intercept (NASDAQ:ICPT) fell $3.51 to close Wednesday at $164.13 (See BioWorld Today, Jan. 10, 2014, Aug. 13, 2014, and May 20, 2015.)
Invion Ltd., of Brisbane, Australia, said it completed enrollment in its phase II study of INV102 (nadolol) in patients with mild asthma. The study, NIMA, was funded by the NIH and randomized 66 subjects. The last dose will be administered by the end of April 2016, followed by reporting of safety and efficacy data, which will be assessed by impact on nonspecific airway hyper-responsiveness after six months of therapy. INV102 is a beta adrenergic biased ligand targeted to reverse mucous metaplasia in the airway epithelium to treat chronic inflammatory airway diseases.
Living Cell Technologies Ltd., of Auckland, New Zealand, said the four patients who took part in its phase I/IIa study of Ntcell to treat Parkinson's disease reached 42 weeks post-implant without disease progression or safety concerns. Data from ongoing monitoring of the patients were measured by validated neurological rating scales and questionnaires, including the Unified Parkinson's Disease Rating Scale, the Unified Dyskinesia Rating Scale and the Parkinson's Disease Quality of Life Questionnaire. Combined, the rating scales suggested clinically and statistically significant improvement in neurological scores from baseline, according to the company.
Mesoblast Ltd., a Melbourne, Australia-based regenerative medicine company, has filed to sell about 5.7 million American depositary shares (ADS), representing about 28.7 million ordinary shares, at a price of $12.10 per ADS (assuming an exchange rate of US$0.7103 per Australian dollar) in the company's U.S. market debut on Nasdaq. The offering could gross $69.5 million. The company expects to list under the symbol MESO and plans to use proceeds primarily to support commercial manufacturing requirements for its most advanced product candidates in a variety of indications through development and manufacturing. (See BioWorld Insight, Jan. 21, 2014.)
Prima Biomed Ltd., of Sydney, gained approval from Belgium's Federal Agency for Medicines and Health Products to move ahead with a randomized, double-blind, placebo-controlled phase IIb study of IMP321, a natural antigen-presenting cell activator and T-cell immunostimulatory factor based on the immune checkpoint LAG-3, in metastatic breast cancer. Patients in the study, called the active immunotherapy paclitaxel trial, or AIPAC, will be administered subcutaneous doses of IMP321 on days two and 16 of a weekly regimen of paclitaxel, the day after their paclitaxel infusion. AIPAC will aim to initially recruit 15 patients for a smaller safety run-in in three different countries, testing in combination with paclitaxel the safety of IMP321 in doses up to 30 mg per dose, which has previously been shown to be safe when tested as a monotherapy and is significantly higher than the maximum 6.25-mg dose from the company's phase I trial in metastatic breast cancer. Prima expects to report data in the study in the second half of 2016. In other news, Prima said it raised A$2 million (US$1.42 million) via an equity placement at A$0.05 per ordinary share to a leading Australian institutional investor. The proceeds will be used to fund the company's IMP321 clinical trial program and provide additional working capital that will fund the company's operations into 2017.
Probiogen AG, of Berlin, and Bio Farma, of Bandung, West Java, Indonesia, signed an agreement for the development of a biosimilar trastuzumab for cancer treatment. Under the terms of the agreement, Probiogen will develop a manufacturing process based on a specifically designed recombinant CHO-cell line, conduct engineering runs and the industrial scale-up. The turnkey process, including state-of-the-art analytics, will then be transferred to Indonesia to enable local market production.
Seattle Genetics Inc., of Bothell, Wash., and Takeda Pharmaceutical Co. Ltd., of Osaka, Japan, said they completed target patient enrollment in the phase III ECHELON-1 trial, evaluating Adcetris (brentuximab vedotin) as part of a front-line combination chemotherapy regimen in patients with previously untreated advanced classical Hodgkin lymphoma (HL). Patients in the trial were randomized to receive either ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine), a recognized standard of care for front-line HL, or a combination consisting of Adcetris+AVD, which removes bleomycin from the regimen. The trial has enrolled about 1,300 patients, although it remains open at select sites to complete enrollment of about 20 patients in an additional cohort to fulfill an ex-U.S. regulatory commitment related to measurement of drug levels during treatment. The companies said that continued enrollment will not affect the expected timing of data readout from the trial in the 2017 to 2018 timeframe, based on anticipated event rates. The primary endpoint is modified progression-free survival per independent review facility assessment using the Cheson 2007 revised response criteria for malignant lymphoma. Secondary endpoints include overall survival, complete remission and safety. The trial is being conducted in North America, Europe, South America, Australia, Asia and Africa.
Serenus Biotherapeutics Corp., of Dublin and Johannesburg, struck a deal with South Korea's Hanmi Pharmaceutical Co. Ltd. to supply Amosartan (amlodipine camsylate/losartan potassium), Hanmi's combination therapy for the treatment of hypertension, to patients in Africa. Cardiovascular diseases are the number one cause of death in adults older than 30 years of age in sub-Saharan Africa, according to the World Health Organization. Serenus specializes in late-stage drug development, in-licensing, registering and commercializing drugs and devices approved in the U.S., Europe and Japan to address unmet medical needs in the sub-Saharan African market.
Wave Life Sciences Pte. Ltd., of Singapore, set terms for an IPO in which it plans to sell 5 million shares, priced between $15 and $17 each. At its midpoint, the offering would gross $80 million. The company, which expects to list under the symbol WVE, plans to use proceeds to fund additional preclinical studies and phase I trials for its HTT SNP-1 program in Huntington's disease; the selection of a lead product candidate and additional preclinical studies and phase I trials for its HTT SNP-2 program, also in Huntington's disease; additional preclinical studies and phase I trials for its Duchenne muscular dystrophy exon 51 program; and the selection of a lead product candidate and additional preclinical studies and phase I trials for its IBD SMAD7 program in inflammatory bowel disease. (See BioWorld Today, Feb. 3, 2015.)