Monday, December 10, 2018
Sermonix announces FDA acceptance of IND application for lasofoxifene
Sermonix Pharmaceuticals announced that the U.S. Food and Drug Administration accepted the company’s Investigational New Drug application, indicating that Sermonix may proceed directly to a Phase 2 clinical study in the personalized medicine arena involving its lead investigational drug, lasofoxifene. The open-label, randomized, multi-center study is expected to begin enrollment in early 2019 and will evaluate the activity of oral lasofoxifene versus intramuscular fulvestrant for the treatment of postmenopausal women with locally advanced or metastatic estrogen receptor-positive (ER+)/HER2- breast cancer with an ESR1 mutation. A large amount of clinical data from earlier non-oncology development, along with new, compelling preclinical data have enabled Sermonix to commence directly into the Phase 2 study. The study will include postmenopausal women with ESR1 mutations, identified using a liquid biopsy clinical trial assay, who have progressed after aromatase inhibitor and CDK 4/6 inhibitor therapy. ESR1 mutations occur in up to 40 percent of women with metastatic breast cancer and may confer a worse prognosis and poor response to currently available endocrine treatments. Lasofoxifene is an investigational, nonsteroidal selective estrogen receptor modulator, which Sermonix licensed from Ligand Pharmaceuticals.
https://thefly.com/landingPageNews.php?id=2834673
Merck KGaA Gets FDA Orphan Drug Tag for Biliary Tract Cancer Immunotherapy
- FDA grants M7824, an investigational bifunctional immunotherapy, orphan drug designation in biliary tract cancer
- First regulatory designation for M7824 following recent presentation of first clinical data in BTC
- BTC is a group of rare, aggressive gastrointestinal cancers associated with limited treatment options and poor outcomes
Merck KGaA, Darmstadt, Germany, a leading science and technology company, which operates its healthcare business in the U.S. and Canada as EMD Serono, today announced that the US Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to M7824, the first regulatory designation for the bifunctional immunotherapy, for the treatment of biliary tract cancer (BTC). The FDA orphan drug designation follows the recent presentation of the first clinical data for M7824 in BTC at the European Society of Medical Oncology (ESMO) congress in October. M7824 is an investigational bifunctional immunotherapy designed to combine co-localized blocking of the transforming growth factor-β and anti-PD-L1 immune escape mechanisms.
BTC is a collective term for a group of rare and aggressive gastrointestinal cancers, including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder carcinoma (GBC).[1] Approximately 16,000 cases of BTC are estimated to occur every year in the US and collectively these cancers present late in the majority of patients. [1],[2] Treatment options are limited and the median survival rate in the advanced setting is less than one year, objective tumor response with commonly used chemotherapy is typically less than 10% with short duration of response. [1],[3],[5]
“Biliary tract cancer is a rare, notoriously hard-to-treat tumor where existing treatment approaches, such as surgery or chemotherapy, are either not viable or simply don’t deliver acceptable patient outcomes,” said Luciano Rossetti, Head of Global Research & Development at the Biopharma business of Merck KGaA, Darmstadt, Germany. “As the first regulatory designation for M7824, Merck KGaA, Darmstadt, Germany is excited about the potential of this new class of immunotherapy in a number of challenging cancers and settings.”
The first clinical data for M7824 in BTC, presented at the ESMO congress in October, demonstrated clinical activity in Asian patients who had progressed after platinum-based first-line treatment. The ORR among the total of 30 patients was 20%, as assessed by IRC, and responses were observed across PD-L1 levels with a duration of response ranging from 8.3 months to 13.9+ months. Grade 3 or higher TRAEs were experienced by 10 patients (33.3%) and the most common Grade 3 TRAEs were rash (10%) and lipase increase (10%).
Bristol, Vedanta to Evaluate Combo in Advanced, Metastatic Cancers
Bristol-Myers Squibb Company (NYSE: BMY) and Vedanta Biosciences today announced a clinical trial collaboration to evaluate Bristol-Myers Squibb’s programmed death-1 (PD-1) immune checkpoint inhibitor Opdivo(nivolumab) in combination with Vedanta Biosciences’ VE800, a rationally-defined human bacterial consortium, in patients with advanced or metastatic cancers.
In a range of preclinical models of cancer, including those sensitive and resistant to checkpoint inhibition, VE800 was shown to induce CD8+ T cells, potentiate the immune system’s attack of tumor cells, and significantly amplify the effects of anti-PD-1 therapy. These models support clinical research to explore whether modulating the microbiome with VE800 has the potential to broaden the efficacy of checkpoint inhibitors.
“Our lead, microbiome-based immuno-oncology candidate, VE800, is based on work conducted in collaboration with our co-founder, Dr. Kenya Honda, showing in preclinical models that certain gut-dwelling bacterial strains potentiate cytotoxic CD8+ T cells and enhance infiltration into tumors,” said Bernat Olle, Ph.D., Co-founder and Chief Executive Officer of Vedanta Biosciences. “Through this collaboration our goal is to determine whether VE800 in combination with Opdivo can improve outcomes for patients with advanced or metastatic cancers.”
“We are continuing to explore the novel mechanisms of new assets in combination with our oncology portfolio,” said Fouad Namouni, M.D., head of development, oncology, Bristol-Myers Squibb. “Vedanta Biosciences is a leading company focused on the characterization of immunomodulatory human gut commensals and the development of live bacterial products for the potential treatment of human diseases. Our collaboration with Vedanta Biosciences will allow us to gain a deeper understanding about the emerging microbiome landscape, its role in oncology, and the potential to improve outcomes for patients with advanced or metastatic cancer.”
“Checkpoint inhibitors, particularly PD-1 antibodies, have been a major advance in cancer therapy; however, a large proportion of patients either do not respond or have response of brief duration to those new therapies,” said Jeffrey Weber, M.D., Ph.D., Deputy Director, Laura and Isaac Perlmutter Cancer Center and Professor of Medicine, NYU Langone Health. “Alteration of the gut microbiome could play a significant role in enhancing the effectiveness of checkpoint inhibitors, and with increased understanding may also be used to select for patients who would benefit most from these immunotherapies.”
In conjunction with this collaboration, and subject to the completion of due diligence, the negotiation by the parties of definitive transaction agreements and the receipt by Bristol-Myers Squibb of all requisite approvals, Bristol-Myers Squibb currently intends to make an equity investment in Vedanta Biosciences. Vedanta Biosciences will maintain control of its VE800 program, including global R&D and commercial rights.
Novan announces results from Phase 2 SB206 trial
Novan announced full top line results from the company’s Phase 2 clinical trial to evaluate topical nitric oxide product candidate SB206 for the treatment of molluscum contagiosum, including results from the fourth cohort, SB206 12% once-daily. Results demonstrated a clear treatment effect on the complete clearance of all molluscum lesions at Week 12 for 12% once-daily SB206 gel, with signs of efficacy evident as early as Week 2. The safety and tolerability profiles for all treatment groups were favorable, with no serious adverse events reported. Preliminary top line results from the first three cohorts, 4%, 8% and 12% twice-daily, were announced in November. Novan conducted a 12-week, randomized, double-blind, vehicle-controlled, ascending dose Phase 2 trial to evaluate four treatment groups of 4%, 8% or 12% twice-daily or 12% once-daily, and vehicle as a treatment for molluscum. The primary endpoint was complete clearance of all molluscum lesions at Week 12. For the primary endpoint, 12% once-daily was the most effective dose with 42% and 38% complete clearance rates compared to 20% and 18% for vehicle, respectively. For the secondary endpoint of mean percent change from baseline molluscum lesion count at each visit, patients treated with 12% once-daily experienced 29%, 37%, 56% and 55% reductions in molluscum lesions at Week 2, 4, 8 and 12, respectively. The 12% once-daily treatment group had the lowest dropout rate out of all treatment groups, 9%, with 0 patients discontinuing treatment due to adverse event. With the full results from this Phase 2 trial now available, the company intends to request, by the end of December, an end-of-Phase 2 meeting with the FDA. This meeting would enable Novan and the FDA to agree on a Phase 3 development plan for molluscum with SB206 12% once-daily as the active treatment arm. Following a successful end-of-Phase 2 meeting with the FDA, the company plans to initiate a Phase 3 program of SB206 for molluscum in the first half of 2019 with top line results possible by the end of 2019 or early in 2020.
Tivity Health sees double digit accretion from Nutrisystem deal in 2020, beyond
In slides being presented on the conference call discussing the acquisition of Nutrisystem (NTRI) by Tivity Health (TVTY), Tivity says it has identified approximately $30M-$35M in annual cost synergies, anticipated to be fully achieved on a run rate basis by 2021. The company sees significant additional upside through revenue and other cost synergies and sees synergies phased in over three years. One-time costs to achieve the synergies are expected to be less than $30M and Tivity sees achieving double digit accretion in 2020 and beyond.
Marinus Pharmaceuticals announces results from two ganaxolone studies
Marinus Pharmaceuticals announced “positive” results from its Phase 2 clinical trials evaluating ganaxolone intravenous, or IV, and oral in women with postpartum depression, or PPD. Based on these results, the company is advancing both studies into the next phase of development to evaluate IV and oral dose regimens. There was a clear dose response relationship seen for three groups of patients receiving ganaxolone IV at median doses of 60, 90 and 140 microg/kg/h.The 140 microg/kg/h dose group demonstrated the most robust results, with a clinically meaningful 5.6-point reduction in Hamilton Rating Scale for Depression, or HAM-D17, compared to placebo at 48 hours that was durable through the last visit, day 34. These patients had a mean HAM-D17 reduction of 16.9 and 15.7 points from baseline at 60 hours and day 34, respectively. Overall, 75% of patients were responders, as defined as having a 50% reduction from baseline, at day 34 and 67% were responders at 60 hours. Additionally, 50% of patients achieved remission from depression, as determined by a HAM-D17 of 7, at day 34 and 33% achieved remission at 60 hours. Ganaxolone was safe and well-tolerated in all dose groups. Consistent with previous ganaxolone studies, the most common reported adverse events were sedation and dizziness. There were no serious adverse events reported, no discontinuations due to a treatment related adverse event and consistent with prior studies, there were no reports of syncope or loss of consciousness. The Clinical Global Impression of Improvement, or CGI-I, as well as the Edinburgh Postnatal Depression Survey, or EPDS, and Spielberger State-Trait Anxiety 6, or STAI-6, showed highly similar trends that were consistent with HAM-D17. Overall, 58 patients with PPD were randomized on a 1:1 basis to receive one of three ascending fixed IV 60-hour dose regimens of ganaxolone or placebo. No initial up titration was required and patients were down titrated over the final 12 hours of the 60-hour infusion. A bolus injection of ganaxolone prior to the 60-hour infusion was explored to test the safety and tolerability of a very short, high dose infusion. None of the dose groups were powered to generate statistical significance. Patients with a HAM-D17 score of 26 were considered for enrollment in the study. HAM-D17 measurements were conducted by a centralized rater and taken at various timepoints spanning from baseline to day 34. Enrollment is ongoing in the company’s oral study, a Phase 2 clinical trial to evaluate the safety, tolerability and efficacy of oral ganaxolone in women with PPD. Patients with a HAM-D17 score of 20 but less than 26 are being considered for enrollment in the study. Cohorts of patients enrolled in the initial open label phase of the study receive ascending dose regimens with oral ganaxolone. The efficacy endpoint is change from baseline in the HAM-D17 score. Patients in the most recent dose cohort who took oral ganaxolone for four weeks had a mean HAM-D17 reduction of 13.2 points 28 days from a baseline of 24.7 and a reduction of 15.7 points at day 36. This cohort is on-going and not all patients have reached day 28. As with IV, oral ganaxolone was generally safe and well-tolerated with no serious adverse events reported and no discontinuations due to treatment related adverse events. The company is advancing both the Magnolia and Amaryllis studies with data expected in the first half of 2019. The second part of the Magnolia Study will evaluate a short IV infusion followed by oral ganaxolone administration and the Amaryllis study will continue to optimize oral ganaxolone dosing.
Pfenex submits PF708 NDA to FDA
Pfenex (PFNX) announced the submission of its new drug application, or NDA, to the FDA seeking approval of PF708 for the treatment of osteoporosis. The application is submitted as a 505 NDA and references Eli Lilly’s (LLY) Forteo as the reference listed drug.
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