The FDA granted AstraZeneca orphan status for olaparib, both for the treatment of fallopian tube cancer and for the treatment of primary peritoneal cancer.
Thursday, May 17, 2018
Novo Nordisk steps up interest in diabetes, Parkinson’s stem cell therapies
Novo Nordisk has talked up the progress of its Type 1 diabetes stem cell therapy program. With the diabetes project clearing milestones and moving to within a few years of the clinic, Novo is stepping up its interest in stem cell therapies more broadly.
The foundation for Novo’s stem cell therapy expansion was laid in collaboration with the University of California San Francisco (UCSF). Novo staffers are now working alongside academic collaborators at a GMP laboratory at UCSF. And the Danish drug developer has picked up the rights to technology to generate human embryonic stem cell lines.
In parallel, Novo has worked with Cornell University to address some of the barriers to the use of stem cells in the treatment of Type 1 diabetes. Specifically, the partners have created a device to protect beta cells from the host’s immune system.
With cell line work advancing at UCSF and the Cornell collaboration raising hopes a major barrier to curing diabetes can be overcome, Novo has set its sights on getting a diabetes candidate into human testing in the next few years. That makes Novo one of the bigger beasts in a race that also features Eli Lilly partner Sigilon Therapeutics and the well-financed Semma Therapeutics.
An effective stem cell treatment for Type 1 diabetes would be a major drug but Novo isn’t limiting its focus to that opportunity. Rather, Novo wants to apply its growing stem cell know-how to other areas, thereby advancing its broader effort to diversify beyond diabetes.
Novo has teamed up with Sweden’s BioLamina and related groups for the stem cell therapy expansion. The agreements give Novo a chance to license the fruits of BioLamina’s cell culture matrices, which researchers at Lund University and Duke-NUS in Singapore have used to develop therapies aimed at Parkinson’s, chronic heart failure and age-related macular degeneration.
The agreements give Novo the makings of a multiasset, albeit early-stage, stem cell therapy pipeline. Novo wants to enter into more collaborations to expand into other chronic diseases.
Audentes has positive results in early rare disease study
Audentes Therapeutics, Inc. (Nasdaq: BOLD), a biotechnology company focused on developing and commercializing gene therapy products for patients living with serious, life-threatening rare diseases, today announced continuing positive data from the first dose cohort of ASPIRO, a Phase 1/2 clinical trial of AT132 in patients with X-Linked Myotubular Myopathy (XLMTM). ASPIRO is a multicenter, multinational, open-label, ascending dose study to evaluate the safety and preliminary efficacy of AT132 in approximately 12 XLMTM patients less than five years of age. The data were presented during an oral presentation at the 21st annual meeting of the American Society of Gene and Cell Therapies in Chicago, IL.
“We continue to be highly encouraged by the profile of AT132 observed to date in the ASPIRO study,” stated Dr. Suyash Prasad, Senior Vice President and Chief Medical Officer of Audentes. “Patients treated in the initial cohort continue to make advancements in neuromuscular and respiratory function, highlighted by the fact that our earliest treated patient has now been ventilator independent for over eight weeks.”
Dr. Prasad continued, “We are pleased to see the encouraging trends in safety and efficacy continue in the recently enrolled Cohort 1 expansion patients, with early gains in CHOP-INTEND and MIP observed by the four-week timepoint and no significant treatment-related adverse events reported to date. We remain inspired by our patients and their families, and we look forward to continuing our work with the XLMTM community to advance this important work as rapidly as possible.”
WuXi and Sinobioway add capacity to nab expected wave of Chinese biologics
China’s new Marketing Authorization Holder (MAH) program, which allows drugmakers to contract production instead of building their own plants, appears to have set off a biologics production race of sorts, leading CMOs in China to invest hundreds of millions in new plant projects.
China’s WuXi Biologics said on Wednesday that it would build an R&D and clinical and commercial production center in Shijiazhuang that will eventually employ 1,000 workers.
The company will invest $240 million in the new facility, which will have 48,000 liter bioreactor capacity. Work is to begin next year and the first phase completed in 2020.
“We are very pleased to establish the largest biologics center in northern China, which will enable local companies to more effectively develop and manufacture biologics and in the meantime provide a robust supply chain network for our global clients,” said WuXi CEO Chris Chen in a statement. “This expansion will allow us great access to local talents, markets and government support.”
WuXi already has seven manufacturing facilities in the country, including one that it boasts is the largest single-use bioreactor manufacturing facility in the country. The plant in Wuxi City has about a 30,000 liter bioreactor capacity.
Its latest announcement comes just days after China’s Shandong Sinobioway Biomedicine Co. said it will invest $471.6 million by 2023 on a biologics manufacturing facility that eventually will have 500,000 liters of capacity. The Sinobioway facility, which is slated to be built on a 15,404-square-meter site at the Sinobioway biomedical industry park in Anhui, will include labs, storage and quality control areas, as well as bioreactor capacity.
While some in the industry wonder how the companies can generate enough business to fill all of that planned capacity, both companies cited China’s new Marketing Authorization Holder program. The test program allows drugmakers to contract out manufacturing. In the past, approval required that manufacturing be handled by the drugmaker.
Most Big Pharma players have already built their own biologics plants to produce drugs in the country but the new regs removed a huge financial burden from smaller players. When the pilot program was announced in 2016, the Ropes & Gray law firm advised drugmakers and contractors to take advantage.
“The MAH system demonstrates China’s strong momentum to unleash innovation in the pharmaceutical sector,” the law firm said. “Both local and foreign players should consider leveraging the regulatory flexibility of the pilot program to acquire or spin off assets and to utilize GMP-certified contract manufacturing arrangements. Contract manufacturers are also advised to revisit potential opportunities in the Chinese market.”
The regulatory shift has drawn players from outside as well as inside China. Germany’s Boehringer Ingelheim is among those. Last year it opened a biologics plant with one single-use bioreactor, but the plant was designed to install additional 2000-L single-use bioreactors and fill/finish capabilities if demand calls for that.
WuXi’s has found demand robust for its facilities. CEO Chen pointed out the company already is working on dozens of biologic drugs for clients.
“With this investment and current 161 biologics programs that WuXi Biologics will manufacture, we will quickly and cost-effectively expand our manufacturing capacity to meet our partners’ needs and become one of the global CMO leaders.”
In March it won FDA approval to produce a novel HIV med for Taiwan-based TaiMed Biologics at its original plant for cell-based drugs near Shanghai. While WuXi figures many of its clients will be domestic drugmakers, it also is looking to draw in global players.
It is so confident of its capabilities that it is now building a facility in Europe to address the European market directly. The €325 million ($392 million) biologics facility in Dundalk, Ireland, its first outside of China, is slated to be complete in 2021 and to employ 400 workers.
FDA chief: 1st-ever withdrawal drug could get more into addiction therapy
Patients who go off opioid painkillers face excruciating withdrawal symptoms such as anxiety, nausea, vomiting, insomnia, muscle aches and more. Now, thanks to an FDA approval for US WorldMeds’ Lucemyra, they’ll have the first drug designed to fight those symptoms.
Lucemyra won its FDA nod on Wednesday based on two trials showing that the drug reduced severe withdrawal symptoms better than placebo. Plus, more patients in the Lucemyra arm completed a seven-day opioid discontinuation treatment.
Used for more than two decades in the U.K., the oral drug isn’t meant to treat opioid addiction or curb drug cravings. But it can be used as part of a long-term plan for quitting the powerful painkillers and staying opioid-free long-term, the FDA said.
For instance, Lucemyra could be a springboard into a long-term medication-assisted addiction therapy such as Vivitrol (naltrexone), an Alkermes drug that blocks the effects of opioids on the brain—meaning one can’t feel the intoxication. Lucemyra works by reducing the release of norepinephrine, a chemical in the body believed to play a part in withdrawal symptoms.
“We know that the physical symptoms of opioid withdrawal can be one of the biggest barriers for patients seeking help and ultimately overcoming addiction,” said FDA Commissioner Scott Gottlieb, M.D., in a statement. “The fear of experiencing withdrawal symptoms often prevents those suffering from opioid addiction from seeking help. And those who seek assistance may relapse due to continued withdrawal symptoms.”
For patients using opioids appropriately, withdrawal is usually managed by slow reduction in doses. Patients abusing the drugs can suffer more severe withdrawal symptoms, and those who intend to take Vivitrol or another addiction drug need to withdraw from opioids first.
Because Lucemyra can make withdrawal process easier for patients, National Institute on Drug Abuse Director Nora Volkow, M.D., argues it could boost wider use of Vivitrol, which differentiates itself from methadone and buprenorphine, two other addiction treatments that belong to the opioid family.
“Lofexidine could benefit the thousands of Americans seeking medical help for their opioid addiction, by helping them stick to their detoxification or treatment regimens,” Volkow said in her blog.
The FDA granted Lucemyra the go-ahead after previous priority review and fast track designations, and it comes after an independent scientific panel voted 11-1 in favor of its approval.
The agency is now requiring 15 postmarketing studies. These include animal and in-human studies to examine long-term use of Lucemyra, potentially during a gradual opioid dose-reduction process rather than sudden removal. Lucemyra is currently only approved for no more than 14 days of treatment. Studies will also take place in pediatric patients, including on newborns with neonatal opioid withdrawal and on different age groups of children.
Kentucky-based US WorldMeds expects to launch Lucemyra in the U.S. in August.
Eiger expands licensing pact with Merck on Progeria med
Eiger BioPharmaceuticals, Inc. (EIGR), focused on the development and commercialization of targeted therapies for rare diseases, announced today that it has expanded its licensing agreement with Merck, known as MSD outside the United States and Canada, to include rights to develop the investigational farnesyltransferase inhibitor lonafarnib for the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria), a rare and fatal genetic condition characterized by accelerated aging in children. The expanded agreement provides Eiger with commercial and distribution rights to lonafarnib across the licensed and approved indications in the future. Concurrently, Eiger announced that it has completed a collaboration agreement with The Progeria Research Foundation (PRF). Eiger, at its sole cost and expense, will provide lonafarnib for ongoing clinical trials and expanded access in Progeria and be responsible for any potential filing of an NDA for the Progeria indication based on PRF data. Eiger plans to seek FDA guidance regarding a potential regulatory approval for lonafarnib in Progeria.
Merck previously provided lonafarnib free of charge for clinical studies supported by PRF in Progeria. Following the transfer of manufacturing technology for lonafarnib from Merck to Eiger in 2015, Eiger continued to provide lonafarnib for investigational use, and a collaboration with PRF emerged. Eiger plans to seek guidance from the FDA regarding data already generated in multiple clinical studies conducted and completed by PRF evaluating lonafarnib in Progeria. Under the agreement with Merck, Eiger will be responsible for regulatory execution, commercialization and distribution activities of lonafarnib for Progeria. Eiger is also preparing to evaluate lonafarnib in a Phase 3 clinical trial for the treatment of hepatitis delta virus (HDV) infection.
“Continued patient access to lonafarnib was the fundamental motivation for these agreements,” said David Cory, President and CEO of Eiger. “Eiger will provide lonafarnib for ongoing clinical trials and expanded access in Progeria and work together with PRF to seek regulatory guidance on a pathway toward regulatory approval of lonafarnib for use in children with Progeria.”
“Our mission at PRF is to discover treatments and the cure for Progeria, and its aging-related disorders, including heart disease,” said Leslie Gordon, MD, PhD, Medical Director and Co-Founder of The Progeria Research Foundation. “In a relatively short time, we have achieved extraordinary progress towards our mission including the Progeria gene discovery in 2003, the first clinical trial in Progeria initiated in 2007, and clinical evidence of a survival benefit for children administered lonafarnib. We are indebted to Merck for supplying lonafarnib free of charge to PRF-supported clinical trials, and for facilitating our new partnership with Eiger. We look forward to collaborating with Eiger as we pursue pathways for regulatory approval of lonafarnib in Progeria.”
Syndax claims biomarker predicts larger benefit of combo lung cancer med
Syndax Pharmaceuticals’ combination of its HDAC inhibitor entinostat with Merck’s anti-PD-1 therapy Keytruda may have posted small gains in an ongoing phase 1b/2 study in non-small cell lung cancer, but the company believes it has identified an enrichment biomarker that could predict increased clinical benefit overall.
In 57 patients that had progressed after chemotherapy and PD-1 treatments, six showed partial responses to the entinostat-Keytruda combination, for an 11% objective response rate. The median duration of response was 4.6 months, according to Syndax.
Blood samples identified a subset of patients with higher baseline levels of classical blood monocytes that appeared to fare better with the combination regimen: with an ORR of 29% and a progression-free survival of 5.4 months, the subset nearly doubled the 2.8-month benefit seen in historical NSCLC patients treated with third-line chemotherapy.
By comparison, patients with lower monocyte levels had an ORR of 5% and a PFS of 2.5 months, below the overall patient population’s 2.7.
“Monocyte levels may reflect the ability of the immune system to respond after elimination of immune suppression,” said Dmitry Gabrilovich, Christopher M. Davis Professor and leader of the immunology, microenvironment and metastasis program at The Wistar Institute. The company plans to present the study’s results at the annual meeting of the American Society of Clinical Oncology this June.
On a conference call with investors, Syndax estimated about 30,000 patients would qualify annually under this biomarker, after progressing through first-, second- or third-line treatments including PD-1 and PD-L1 inhibitors.
The company plans to launch a registration trial by the end of this year, gathering data for possible submissions in both the biomarker-enriched and the wider, “all-comers” populations in NSCLC. Syndax will meet with FDA and European officials for guidance in protocol design, with results expected in 2020.
The phase 1b/2 study also enrolled cohorts in melanoma and microsatellite stable colorectal cancer—and while objective responses were observed across all cohorts, the company’s future development plans in these areas remain uncertain.
In melanoma, an ORR of 18% has led Syndax to not consider a registration trial at this time, and instead continue biomarker analysis. The company said it would feel more comfortable with correlative data like it found in NSCLC.
In MSS-CRC, following discussions with Merck, Syndax plans to expand enrollment from 16 to 37 patients into the first stage of a two-stage study by the end of the second quarter. Three responses will be required to advance to the second stage, where an additional 47 patients would be enrolled, with that decision scheduled for the first half of next year.
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