BioXcel Therapeutics announced proof-of-concept data from its Phase 1b study of intravenously-administered dexmedetomidine in patients suffering from opioid withdrawal symptoms. The positive data from this Phase 1b trial provides evidence to expand the potential market for BXCL501, a proprietary sublingual film of Dex, beyond its current focus for acute treatment of agitation in neuropsychiatric indications. The study further confirms that BXCL501’s selective alpha-2a adrenergic receptor mechanism has potential application in opioid withdrawal symptoms, in addition to the acute treatment of agitation in schizophrenia, bipolar disorder and dementia. Opioid addiction is difficult to overcome largely because of the severe symptoms associated with withdrawal, an area in need of more effective non-opioid treatment options. BTI conducted the clinical study in a total of 15 patients with opioid dependence. Ten subjects were enrolled in the treatment arm while five subjects were enrolled in the placebo arm. Symptoms of opioid withdrawal were evaluated using the Clinical Opioid Withdrawal Scale, or COWS, an 11-item scale that measures a constellation of withdrawal symptoms experienced after abstaining from opioid use. All ten subjects receiving IV Dex responded to treatment, while there were no responders in the placebo arm. Results from this study demonstrated that IV Dex effectively mitigated the physiological symptoms of opioid withdrawal. These encouraging results support further expansion of BXCL501 for the treatment of withdrawal symptoms associated with opioid abuse. Additionally, previously published studies support the potential of Dex as an adjunctive treatment for symptoms of alcohol withdrawal.
https://thefly.com/landingPageNews.php?id=2858319
Monday, February 4, 2019
Neurotrope in R&D pact with National Cancer Institute on leukemia med
Neurotrope Inc. NTRP, +1.65% a clinical-stage biopharmaceutical company developing novel therapies for neurodegenerative diseases, including Alzheimer’s disease (AD), today announced that it has entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) for the research and clinical development of Bryostatin-1. Under the CRADA, Neurotrope will collaborate with the NCI’s Center for Cancer Research, Pediatric Oncology Branch (POB) to develop a Phase I clinical trial testing the safety and toxicity of Bryostatin-1 in children and young adults with CD22 + leukemia and B-cell lymphoma. In the growing era of highly effective immunotherapies targeting cell-surface antigens (e.g., CAR-T cell therapy), and the recognition that antigen modulation plays a critical role in evasion of response to immunotherapy, the ability for Bryostatin-1 to upregulate CD22 may serve a synergistic role in enhancing the response to a host of CD22 targeted therapies.
Nirali N. Shah, M.D. of the NCI’s POB will be Principal Investigator for the study, and Daniel Alkon, M.D., President and Chief Scientific Officer of Neurotrope, will serve as Co- Principal Investigator.
“We believe that this collaboration with the NCI’s Center for Cancer Research provides further validation of the potential for Bryostatin-1 to affect disease pathways across a broad spectrum of indications,” said Dr. Alkon. “In oncology, Bryostatin’s potential capability to increase CD22 expression may enhance the development of newer and more effective therapies for children and young adults suffering with CD22-positive leukemia and B-cell lymphoma. The enthusiasm for this collaboration stems from the POB’s long vested interest and experience targeting CD22, and we look forward to leveraging the expertise of Dr. Shah and her team to enhance our ongoing efforts to identify the most promising potential applications for Bryostatin-1.”
Bryostatin-1 is a macrocytic lactone shown to increase CD22 expression in chronic lymphocytic leukemia. Under the CRADA, Bryostatin-1 is expected to be tested in the clinic to evaluate its ability to modulate CD22 in patients with relapsed/refractory CD22+ disease, while evaluating safety, toxicity and overall response.
“The initiation of our oncology collaboration with the NCI, coupled with the recent positive safety evaluation of our confirmatory Phase 2 AD trial, both demonstrate Bryostatin’s broad potential,” stated Dr. Charles Ryan, Chief Executive Officer of Neurotrope. “We enter 2019 with strong momentum clinically as well as operationally, with the successful completion of a financing in December 2018. We expect that 2019 will be a transformational year for Neurotrope as we move toward data in our AD program in the second half of the year, and seek out additional collaborations to fully explore the platform potential of Bryostatin-1.”
Neurotrope also announced today the completion of the first safety evaluation of the Company’s ongoing, placebo-controlled confirmatory Phase 2 trial evaluating Bryostatin-1 (20 µg) in 100 moderate to severe Alzheimer’s disease patients not on memantine. The study’s data safety and monitoring board found no safety concerns and recommended continuation of the trial as designed. Enrollment in the study, which was initiated in July 2018, is proceeding as planned, with data expected during the second half of 2019.
Raymond James says to ‘back up the truck’ on Intercept pre-Regenerate data
Raymond James analyst Steven Seedhouse upgraded Intercept to Strong Buy from Outperform and raised his price target to $184 from $125. The analyst cites his “unusually high amount of conviction in REGENERATE” trial data, noting that all the attempts to test his confidence in the investment story have only made him more bullish. Seedhouse states the Street has not fully accepted his expectation that the data will not be a headwind to the program’s success, adding that his key questions heading into the release will be around the efficacy on both primary endpoints and the safety profile of the trial.
https://thefly.com/landingPageNews.php?id=2858357
https://thefly.com/landingPageNews.php?id=2858357
Brexit: Care home and hospital caterers stockpiling food
Major suppliers to care homes and hospitals are stockpiling food to offset the potential disruption of a no-deal Brexit.
Apetito and Bidfood, who between them supply thousands of care providers, said they were holding extra inventory in case of supply chain problems.
Both said they were prepared but Apetito said it feared others were not.
“We are in a strong position,” said Apetito UK boss Paul Freeston.
“But some firms would not be able to build up big stocks,” like his firm, he said. “Or if they are doing fresh produce they would have to stop. A Hard Brexit could cause them significant economic difficulties.”
Apetito provides pre-made meals to more than 400 hospitals and 450 care homes, as well as 100,000 vulnerable people in their homes.
Mr Freeston said it was spending £5m in building its inventory ahead of Brexit – doubling the raw materials it holds from four to eight weeks’ of stock and pre-made meals from five to six weeks’.
But if the disruption lasted much longer than 12 to 16 weeks, the firm would have “very real difficulties”, because it supplies specialist food for elderly people and those with critical conditions.
But if there are backlogs at UK ports in the event of a no-deal, “the quality of food could suffer and our product range would really narrow”, Mr Freeston said.
The other worry is that if the UK suddenly started trading on World Trade Organisation terms with the EU, the cost of raw materials could jump – and Britain imports about a third of its food from the bloc.
The concerns are shared by Bidfood, which supplies the kitchens of 4,000 care homes and 950 hospitals across the UK, as well as supermarkets, schools and prisons.
Jim Gouldie, its supply chain and technical services director, said the firm had “looked carefully” at products needed by sectors with a “duty of care” and invested in additional warehousing.
Meanwhile Anglia Crown, which manufactures meals for 100 hospital sites, told the BBC it was worried about prices rising after Brexit. A spokeswoman said the company was agreeing prices for “as many commodities as possible, especially any bought in from Europe”.
Are providers secure?
Despite the warnings, the National Care Association said most of the care homes it represents are prepared for any no-deal disruption and have enough food stocks in place – even if that means relying on dried or canned food to carry them through.
But boss Nadra Ahmed is worried that any price shocks to suppliers could end up being passed on to providers.
“Care providers are struggling with funding and recruitment issues already so any increases will increase the challenges they face.”
The Hospital Caterers Association (HCA), which represents hospital catering companies, says most of his members have been preparing for Brexit for some time. And while he is not overly worried about a no deal, he does expect some short term volatility after Brexit.
“A number are making arrangements to increase their stock holding – either on site or by securing commitments from their long-established suppliers,” he says.
“But this clearly is not possible for perishable goods. It is imperative that we ensure continuity of supply to minimise any potential disruption to patients’ menus.”
A government spokesperson said: “Our priority is to make sure that patients continue to receive the same high standard of care.
“We are working closely with the NHS, Defra and healthcare providers to ensure the uninterrupted supply of food and specialised nutritional products to patients, as part of our preparations for a no-deal EU Exit.”
Long-Term Prescription Opioid Use in Severe Osteoarthritis Varies by Region
Target Audience and Goal Statement: Rheumatologists, pain specialists, geriatricians, orthopedists, and primary care physicians
The goal was to examine prescription opioid use among Medicare enrollees with severe osteoarthritis who underwent total joint replacements (TJRs).
Questions Addressed:
- What was the level of opioid use in the year preceding a TJR and overall among Medicare beneficiaries with advanced osteoarthritis and an indication for pain control?
- Were there any geographical variations in rates of treatment with long-term opioid therapy in osteoarthritis, which was not fully explained by differences in access to healthcare providers, varying case-mix, or state-level policies?
Synopsis and Perspective:
Based on a recent U.S. News & World Report analysis, the opioid crisis is here to stay for years. This epidemic, which is affecting both children and adults, started 40 years ago and grew exponentially in the ensuing decades. The Department of Health and Human Services statedthat “increased prescription of opioid medications led to widespread misuse of both prescription and non-prescription opioids before it became clear that these medications could indeed be highly addictive.”
Many opioid prescriptions in the U.S. are written for osteoarthritis of the hip or knee — a common reason for chronic pain that today affects nearly 30 million U.S. adults. In the earlier stages of the disease, treatment usually involves non-steroidal anti-inflammatory drugs, steroids, and opioid analgesics. Patients with severe pain that is inadequately controlled by medications are usually candidates for TJRs.
Very little was known about real-world long-term use of opioids in older patients with osteoarthritis. Therefore, Rishi J. Desai, PhD, of Harvard Medical School in Boston, and colleagues, set out to conduct “an observational cohort study in a nationwide sample of Medicare enrollees with severe osteoarthritis to describe long-term opioid use and to evaluate the role of geography and healthcare access in d
Medicare beneficiaries (n=358,121; mean age 74) who underwent TJRs for the treatment of osteoarthritis at 4,080 primary care service areas from 2010 to 2014, where opioid use was reported, were included in this study. The main outcome of interest was the percentage of patients on long-term opioid therapy within each area. Desai’s group also evaluated opioid use in the year preceding each TJR procedure. Another variable of interest was opioid use by geographic region. New York was used as the reference state because of a large sample size and consistently low opioid use reported in previous investigations, the authors noted.
Average daily dose was calculated in morphine milligram equivalents (MME). According to a 2016 CDC guideline, caution should be exercised when prescribing opioids at any dosage, but special attention needs to be paid to the benefit-risk profile when the dose is increased to ≥50 MME per day. A decision to titrate dosage up to ≥90 MME should be carefully justified or avoided if possible.
Most of the patients included were women (67.8%) and white (91.9%). Back and neuropathic pain were highly prevalent among all patients. Of these study subjects, 42.3% were short-term opioid users (<90 days), 16.5% were long-term users (≥90 days), and 40.9% were non-users. Opioid consumption among long-term users was relatively stable over a 3-year period (16.8% in 2011 and 2012, 16.6% in 2013, and 16.3% in 2014).
The median length of use in the long-term group was 7 months, compared with 15 days in the short-term group. About 19% of the long-term users and 15.9% of the short-term users consumed more than 50 MME per day. Use of several opioids were higher in long-term compared with short-term users: tramadol (45.8% vs 36.8%, respectively), oxycodone (32.2% vs 21.7%), and fentanyl (6.2% vs 0.5%).
Opioid prescription rates varied across the U.S., with generally higher rates noted in the South compared with the Northeastern and Midwestern regions. The unadjusted mean percentage of long-term opioid users varied widely across states, ranging from 8.9% in Minnesota to 26.4% in Alabama.
Access to rheumatologists was not associated with long-term opioid use. When comparing areas with the highest concentration of primary care services (>8.6 per 1,000 beneficiaries) versus lowest (<3.6 per 1,000), only a modest association was seen between access to primary care physicians and rates of long-term opioid use (adjusted mean difference 1.4%, 95% CI 0.8%-2.0%).
Study limitations included not having data on pain severity or pain-related functioning for patients in this cohort, limited generalizability (TJR use among blacks was 40% lower than among whites), historical data that may not have captured post-2014 shifts in prescription opioid use patterns in this population (in response to the growing awareness about the opioid epidemic), and the fact that no evaluations were performed to see whether TJR changed opioid use in these patients.
Source Reference: Arthritis & Rheumatology, Jan. 28 2019, DOI: 10.1002/art.40834
Study Highlights: Explanation of Findings
Osteoarthritis is one of the most common reasons for chronic pain in the U.S. The current study had several strengths, e.g., comprehensive risk-adjustment based on patient demographics, comorbid conditions, as well as variation in state-level policies. One in six Medicare enrollees with osteoarthritis used long-term prescription opioids (≥90 days) for pain management in the year leading up to a TJR procedure (average duration ~7 months). Some of the long-term users (~20%) fell into the CDC-defined category of high-risk for opioid-related harms because they consumed an average daily dose of ≥50 MME.
Long-term opioid use observed in this study was more than twofold higher than previously reported estimates, according to the authors. Patients with severe osteoarthritis represent a particularly high-risk group, as they have substantially higher rates of long-term prescription opioid use compared to an average Medicare enrollee.
Results from a separate randomized trial did not support the initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain. A Cochrane review of opioids for osteoarthritis stated that “for the pain outcome in particular, observed effects were of questionable clinical relevance.” Taken together with current findings, the need for caution in prescribing opioids for patients with severe osteoarthritis is vital and the authors urged that “special emphasis on periodically monitoring prescription opioid use is required to ensure benefits outweigh risks at prescribed doses.”
Geographic variations in opioid prescription practices noted in this study have also been observed by other researchers who were examining separate outcomes. Regional variations could not fully be explained by differences in access to primary care physicians or rheumatologists, variations in patient characteristics, or state-level policies, including medical marijuana and prescription drug monitoring programs. Overall, the results underscored the need for geographically targeted interventions to ensure widespread dissemination and implementation of safe opioid prescribing guidelines to make a meaningful impact on prescribing practices.
The CDC’s guidelines for the responsible prescription of opioids for chronic pain involves key criteria:
- Use non-opioid therapies, either alone or in combination with opioid therapy, for treatment of chronic pain; and only consider opioid therapy if the benefits for pain are expected to outweigh the risks
- Start with the lowest effective dosage and short-acting opioids instead of extended-release/long-acting opioids, when using opioids
- Follow-up visits should include assessments of whether opioids are improving pain and function without causing harm
Primary Source
Arthritis & Rheumatology
Secondary Source
MedPage Today
Source Reference: Walsh N “Opioids in OA: A Matter of Geography” 2019.
What’s New in Biodefense
In 2001, only a week after the 9/11 attacks, members of the media and certain politicians received letters containing anthrax spores. The overall bioterror attacks killed five people and infected 17 more. Eventually, Bruce Ivins, a researcher at the federal government’s biodefense laboratories at Fort Detrick in Frederick, Maryland, was identified as the suspect. Ivins committed suicide with an overdose of acetaminophen on July 29, 2008.
There have been no major bioterror attacks in the U.S. since, although there have been a number of ricin threats—a poison sourced from castor beans—including a letter sent to the U.S. Pentagon containing ricin particles on October 2, 2018. They turned out to be castor seeds, from which ricin is created. Utah resident William Clyde Allen III was arrested and confessed.
Even more notoriously, several people were attacked in the UK by a nerve agent, Novichok, developed by the Soviet Union in the 1970s and 1980s. In March 2018, former Russian military officer and double agent for the UK’s intelligence services, Sergei Skripal, and his daughter Yulia Skripal, were poisoned by Novichok, allegedly by Russian agents, GRU Colonel Anatoliy Chepiga and Dr. Alexander Mishkin, also of the GRU.
Although bioterrorism doesn’t get the kind of attention more traditional bombings and shootings receive, the biotech industry and the federal government are paying attention and actively funding and developing countermeasures to potential bioterror, military and public health emergencies. In fact, in 2015, the global biodefense market was about $9.5 billion. Grand View Research projects that same market to grow to about $18 billion by 2025.
Here’s a look at just some of what’s going on in the biodefense arena.
BARDA
The Biomedical Advanced Research and Development Authority (BARDA) is part of the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response. It was established in 2006 to help keep the country safe from chemical, biological, radiological, and nuclear (CBRN) threats, in addition to a focus on pandemic influenza (PI) and emerging infectious diseases (EID).
As such, BARDA provides funding and technical assistance to a number of companies and institutions working in these areas.
One of BARDA’s initiatives is dubbed DRIVe (Division of Research, Innovation, and Ventures). DRIVe’s approach is to act more like a strategic investor in private and public companies as well as fund grants. A June 2018 Forbes article noted, “This means that the new division may be able to make direct investments into companies BARDA would like to partner with and derive value by holding equity or equity-like instruments in the venture. Investing in opportunities in this manner offers a pathway to renew funds to reinvest into other ventures deemed essential to the national interest.”
DRIVe’s portfolio includes Emory University’s DeepAISE algorithm for sepsis, Cytovale’s SeptiScan System, Biobeat’s Wrist Watch, Prenosis’ Predictive Analytic Assay and others.
A Ricin Treatment
Recently, researchers at Tulane National Primate Research Center described an experimental drug that appears to counteract the effects of ricin. The research was published in the journal JCI Insight.
The drug, developed by researchers at Tulane, Mapp Biopharmaceutical, University of Texas Southwestern Medical Center, and the New York State Department of Health is a humanized monoclonal antibody against the ricin toxin. There appears, at least in primates, to be a relatively short exposure window of about four hours, when the drug was most successful. The researchers expect to work on a stronger version that could be useful further out from initial ricin exposure.
“Clinically, there is no treatment that can be administered currently to save someone in the event of an exposure to this toxin,” stated study first author Chad Roy, director of biodefense research programs at Tulane. “Our study shows proof of concept in a near-clinical animal model, the nonhuman primate, that we finally have a life-saving treatment against one of the world’s most notorious toxin agents.”
Princeton, NJ-based Soligenix also has a ricin toxin vaccine candidate, RiVax, as part of its Vaccines/BioDefense business segment. The company presented data on the vaccine in November 2018 at the Fourth International Conference on Vaccines Research & Development.
Anthrax Vaccine
On December 31, 2018, Emergent BioSolutions submitted an application to the U.S. Food and Drug Administration (FDA) for emergency use authorization (EUA) of its anthrax vaccine candidate, NuThrax. The FDA is expected to make a decision in the first half of this year.
NuThrax is the company’s next-generation anthrax vaccine candidate for post-exposure prophylaxis. It is a two-dose regimen. The company is hoping it can receive EUA, which would allow it to be included in the Strategic National Stockpile (SNS) this year.
In September 2016, the company received a $1.6 billion contract with BARDA to develop and deliver NuThrax. The company also markets a smallpox vaccine, ACAM2000, and an anthrax monoclonal antibody, Raxibacumab. In the fourth quarter of 2017, Sanofi acquired ACAM2000 and GlaxoSmithKline acquired Raxibacumab.
Regeneron: Euro Panel Recommends OK of Praluent for Cardiovascular Disease
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Praluent® (alirocumab) Injection, recommending a new indication to reduce cardiovascular risk by lowering low-density lipoprotein cholesterol (LDL-C) levels as an adjunct to correction of other risk factors in adults with established atherosclerotic cardiovascular disease (ASCVD). Praluent should be used in addition to maximally-tolerated statins or can be used alone in patients intolerant to or inappropriate for statin therapy.
ASCVD is an umbrella term, defined as a build-up of plaque in the arteries that can lead to reduced blood flow and a number of serious conditions such as stroke, peripheral artery disease and acute coronary syndrome (ACS), which includes heart attack and unstable angina.
The CHMP opinion is based on data from ODYSSEY OUTCOMES, a Phase 3 cardiovascular outcomes trial that assessed the effect of Praluent in 18,924 patients who had an ACS between 1-12 months (median 2.6 months) before enrolling in the trial. Results from the ODYSSEY OUTCOMES trial were published in The New England Journal of Medicine in 2018.
The European Commission is expected to make a final decision in the coming months. Data from ODYSSEY OUTCOMES have also been submitted to the U.S. Food and Drug Administration (FDA), with a target action date of April 28, 2019.
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