Search This Blog

Tuesday, June 11, 2019

Genfit defends elafibranor after CymaBay-linked selloff

In the wake of a selloff stoked by disappointing results for CymaBay’s (CBAY-45.4%) NASH candidate seladelpar, Genfit SA (GNFT -14.2%) has released a letter to investors aimed at clearing up any “confusion” with elafibranor. To wit:
FDA approval will be based on NASH resolution without worsening of fibrosis via histological examination (evaluating tissue samples with a microscope). By this definition, elafibranor was successful in a Phase 2b study. An ongoing Phase 3, RESOLVE-IT, has the same endpoint. Preliminary data should be available by year-end.
The reduction in liver fat content, the endpoint in CymaBay’s Phase 2b studythat caused the selloff, is not considered a relevant efficacy endpoint by regulators.
It has also shown beneficial effects on HbA1C, insulin sensitivity and “bad cholesterol.”

Dassault called near Medidata purchase

Dassault Systemes (OTCPK:DASTF,OTCPK:DASTY) is nearing a deal to acquire Medidata Solutions (NASDAQ:MDSO), according to Bloomberg sources.
MDSO shares are up 4.4% after hours to $98.90.

Alzheimer’s Drug May Help Treat Opioid Addiction

The cholinesterase inhibitor galantamine (Razadyne, Janssen) has shown promise as a treatment for opioid addiction, preliminary research suggests.
A secondary analysis of a randomized controlled trial showed reduced opioid use with the cognitive enhancer. Galantamine is thought to have a dual mechanism of action, increasing levels of acetylcholine in the brain and binding to nicotinic receptors, which play a role in addiction to nicotine and other substances.
“My colleagues and I are excited about these preliminary findings, as they could point to new strategies for helping those with opioid use disorder. We hope to pursue this in future research,” principal investigator Kathleen Carroll, PhD, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, said in a news release.
The results were published online June 4 in The American Journal on Addictions.

Anti-Addictive Effect?

Previous clinical research showed galantamine-associated reductions in heavy alcohol and cigarette use. In addition, in preclinical studies, cholinesterase inhibitors reduced self-administration of cocaine, opioids, and nicotine.
This led the investigators to hypothesize that galantamine, or more generally cholinesterase inhibitors, have an ‘anti-addictive’ effect through a common mechanism shared by different drugs of abuse.
To investigate, the researchers conducted a secondary analysis of a randomized, placebo-controlled trial testing the efficacy of galantamine (8 mg daily extended-release) and computerized cognitive behavioral therapy (CBT) as a treatment for cocaine use disorder in patients stabilized on methadone for co-occurring opioid use disorder (OUD).
A total of 120 patients participated (mean age, 38 years; 67% men; 52% white) in the 12-week trial that also included a 6-month follow-up period.
The main findings of the trial showed a significant reduction in frequency of cocaine use over time for galantamine vs placebo and CBT vs standard methadone treatment alone.
The secondary analysis found a “significant main effect” for galantamine vs placebo in terms of the percentage of urine specimens testing negative for opioids, both during treatment (77% vs. 62%; P = .027) and during the 6-month follow-up period (81% vs. 59%, P = .001).
The benefit of galantamine on reduction in opioid use was seen early in treatment, with patients on placebo submitting the first opioid-positive urine specimen much sooner than patients on galantamine (median day, 15 vs. 53; P = .02).

Novel Treatment for OUD

In an accompanying commentary, Scott Moeller, PhD, and Anissa Abi-Dargham, MD, of the Department of Psychiatry, Renaissance School of Medicine at Stony Brook University in Stony Brook, New York, note the study authors “appear to have uncovered a novel and potentially impactful therapeutic for OUD, a disease that is devastating the United States.”
“While the behavioral mechanism remains elusive,” they note, “this report nonetheless suggests numerous exciting directions for future research. Future investigations have the potential to yield valuable information on galantamine as a medication to push forward clinical practice, as well as yield valuable scientific knowledge on the brain cholinergic system and its involvement in OUD and other addictions.
“If the Carroll et al results are replicated and extended in future trials and clinical laboratory studies, and given that galantamine has shown efficacy in other addictions such as alcohol and cigarette smoking, it is possible that galantamine may emerge as an exciting, next‐generation adjunctive medication for improving clinical outcomes in OUD,” Moeller and Abi-Dargham conclude.
The study was supported by a grant from the National Institute on Drug Abuse. Carroll is a member of CBT4CBT LLC, which makes validated forms of CBT4CBT available to qualified clinical providers. Moeller and Abi-Dargham have disclosed no relevant financial relationships.
Am J Addict. Published online June 4, 2019. AbstractEditorial

PFAS in food, and findings from recent FDA surveys

Statement From:
Acting
Commissioner of Food and Drugs – Food and Drug Administration
Norman E. “Ned” Sharpless MD
Deputy Commissioner for Food Policy and Response – Food and Drug Administration
Frank Yiannas
At the U.S. Food and Drug Administration, increasing our scientific knowledge and capabilities is a cornerstone to ensuring the safety of the foods that Americans consume. We do this by reviewing all available scientific evidence to determine the safety of foods and food packaging and conducting our own research to fill in gaps in the science. As part of these efforts, the FDA has been working to develop new methods to quantify certain per- and polyfluoroalkyl substances (PFAS) in foods. We have employed these new methods to test samples of foods Americans typically consume for certain types of PFAS, and today we are making available recently analyzed data from these initial testing initiatives.
Overall, our findings did not detect PFAS in the vast majority of the foods tested. In addition, based on the best available current science, the FDA does not have any indication that these substances are a human health concern, in other words a food safety risk in human food, at the levels found in this limited sampling. These data give our scientists a benchmark to use as we continue our critical work studying this emerging area of science.
Background on PFAS
PFAS are a family of human-made chemicals that are found in a wide range of products used by consumers and industry. There are nearly 5,000 types of PFAS, some of which have been more widely used and studied than others. Many PFAS are impermeable to grease, water and oil. For this reason, beginning in the 1940s, PFAS have been used for many different applications including in stain- and water-resistant fabrics and carpeting, cleaning products, paints and fire-fighting foams, as well as in limited, authorized uses in cookware and food packaging and processing, referred to as food contact substances.
The widespread use of PFAS and their ability to remain intact in the environment means that over time PFAS levels from past and current uses can result in increasing levels of contamination of groundwater and soil. This same accumulation also can occur in humans and animals, with PFAS found in the blood of humans and animals worldwide. While the science surrounding the potential health effects of PFAS is developing, current evidence suggests that the bioaccumulation of certain PFAS may cause serious health conditions. However, with the decrease in production and use of certain PFAS, levels in humans in the U.S. have been declining.
PFAS can occur in food through environmental contamination, including contaminated water and soil used to grow the food. This type of contamination can occur in a specific geographic area; for example, a water well or farm near an industrial facility where PFAS were produced, or an oil refinery, airfield, or other location at which PFAS were used for firefighting. PFAS can also come into contact with food as a result of the limited authorized uses as food contact substances.
FDA Testing
Addressing potential effects of Americans’ PFAS exposure is a national priority and effort and work is underway in this area by several government agencies. The U.S. Environmental Protection Agency, the U.S. Department of Agriculture, the National Institutes of Health, and the Centers for Disease Control and Prevention are advancing knowledge around environmental exposures and potential health risks from PFAS, and the Agency is working on issues related to PFAS contamination with these and other federal partners, including the Department of Defense. State health partners are also investigating exposure and working to reduce exposure in local communities. The FDA recognizes its important role in generating, applying and evaluating the science that is needed to begin to estimate exposures from food. As we continue this research, we will be better able to detect, evaluate, and respond more quickly to potential contamination issues involving food.
The FDA has tested foods for PFAS coming from specific geographic areas with known environmental contamination. Recent limited surveys were conducted on dairy products from certain farms in New Mexico and produce from North Carolina, both of which were from specific areas with known PFAS contamination. For every sample for which PFAS was detected, a safety assessment was performed by FDA scientists. In the case of one dairy farm in New Mexico, milk samples were determined to be a potential health concern and all milk from the farm was discarded and not distributed into the American food supply, and milk production from those cattle has been suspended. The Agency continues to work closely with our regulatory partners in the New Mexico Department of Agriculture on these issues. In the case of the produce samples from North Carolina, the levels of PFAS detected were low and, based on our safety assessment using the best available science, samples were determined not likely to be a health concern at the levels found through testing.
To conduct these safety assessments, the FDA reviews relevant information, such as the levels of PFAS found in that food, consumption of that food and the most current toxicological information for PFAS, which we use to determine whether the levels of PFAS found in that food may pose a health concern, especially to vulnerable populations.
Over the last year, we have expanded our testing to analyze for PFAS in foods typically eaten by Americans, and not associated with specific contamination areas. The samples analyzed were from foods originally collected as part of the FDA’s Total Diet Study (TDS) in 2017 and analyzed in 2019. This is the first time the FDA has tested for PFAS in such a highly diverse sample of foods. While no PFAS compounds were detected in the majority of the foods sampled, varying levels of PFAS were found in 14 samples out of 91, but our safety assessment determined the products were not likely to be health concern at the levels that were detected. We plan to continue this testing and currently have new TDS samples in the lab for analysis. Combined with our other sampling, the testing will help us calculate the risks of exposure through food.
Next Steps
Our findings on dairy, produce, and the samples from the TDS were recently presented by FDA scientists at this year’s annual meeting of the Society of Environmental Toxicology and Chemistry (SETAC) in Helsinki, Finland. The purpose of this scientific presentation was to share, with the scientific community, the new methodologies being advanced by the FDA for measuring concentrations of these substances across a wide variety of foods, and the early findings generated from the application of these methods. The FDA has published information on PFAS testing in other foods in the past, but FDA scientists also shared information on its recent limited PFAS testing.
Since PFAS contamination is not specific to the U.S., sharing the FDA’s knowledge and analytical advances with scientists from across the world working on this issue is an important part of our work to begin to address this problem globally. Overall, the FDA’s testing to date has shown that very few foods contain detectable levels of PFAS. However, we know that levels may not be uniform and there is more work to be done. To ensure we are taking the best approach to this complex issue, we have established an internal agency PFAS workgroup with representatives from the human and animal foods programs. A key objective of this workgroup is to establish base-line levels for PFAS in foods, which requires data from these initial and future surveys, and will be used to then estimate overall PFAS exposure. The workgroup will use a systematic, risk-based approach to identify and prioritize FDA activities to reduce exposure to PFAS in human and animal food, guided by available data.
Measuring PFAS concentrations in food, estimating dietary exposure and determining the associated health effects is an emerging area of science. Although the FDA’s scientists are at the forefront of developing new and more sensitive testing methods to measure PFAS in foods, this work does not occur in isolation. We’re also working closely with our federal and state partners to advance the science of PFAS detection and better understand the potential health risks associated with PFAS exposure.
As the FDA continues to evaluate the food supply, we are committed to using the advanced analytical capabilities of FDA labs to generate and share new scientific information, such as our testing methodologies. By working closely with our state partners and helping them to develop their own testing capacities, we can work together to increase the baseline knowledge of PFAS occurrence in foods. We will also continue to support response to local requests about known or possible contamination events.
Federal and state partners each have important roles to play to better understand PFAS exposures and potential health effects, and the FDA will continue to work with these partners to help inform appropriate next steps to protect and promote public health. As part of an era of smarter food safety, the FDA is committed to testing more foods, collaborating with other federal agencies, helping states develop their own testing capacities, and continuing to support responses to contamination events. It is critical that we continue to share our knowledge and leverage existing and new resources as local, state and federal agencies work together to study this emerging public health issue.
We remain committed to sharing further updates as our ongoing surveillance work into PFAS exposure in foods continues.

FDA Issues Guidelines for E-Cig Makers Seeking Approval Of Vape Devices

The Food and Drug Administration released new guidelines Tuesday for manufacturers seeking approval to continue selling e-cigarettes, or vaping devices, and the liquids used in the devices to deliver nicotine.

What Happened

Under FDA regulation of e-cigarettes that began in 2016, e-cigarettes, known by the agency as electronic nicotine delivery systems, or ENDS, that were already on the market had to apply for FDA approval to remain available after August 2021.
As part of the process, manufacturers must submit a “Premarket Tobacco Product Application” in which they have to show the product is “appropriate for the protection of public health.”
The guidelines released Tuesday give companies an idea of what they must do to stay on the market. So far, no e-cigarettes have reached the end of the process.

What It Means

“The final guidance issued today provides companies seeking to market e-cigarette and ENDS products with recommendations to consider as they prepare a premarket tobacco product application to help the FDA evaluate the public health benefits and harms of a product,” Acting FDA Commissioner Ned Sharpless said in a statement.
“There are no authorized e-cigarettes currently on the market.”
Federal officials were caught off guard by research showing growing youth use of e-cigarettes last year and have made reducing the figure a major focus.

The E-Cig Market

Juul has about 75 percent of the U.S. e-cigarette market, according to Nielsen data cited by The Financial Times. U.S. cigarette maker Altria Group IncMO 2.03% has a 35-percent stake in Juul.
British American Tobacco PLC BTI 1.32% makes the second-largest e-cigarette brand, Vuse.
Philip Morris International IncPM 1.56% received approval through the premarket application process April 30 to sell an electronic device that heats tobacco without burning it to produce a nicotine-infused aerosol. That device, iQOS, is already sold in several countries.

Merck’s Keytruda, passing Opdivo, bags double head and neck cancer OK

Tuesday was a twofer for Merck & Co., which notched two new FDA approvals for blockbuster Keytruda in previously untreated head and neck cancer patients.
Regulators green-lighted the immuno-oncology star as monotherapy in patients whose tumors bear the biomarker PD-L1 and in combination with a commonly used chemo regimen in patients regardless of PD-L1 status.
The regulatory wins follow a quick review from the agency, which bestowed its priority designation on Keytruda back in February.
FDA staffers based the speed-up on data showing that that, when facing off against a standard-of-care regimen commonly referred to by the name “Extreme,” Keytruda could lower the risk of death by 22% in PD-L1 positive patients. And when paired with chemo, Keytruda slashed the risk of death by 23% regardless of patients’ PD-L1 status.
With the OKs, Keytruda becomes the first in its class of PD-1/PD-L1 drugs into the first-line head and neck cancer market. The go-ahead unlocks potential use in more than 65,000 patients diagnosed each year in the U.S., Merck said.
It also puts Keytruda ahead of archrival Opdivo from Bristol-Myers Squibb, which is cleared only for patients who have already failed on chemo—meaning those who start out on Keytruda instead of chemo won’t be eligible for Opdivo treatment later.

And the last thing Bristol-Myers needs is to trail Keytruda in another therapy area. It’s already ceded the lead in lung cancer, immuno-oncology’s most lucrative market—and Keytruda has run away with it. And in kidney cancer, an area that’s been historically important to Opdivo sales, Merck recently arrived on the scene with a competing combo approval.

$285M counter-marketing cost to correct opioid misinformation: Expert witness

Countless lawsuits have sought to estimate the costs of fixing the U.S. opioid and addiction epidemic. Now, thanks to an expert in Oklahoma’s ongoing trial against Johnson & Johnson, we have one dollar figure.
Oklahoma would have to spend nearly $285 million to mount a counter-marketing campaign that would offset pharma’s influence over pain prescribing, Saxum Strategic Communications chairman and CEO Renzi Stone testified during the state’s trial against Johnson & Johnson on Monday.
And that’s just the cost of a campaign to spread awareness about the harms of opioids, Stone pointed out in testimony reported by the Oklahoman. It doesn’t include the other costs of fixing the state’s opioid crisis.
“Frankly, I am blown away and impressed,” Stone said of J&J’s opioid marketing at the trial, according to testimony posted by the newspaper. “The marketing materials, the depth of research, the significance of stakeholder mapping, the creation of budgets, the size of budgets, the quarterly review is breathtaking.”
Stone said he was “very surprised” about a lack of training on potential abuse in the J&J materials he reviewed for the trial.
On cross-examination by J&J’s attorney Larry Ottaway, Stone admitted his marketing plan wouldn’t require J&J to stop doing anything.
Ottaway also pressed Stone on opioid prescribing decisions. Who should decide how best to treat patients—the state or the physician? Stone responded that it’s “certainly not the sales and marketing team.”
Stone’s testimony came on day 10 of the state’s trial against J&J. Oklahoma sued the company—plus Teva Pharmaceutical and Purdue Pharma—in 2017, but the other drugmakers settled ahead of trial. Purdue and its founding family agreed to fork over $270 million, and Teva settled for $85 million in an agreement that’s still pending court approval.
Oklahoma alleged opioid makers “manipulated” residents into believing their pain drugs were safe to use for long periods of time. Prosecutors aim to recoup “catastrophic” damages the state has suffered as misleading marketing fueled the opioid addiction crisis.
It remains to be seen just how the nationwide opioid litigation will play out, but Oklahoma is certainly an early test for the industry. And it’s a test that pushed two out of three defendants into a settlement as thousands of other lawsuits are pending. J&J has opted not to settle and argues it marketed opioid painkillers responsibly.