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Wednesday, August 3, 2022

FDA Accepts MediWound's Refiling For Severe Thermal Burns Therapy For Review

 The U.S. Food and Drug Administration (FDA) has accepted for review MediWound’s 

 recently re-submitted Biologics License Application (BLA) for its lead asset NexoBrid for eschar removal (debridement) in adults with deep partial-thickness and/or full-thickness thermal burns.

The regulatory agency has assigned a target action date of January 1, 2023.

The re-submission includes data from extensive scrutiny of the pivotal U.S. Phase 3 (DETECT) study of NexoBrid in adult patients with deep partial and/or full-thickness thermal burns up to 30% of total body surface area.

Ofer Gonen, CEO, commented: "We are thrilled to have our application accepted and to be one step closer to commercializing NexoBrid in the U.S. We have seen NexoBrid help burn patients worldwide and knowing that it may be soon available in the United States is very gratifying. We thank both Vericel and BARDA for their leadership and commitment to this important program."

Vericel Corporation 

 holds an exclusive license for North American commercial rights to NexoBrid.

NexoBrid is approved in the European Union and designated as an orphan biologic drug in the United States, European Union and other international markets.

https://www.benzinga.com/general/biotech/22/08/28333311/fda-accepts-mediwounds-refiling-for-severe-thermal-burns-therapy-for-review

Do You Consider Medications to Treat Obesity?

 Do you consider using medications when treating patients for obesity? If you answered no, it's time to make a change in your practice. Our current understanding of obesity as a chronic, progressive, and relapsing disease, just like type 2 diabetes, is useful in making the mindset shift toward a medical treatment model.


Obesity is now considered a disease of energy dysregulation whereby altered biological signals and the environment contribute to weight gain and accumulating excess body fat. As with diabetes, we need to use a variety of approaches to help our patients better manage their obesity. Counseling around choosing a calorie-controlled healthy diet, being more physically activity, and using strategies for behavior change are foundational steps for all patients seeking treatment for obesity.

However, lifestyle management is often not enough for many of our patients, who continue to struggle with their weight and have coexisting medical problems. It is no longer acceptable to simply tell patients to "just try harder" when more effective adjunctive treatments are available. Rather, you should consider whether the patient is a candidate for prescribing a US Food and Drug Administration (FDA)–approved medication for chronic weight management.

How Do Anti-obesity Medications Work?

There are currently five medications approved by the FDA for long-term use — orlistat (Xenical), phentermine/topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), and semaglutide (Wegovy) — and one is approved for short-term use (phentermine). All of these drugs, except orlistat, alter the patient's appetite perception by modifying biological signaling in the brain. Although individual responses vary, patients may feel less hungry, feel fuller after a meal and more content between meals, and have reduced cravings and less thoughts of food. By controlling appetite, the patient is able to adhere to a lower-calorie diet more consistently. For this reason, patients taking medications lose 5%-12% more weight than those following a lifestyle plan alone.

Who Are Candidates for Anti-obesity Medications?

Anti-obesity medications are approved for patients with a body mass index ≥ 30 or a body mass index ≥ 27 with a comorbidity. Additional considerations include patients who are actively engaged in self-care, attentive to their diet but struggling to make dietary changes, are unable to lose or maintain a lower body weight, and have a desire for improved health.

Which medication to choose depends on existing comorbidities, side effects, patient preference, insurance coverage, and cost (if paid out of pocket).

Concomitant treatment of comorbidities is also an important factor. For example, a patient with diabetes would benefit from use of a glucagon like peptide 1 receptor agonist (GLP-1 RA), such as liraglutide or semaglutide, because they are incretin hormone agents used to treat diabetes. Similarly, a patient with a history of migraine headaches may benefit from phentermine-topiramate because topiramate is also approved for migraine prophylaxis. Each medication has its own unique titration schedule, so clinicians need to become familiar with dosing instructions. Regardless of the medication selected, the patient needs to be informed that treatment is intended for long-term use because discontinuation will result in reemergence of increased appetite and weight regain.

How Do Patients Feel About Taking Medications for Chronic Weight Management?

For some patients, there is a stigma around taking weight loss drugs, a concern that they will be perceived as being unable or too weak to manage their weight on their own. This is born of the misbelief that obesity is entirely due to overeating and lack of physical activity. Failure to control body weight is a sign of laziness, lack of personal responsibility, and gluttony. Thus, it follows that taking a medication is the "easy way out."

It is important to convey to the patient that excessive body weight is considered a medical condition, requiring supportive care such as lifestyle counseling, referral to a registered dietitian or health psychologist, prescription of a medication, or consideration of bariatric surgery. Anti-obesity medications assist a patient with appetite control and make dietary adherence more successful.

What Medications Are on the Horizon?

We are entering a new phase of treatment for obesity that is harnessing the appetite-controlling effects of naturally occurring, nutrient-stimulated gastrointestinal and pancreatic hormones that include GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin.

Semaglutide, a second-generation GLP-1 RA, was approved for chronic weight management in 2021 after publication of the STEP randomized controlled trials. In STEP 1, average weight loss at 68 weeks was 15% vs 2.4% with placebo. Semaglutide was also found to be 2.5 times more effective than the first-generation drug liraglutide.

Average body weight reduction with tirzepatide, a new dual GLP-1 and GIP RA, reached 21% after 72 weeks on the 15-mg dose.Additional combination agents and mono-, dual-, and tri-agonists that contain these hormones are currently under investigation.

Putting It All Together

Similar to other chronic medical conditions, we need to use a multi-treatment strategy to help our patients achieve best outcomes. For obesity management, this includes providing lifestyle counseling on choosing a healthy calorie-controlled diet, increasing physical activity, and strategies to implement positive behavioral changes. For many patients, adding an anti-obesity medication to the regimen will enable patients to be more successful in losing weight and for long-term weight maintenance. It is incumbent upon the medical provider to become familiar with the use of available and emerging agents.

Robert F. Kushner, MD

Professor, Department of Medicine and Medical Education, Northwestern University Feinberg School of Medicine; Director, Center for Lifestyle Medicine, Northwestern Medicine, Chicago, Illinois

Disclosure: Robert F. Kushner, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Novo Nordisk; WW; Lilly; Pfizer
Received research grant from: Epitomee

https://www.medscape.com/viewarticle/978136

Top NC Health Official Can Be Sued for COVID Shutdown

 The North Carolina Court of Appeals ruled Tuesday that Gov. Roy Cooper's secretary of health and human services should not be immune from a lawsuit over the administration's restrictions on large gatherings in the early months of the coronavirus pandemic.

The Department of Health and Human Services temporarily shut down Ace Speedway, a small stock car racetrack in Alamance County, in June 2020 after it repeatedly defied Cooper's executive order limiting outdoor crowds to mitigate the spread of COVID-19.

The racetrack filed counterclaims that August, alleging the department unlawfully singled out the business for its acts of protest and violated its employees' constitutional right to earn a living.

The appeals court unanimously upheld a January 2021 trial court ruling denying a DHHS motion to dismiss Ace Speedway's claims that the agency selectively enforced the governor's orders and impeded the racetrack's ability to make money.

"This case makes us consider the use of overwhelming power by the State against the individual liberties of its citizens and how that use of power may be challenged," the judges wrote.

DHHS Secretary Kody Kinsley, whose predecessor filed the 2020 order to close the speedway, argued before the appeals court that executive officials should be immune from civil lawsuits. But the court ruled Ace's claims were "sufficient to survive the secretary's motion to dismiss" the lawsuit.

Three days after Cooper issued an executive order placing a 25-person cap on all outdoor gatherings, Ace Speedway hosted approximately 2,550 spectators for its first race of the season on May 23, 2020.

A sign posted on site at a subsequent race that June labeled the 2,000-person gathering a "peaceful protest of injustice and inequality everywhere," the lawsuit states.

When the speedway continued to draw crowds of 1,000 or more, the governor's office ordered Alamance County Sheriff Terry Johnson to intervene. After Johnson refused to issue a misdemeanor citation, the Cooper administration declared Ace Speedway an "imminent hazard" for the spread of COVID-19 and called for its closure until the emergency order expired.

A court has yet to rule on the merits of Ace Speedway's claims. But the panel of three Republican judges drew attention Tuesday to a clause in the state Constitution guaranteeing North Carolinians a right to the "fruits of their labor." Recent court precedents say the clause is synonymous with the right to earn a living.

The ruling noted that the order to close the racetrack "restricted or otherwise interfered with the lawful operation of a business serving the public."

https://www.medscape.com/viewarticle/978524

Rapid Smell Loss a Biomarker of Alzheimer's Disease Risk?

 Rapid deterioration in sense of smell is a strong predictor of both Alzheimer's-related cognitive impairment and loss of volume in specific brain regions linked to both Alzheimer's disease and smell, according to new research findings.

Olfactory dysfunction is common in late life and well documented among people with Alzheimer's disease. However, it was unknown whether faster olfactory decline predicts either onset of Alzheimer's disease or structural brain changes associated with Alzheimer's disease.

Dr Jayant Pinto

In a study published online in Alzheimer's and Dementia, Jayant M. Pinto, MD, and his colleagues at the University of Chicago Medical Center reported that among older adults with normal cognition at baseline, people who experienced rapid loss of sense of smell were more likely to be subsequently diagnosed with mild cognitive impairment (MCI) or dementia, compared with those who did not.

Participants were recruited from Rush University's Memory and Aging Project, a longitudinal cohort of older adults who undergo yearly cognitive and sensory exams, including a scratch test of 12 common smells to identify. The Rush study "was ahead of the curve in looking at smell," Pinto said in an interview. "It gave us a very valuable resource with which to attack these questions."

Pinto has long investigated links between smell and accelerated aging; in 2014 his group published the finding that olfactory dysfunction could predict death within 5 years in older adults, and in 2018 they reported that olfactory dysfunction could predict dementia.

Smell and Cognition Over Time

For the current study, Pinto said, "we were able to look at the question not just using a single point in time, but a more granular trajectory of smell loss. Measuring change year by year showed that the faster people's sense of smell declined, the more likely they were to be diagnosed with MCI or Alzheimer's disease."

Pinto and his colleagues evaluated results from 515 adults (mean age 76.6, 78% female, 94% White) with no cognitive impairment and at least 3 years of normal results on smell tests at baseline. The subjects were followed for a mean 8 years. One hundred subjects (19%) were diagnosed with MCI or dementia by the end of the study period. A subset of the cohort (n = 121) underwent structural magnetic resonance imaging (MRI) between their final smell tests and the study's end. Of these, most still had normal cognition; 17 individuals had MCI.

Patients' individual trajectories of smell loss were mapped as slopes. After adjusting for expected differences in age and sex, the investigators found steeper decline associated with greater risk of incident MCI or dementia (odds ratio, 1.89; 95% confidence interval, 1.26-2.90; P < .01). The risk was comparable to that of carrying an apo E ε4 allele, the key risk variant for late-onset Alzheimer's disease, but was independent of apo E status. The association was strongest among subjects younger than 76 years.

Olfactory Decline and Brain Volume

Pinto and his colleagues, including lead author Rachel R. Pacyna, a 4th-year medical student at the University of Chicago, also sought to identify brain volume changes corresponding with olfactory decline and Alzheimer's disease. The researchers hypothesized that certain brain regions not seen affected in Alzheimer's disease would remain unchanged regardless of olfactory status, but that regions associated with smell and Alzheimer's disease would see smaller volumes linked with olfactory decline.

Faster olfactory decline did predict lower gray matter volume in olfactory regions, even after controlling for apo E status and other known risk factors. Conversely, cognitively unimpaired patients undergoing MRI saw more gray matter volume in primary olfactory and temporal brain regions, compared with those with cognitive symptoms.

Taken together, the findings suggest that "change in sense of smell is better than looking at sense of smell at one time point," Pinto commented. "There are other reasons people have impaired sense of smell: car accidents, COVID, other viruses and infections. But if you identify on a time course those who are starting to lose it faster, these are the people on whom we need to focus."

Not Yet Diagnostic

More work needs to be done to establish thresholds for smell loss that could be useful in clinical or investigative settings as a marker of dementia risk, Pinto acknowledged. "Everyone gets their hearing tested; everyone gets their vision tested. It's not as easy to get your sense of smell tested. But this study is telling people that if we were to start measuring it routinely, we could actually use it."

Smell testing "could become a component of a diagnostic battery that includes things like genotyping and cerebrospinal fluid markers, but adds a little more information. It could be useful in clinical prevention trials to identify people at the highest risk, as smell loss presents quite a few years before MCI or Alzheimer's disease."

The investigators acknowledged that their findings need to be replicated in more diverse cohorts that better represent the Alzheimer's population in the United States. Another limitation of their study, they said, was that the method used to calculate the rate of olfactory decline "was based on slope of measured time points assuming linearity, which may oversimplify the complexity of olfactory changes in normal aging and during the preclinical Alzheimer's disease period." The study was funded by the National Institutes of Health. Pinto disclosed receiving consulting fees from Sanofi/Regeneron, Optinose, and Genentech not related to this work.

https://www.medscape.com/viewarticle/978528

Regeneron's Dupixent and Eylea Offset Drop in COVID-19 Antibody Sales

 Regeneron Pharmaceuticals reported a 44% drop in revenue for the second quarter compared to the same period in 2021.

This overall drop was associated with sales of REGEN-COV, its antibody cocktail against COVID-19, banned in the U.S. in January, with a few exceptions, because it was ineffective against the Omicron variants. Otherwise, company sales were up 20%.

The real positive drivers were Eylea for chronic eye diseases and Dupixent for inflammatory conditions. Eylea climbed 14% to $1.62 billion. Since 2021, it has brought in $5.79 billion, an increase of 17% from the previous year.

In a note to investors, Wells Fargo analyst Mohit Bansal wrote, “We see 2Q22 results as representing a strong beat, with Eylea results showing a strong front against competition from [Roche’s] Vabysmo and continued momentum from Dupixent."

Dupixent sales jumped almost 40% to $2.09 billion for the second quarter.

“The second quarter of 2022 was distinguished by record net product sales of Eylea, Dupixent, and Libtayo, as well as multiple regulatory achievements for Dupixent, including U.S. approvals for atopic dermatitis among very young patients and for eosinophilic esophagitis in adults and adolescents, as well as European approval for pediatric asthma,” Dr. Leonard S. Schleifer, M.D., Ph.D., president and CEO of Regeneron, said. “In addition, we have continued to strengthen our oncology franchise, including through the purchase of worldwide rights to Libtayo as well as encouraging but preliminary anti-tumor activity observed at higher doses of our novel PSMAxCD28 costimulatory bispecific in combination with Libtayo for advanced metastatic castration-resistant prostate cancer.”

As is common with quarterly reports, Regeneron updated its pipeline, including terminating four clinical trials of REGEN-COV. The axed trials include a study of the antibody cocktail in high-risk patients 12 years and younger, a prevention trial in immunocompromised teens and adults, and a study in children hospitalized with COVID-19 and one for non-hospitalized patients. According to clinicaltrials.gov, the studies were terminated because of “emerging SARS-CoV-2 variants impacting susceptibility to study drug.”

Regeneron’s antibody therapy against COVID-19 wasn’t the only such treatment to lose the battle against variants and antiviral drugs. GlaxoSmithKline-Vir Biotechnology’s sotrovimab, as well as Eli Lilly’s bamlanivamab and etesevimab have shown less effectiveness against variants, resulting in modifications to their Emergency Use Authorizations and sales. Largely, they have been replaced by effective vaccines, such as Pfizer’s Paxlovid and Merck’s Lagevrio.

Regeneron has about 35 drugs in clinical development. 

The company’s collaboration revenue with Sanofi increased by 55% to $678 million for the quarter compared to the same period in 2021. Although they have pulled back on this somewhat in recent years, Regeneron has long been dubbed Sanofi’s “innovation engine.” The increase in revenue was related to shared profits from the commercialization of antibodies and higher Dupixent profits.

Regeneron’s R&D investments were $794 million for the quarter, and Selling, General, and Administrative (SG&A) were $475 million. The GAAP effective tax rate for the quarter was 11.5%, compared to 17.4% in the second quarter of 2021. This was primarily due to the proportion of income earned in foreign sales with lower tax rates than in the U.S.

GAAP net income per diluted share was $7.47 in the quarter, compared to $27.97 in the second quarter of 2021.

“We are pleased with our second quarter 2022 financial performance, including 20% revenue growth when excluding contributions from REGEN-COV. This demonstrates the continued strength of our core business,” Robert E. Landry, executive vice president, Finance, and CFO of Regeneron, said. “Additionally, we updated our full-year 2022 financial guidance primarily to reflect the recently completed acquisition of Libtayo global rights from Sanofi, a transaction that we believe will deliver significant shareholder value over time. In the second half of 2022, we look forward to advancing our pipeline with important clinical data readouts in oncology and ophthalmology as well as continued commercial execution and prudent capital allocation to drive value creation for shareholders.”

https://www.biospace.com/article/regeneron-q2-dupixent-and-eylea-set-off-drop-in-covid-19-antibody-sales/