Category: New Compounds and Treatments

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

An End to The ‘Therapeutic Drought’ in Atopic Dermatitis

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Source: NCI

The end of a longstanding “therapeutic drought” in atopic dermatitis (AD) is in sight as improved understanding of the pathogenesis and pathophysiology has stoked development of multiple drug candidates, according to a leading expert in the field.

“We did have treatments like cyclosporine, that are not specific as we know, and they are not treatments we can give our patients for long-term disease control,” said Emma Guttman-Yassky, MD, of the Icahn School of Medicine at Mount Sinai, during the Inflammatory Skin Diseases Summit.

She said that overcoming this drought was not easy, mostly because “we didn’t have enough understanding of the disease and its pathogenesis, really preventing therapeutic development for patients with atopic dermatitis,” she said.

New AD therapies built on the trail made for psoriasis treatment, starting with basic studies that produced insights into pathogenesis, leading to hypotheses that eventually could be tested in clinical trials, she said. Progress was accompanied by many failures in early stages of therapeutic development in psoriasis.

“One failure that I remember very vividly from psoriasis was the failure of interferon-gamma targeting,” Dr Guttman-Yassky recounted. “In atopic dermatitis, we also had our share of this type of failure, but these failures really helped shape therapeutic directions for all the diseases we are now targeting, including atopic dermatitis.”

This rocky development has led to recognition that AD is a complex disease involving multiple pathogenetic components, including barrier dysfunction, immune abnormalities, disruption of the dermal microbiome, and the peripheral and central nervous systems that play a central role in itch and other disease manifestations.

“Of all the major components involved in AD pathogenesis, immune targeting is the most tractable,” said Dr Guttman-Yassky. “Immune abnormalities are the most important because they perpetuate the disease phenotype of atopic dermatitis, from the nonlesional skin to acute disease and chronic lesions.”

In contrast to psoriasis, AD is a more heterogeneous disease with multiple clinical phenotypes that correlate with differences in immune polarisation and barrier dysfunction. All of the phenotypes exhibit activation of the type 2 inflammatory pathway as a common feature. Across the spectrum of clinical phenotypes, additional cytokine targeting may be required to achieve disease control.

Understanding that AD arises from systemic inflammation has also helped therapy development. Several studies have suggested that, compared to psoriasis, AD is associated with higher levels of immune activation. Blood samples of patients with AD have shown increased levels of activated T cells, circulatory cytokines, and cardiovascular markers.
The accumulation of new insights into AD pathogenesis added no fewer than a dozen viable therapeutic candidates to the pipeline. Dupilumab (Dupixent) led the way in providing the proof of principle that Th2-specific targeting reverses key pathogenetic factors that drive the disease process in AD.

Dr Guttman-Yassky pointed out how targeting Th2 inflammation with dupilumab led to reversal of barrier defects and lichenisation typical of AD as early as 4 weeks, and that by 16 weeks lesional and nonlesional skin looked similar. Furthermore, markers of epidermal hyperplasia and proliferation were “completely wiped out.”

Dr Guttman-Yassky highlighted several key classes of AD drug candidates with potential to build on the success of targeting inflammation: Interleukin-13 inhibition, OX40 inhibition and JAK/STAT inhibition, which showed promising results.

“With these types of response rates, our treatment goals for our patients are evolving,” said Dr Guttman-Yassky.

Source: MedPage Today

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

New Drug Targets for Memory Loss

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Image by Falkurian Design on Unsplash

Researchers have identified specific drug targets within memory-encoding neural circuits, opening up possibilities for new treatments of a range of brain disorders.

Memory loss is a main feature of a number of neurological and psychiatric disorders including Alzheimer’s disease and schizophrenia. Presently, there are few, very limited memory loss treatments and the search for safe and effective drug therapies has, until now, borne little fruit.

The research was done in collaboration with colleagues at the international biopharmaceutical company Sosei Heptares. The findings, published in Nature Communications, identify specific receptors for the neurotransmitter acetylcholine that re-route information flowing through memory circuits in the hippocampus. Acetylcholine is released in the brain during learning and is critical for the acquisition of new memories. Until now, the only effective treatment for the symptoms of cognitive or memory impairment seen in diseases such as Alzheimer’s is using drugs that broadly boost acetylcholine. However, this leads to multiple adverse side effects. The discovery of specific receptor targets that have the potential to provide the positive effects whilst avoiding the negative ones is promising.

Lead author Professor Jack Mellor from the University of Bristol’s Center for Synaptic Plasticity, said: “These findings are about the fundamental processes that occur in the brain during the encoding of memory and how they may be regulated by brain state or drugs targeting specific receptor proteins. In the long-term, the discovery of these specific targets opens up avenues and opportunities for the development of new treatments for the symptoms of Alzheimer’s disease and other conditions with prominent cognitive impairments. The academic-industry partnership is important for these discoveries and we hope to continue working together on these projects.”

Dr Miles Congreve, Chief Scientific Officer at Sosei Heptares, added: “These important studies have helped us to design and select new, exquisitely targeted therapeutic agents that mimic the effects of acetylcholine at specific muscarinic receptors, without triggering the unwanted side effects of earlier and less-well targeted treatments. This approach has the exciting potential to improve memory and cognitive function in patients with Alzheimer’s and other neurological diseases.”

“It is fascinating how the brain prioritises different bits of information, working out what is important to encode in memory and what can be discarded. We know there must be mechanisms to pull out the things that are important to us but we know very little about how these processes work. Our future program of work aims to reveal how the brain does this using acetylcholine in tandem with other neurotransmitters such as dopamine, serotonin and noradrenaline,” said Professor Mellor.

Source: University of Bristol

Categories : New Compounds and Treatments Pain ManagementTags :

Breakthrough Could Lead to New Opioid Alternatives

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Source: NCI on Unsplash

Monash University researchers have made a breakthrough discovery that might lead to new non-opioid analgesics to treat neuropathic pain safely and effectively, without the risk of opioid addictions.

Neuropathic pain occurs when nerves are damaged or dysfunctional, and can be caused by injury, virus infection or cancer treatment, or it can be a symptom or complication of conditions such as multiple sclerosis and diabetes.

The new study, published in Nature, has shown a new mode of targeting the adenosine A1 receptor protein, which had long been a promising therapeutic target for non-opioid painkillers to treat neuropathic pain. However, development of analgesics using it had failed due to a lack of sufficient on-target selectivity, as well as undesirable adverse effects.

In the study, Monash researchers used electrophysiology and preclinical pain models to show that a particular class of molecule, called a ‘positive allosteric modulator’ (PAM), can enhance the targeting of the A1 receptor by binding to a different region of the protein.

Another breakthrough in the study was observing the high-resolution structure of the A1 receptor bound to both its natural activator, adenosine, and an analgesic PAM, which was facilitated by the application of cryo electron microscopy (cryoEM), providing the first atomic level snapshot of the drug binding location.

Chronic pain remains a widespread global health burden. A lack of treatment options has led to over-reliance on opioid painkillers, which provide only limited relief in patients with chronic (particularly neuropathic) pain, while having severe adverse effects, such as respiratory depression and addiction. In 2016, 42 000 deaths related to opioid misuse were recorded in the US, while 25 million Americans suffer from chronic pain.

This new discovery opens the door to the development of non-opioid drugs that lack such side effects.

Co-corresponding author of the study and Dean of the Faculty of Pharmacy and Pharmaceutical Sciences, Professor Arthur Christopoulos said: “The world is in the grip of a global opioid crisis and there is an urgent need for non-opioid drugs that are both safe and effective.”

Source: Monash University

Categories : New Compounds and TreatmentsTags :

New Molecules Provide Deeper UV Protection

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Two new molecules that release tiny quantities of hydrogen sulfide have been found to prevent skin from ageing after being exposed to ultraviolet light found in sunlight. The study was published in Antioxidant and Redox Signalling.

For the study, the researchers exposed adult human skin cells and the skin of mice to ultraviolet radiation (UVA). UVA causes skin ageing by turning on collagenases, enzymes which eat away at the natural collagen, causing the skin to lose elasticity, sag and wrinkle. UVA also penetrates deeper into skin than the UV radiation that causes sunburns (UVB), and it also damages cellular DNA, leading to mutations that can contribute to some skin cancers. Typical sun creams sit on top of the skin and absorb UV radiation, but they do not penetrate the skin where the long-lasting damage occurs.

For deeper protection, the researchers came up with a new way to protect the deeper layers of skin using two compounds invented at the University of Exeter: AP39 and AP123. The compounds do not protect the skin in the same way traditional sun creams prevent sunburn, but instead penetrate the skin to correct how skin cells’ energy production and usage was turned off by UVA exposure. This then prevented the activation of skin-degrading collagenase enzymes. 

The compounds used in this study were previously shown to have impressive effects in reducing skin inflammation and skin damage after burn injury and atopic dermatitis (eczema). In an anti-ageing context, they prevented human skin cells in test tube experiments from ageing, but this is the first time the effects of photo-ageing have been seen in animals.

The important observation noted was that the compounds only regulated energy production, PGC-1α and Nrf2 in skin that was exposed to UVA. This suggests a novel approach to treating skin that has already been damaged by UV radiation, and could potentially reverse, as well as limit, that damage.

While further research is needed, there could be medical as well as cosmetic implications from this work, where protecting skin from UV light is important. For example, not only premature skin ageing and skin cancers, but UV light allergies, solar urticaria and rare hereditary skin diseases such as xeroderma pigmentosum. The researchers are currently partway through testing newer and more potent molecules able to do the same task using newer approaches.

Source: University of Exeter

Categories : New Compounds and TreatmentsTags :

New Lupus Treatment Gets the Nod from FDA

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Source: Unsplash

AstraZeneca announced that its type 1 interferon receptor antagonist anifrolumab (Saphnelo) has received approval from the US Food and Drug Administration for the treatment of moderate-to-severe systemic lupus erythematosus alongside standard therapy.

“This is wonderful, exciting news, and is great for the lupus community — patients, family members, and clinicians who treat patients,” said Richard Furie, MD, chief of rheumatology at Northwell Health in Great Neck, New York, in an interview.

Only belimumab (Benlysta) in 2011 and voclosporin (Lupkynis) for lupus nephritis a few months ago had been approved in the past decades. “And that represents 25 years of trying,” Dr Furie said.

Significant benefits were reported in 2016 in a phase IIb trial known as MUSE. In that trial, 62.6% of patients receiving 300 mg intravenous anifrolumab every 4 weeks had an SLE Responder Index score of 4 (SRI-4) plus a reduction in the steroid dose to less than 10 mg/day compared with only 17.6% of patients in the placebo group, which was a significant difference — the best lupus trial data so far, according to Dr Furie.

Two pivotal phase III trials, TULIP-1 and TULIP-2, followed, with conflicting results.

In TULIP-1, the primary endpoint of Systemic Lupus Erythematosus Responder Index (SRI-4) was not met. After a year, an SRI-4 response was seen in 36% of patients receiving anifrolumab and in 40% on placebo. Some secondary endpoints suggested benefits, including the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA).

In TULIP-2, patients were randomised 300 mg intravenous anifrolumab or placebo every 4 weeks for 48 weeks, with a BICLA response as the primary endpoint. After a year, 47.8% of patients in the anifrolumab group achieved a BICLA response compared with 31.5% of placebo patients.

“We were all shocked when TULIP-1 failed,” said Dr Furie, who is also a leading member of the Lupus Research Alliance’s Lupus Clinical Investigators Network. “But it didn’t really fail — it depends on how you define failure. It did not reach the primary endpoint, but on the other composite, BICLA, it was successful, as well as on a lot of the key secondary endpoints. The totality of the data, I think, is the key phrase,” he said.

“I think the two studies were more similar than dissimilar. You have to have an appreciation of how difficult it is doing clinical trials in lupus. For every one trial that has been successful, there have probably been 10 that were unsuccessful,” he said.

This was not the first time discordant results had been seen in lupus trials. “We also saw discordance between the BICLA and SRI in the ustekinumab phase II trial,” he noted.

Source: MedPage Today

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

A Treatment for Heart Attack from Spider Venom

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Photo by Adrián Valverde on Unsplash
Photo by Adrián Valverde on Unsplash

A protein found in the venom of one of the world’s deadliest spiders has been shown to preserve heart cells, and could be developed into a potentially life-saving treatment for heart attack victims.

A drug candidate developed from a molecule found in the venom of the Fraser Island (K’gari) funnel web spider can prevent damage caused by a heart attack and extend the life of donor hearts used for organ transplants. This would not be the first investigation into a clinical application for spider venom, however. Tarantula spider venom has also been investigated as a potent anaesthetic.

The discovery was made by a team led by Dr Nathan Palpant and Professor Glenn King from The University of Queensland (UQ) and Professor Peter Macdonald from the Victor Chang Cardiac Research Institute.

Dr Palpant, from UQ’s Institute for Molecular Bioscience (IMB), said the drug candidate worked by stopping a ‘death signal’ sent from the heart in the wake of an attack.

“After a heart attack, blood flow to the heart is reduced, resulting in a lack of oxygen to heart muscle,” Dr Palpant said. “The lack of oxygen causes the cell environment to become acidic, which combine to send a message for heart cells to die.

“Despite decades of research, no one has been able to develop a drug that stops this death signal in heart cells, which is one of the reasons why heart disease continues to be the leading cause of death in the world.”

Using beating human heart cells exposed to heart attack stresses, Dr Palpant tested the drug candidate, a protein called Hi1a, to see if the drug improved the cells’ survival.

“The Hi1a protein from spider venom blocks acid-sensing ion channels in the heart, so the death message is blocked, cell death is reduced, and we see improved heart cell survival.”

At present, there are no drugs in clinical use that prevent the damage caused by heart attacks.

Professor Macdonald of Victor Chang Cardiac Research Institute said that this incredible result had been decades in the making.

“This will not only help the hundreds of thousands of people who have a heart attack every year around the world, it could also increase the number and quality of donor hearts, which will give hope to those waiting on the transplant list,” said Professor MacDonald, who is also a senior cardiologist at St Vincent’s Hospital in Sydney.

“The survival of heart cells is vital in heart transplants — treating hearts with Hi1a and reducing cell death will increase how far the heart can be transported and improve the likelihood of a successful transplant,” added Prof MacDonald. “Usually, if the donor heart has stopped beating for more than 30 minutes before retrieval, the heart can’t be used — even if we can buy an extra 10 minutes, that could make the difference between someone having a heart and someone missing out. For people who are literally on death’s door, this could be life-changing.”

The discovery builds on earlier work by Professor King, who identified a small protein in the venom of the Fraser Island (K’gari) funnel-web spider that was shown to markedly improve recovery from stroke.

“We discovered this small protein, Hi1a, amazingly reduces damage to the brain even when it is given up to eight hours after stroke onset,” Professor King said.

“It made sense to also test Hi1a on heart cells, because like the brain, the heart is one of the most sensitive organs in the body to the loss of blood flow and lack of oxygen.

“For heart attack victims, our vision for the future is that Hi1a could be administered by first responders in the ambulance, which would really change the health outcomes of heart disease.”

“This is particularly important in rural and remote parts of Australia where patients and treating hospitals can be long distances apart — and when every second counts.”

Also, this could help for the transfer of donor hearts for cardiac transplantation — allowing these donor hearts to be transported over longer distances and therefore increasing the network of available donors and recipients.

The protein has been tested in human heart cells, and the team are aiming for human clinical trials for both stroke and heart disease within 2-3 years.

Source: ScienceDaily

Journal information: Meredith A. Redd, et al. Therapeutic Inhibition of Acid Sensing Ion Channel 1a Recovers Heart Function After Ischemia-Reperfusion Injury. Circulation, 2021; DOI: 10.1161/CIRCULATIONAHA.121.054360

Categories : New Compounds and TreatmentsTags :

Immunotoxin Treatment Stops Liver Fibrosis

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A microscopic image of liver tissue affected by non-alcoholic fatty liver disease (NAFLD). The large and small white spots are excess fat droplets filling liver cells (hepatocytes). Credit: Dr. David Kleiner, National Cancer Institute/NIH
A microscopic image of liver tissue affected by non-alcoholic fatty liver disease (NAFLD). The large and small white spots are excess fat droplets filling liver cells (hepatocytes). Credit: Dr David Kleiner, National Cancer Institute/NIH

A new study successfully used immunotoxins to prevent the progression of liver fibrosis by targeting a protein specific to that disease.

Fibrosis, the buildup of collagen and scar tissue, can be caused by alcohol abuse and disease. University of California San Diego School of Medicine researchers and their collaborators are looking for ways to treat fibrosis by preventing liver cells from producing collagen. 

“So we thought…what if we take immunotoxins and try to get them to kill collagen-producing cells in the liver,” explained team lead Tatiana Kisseleva, MD, PhD, associate professor of surgery at UC San Diego School of Medicine. “If these antibodies carrying toxic molecules can find and bind the cells, the cells will eat up the ‘gift’ and die.”

The study focussed on immunotoxins designed to bind a protein called mesothelin, which is rarely found in the healthy human body. The protein is only produced by cancer cells and collagen-producing liver cells, known as portal fibroblasts.

Kisseleva teamed up with co-author Ira Pastan, MD, at the National Cancer Institute, part of the National Institutes of Health (NIH). Dr Pastan is co-discoverer of mesothelin and an expert on using immunotoxins to target the protein on cancer cells, and he leads several clinical trials using it in treating patients with ovarian cancer, mesothelioma and pancreatic cancer.

Since the immunotoxins specifically recognise human mesothelin, the researchers couldn’t use a traditional mouse model of liver fibrosis. So, they transplanted human liver cells isolated from patients to mice and treated them with the anti-mesothelin immunotoxin. Compared to untreated mice, 60 to 100 percent of human mesothelin-producing cells were killed by the immunotoxins, which also reduced the deposition of collagen.

Liver fibrosis treatment is very limited at present, with weight loss being currently the only known method for reducing liver fibrosis associated with non-alcoholic fatty liver disease. Alcoholic liver disease is most commonly treated with corticosteroids, but they are not highly effective. Early liver transplantation is the only proven cure, but it is rarely available.

“What we want to know now is, can this same strategy be applied to other organs?” Dr Kisseleva said. “Surprisingly enough, the same cells are responsible for fibrosis in the lung and kidneys. This is especially exciting because we already know from Dr Pasten’s cancer clinical trials that anti-mesothelin immunotoxins are safe in humans, potentially speeding up their application in other areas.”

The findings were published in Proceedings of the National Academy of Sciences

Source: University of California San Diego

Journal information:Nishio, T., et al. (2021) Immunotherapy-based targeting of MSLN+ activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis. PNAS. doi.org/10.1073/pnas.2101270118. 

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

Probe over Controversial Alzheimer’s Drug’s Approval

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Amyloid plaques and neurons. Source: NIAH

The interim commissioner of the US Food and Drug Administration, Janet Woodcock, MD, last week requested the country’s Office of Inspector General to perform an independent investigation into the regulator’s decision to approve Biogen’s controversial Alzheimer’s drug Aduhelm.

Dr Woodcock noted in her letter that there “continues to be concerns raised” regarding the contact between FDA officials and Biogen ahead of the agency’s decision, “including some that may have occurred outside of the formal correspondence process.”

Dr Woodcock’s request comes after a bombshell report from Stat, which found that Biogen executives met with FDA officials, specifically Billy Dunn, MD, director of the FDA’s neuroscience unit, as early as 2019 to discuss a regulatory pathway for Aduhelm. The meetings took place even when it seemed there was no progress for the drug.

Earlier this week, a US House Representative, charged Biogen with “undue influence” over the FDA’s review process. Less than two weeks earlier, the House Committee on Oversight and Reform said it would conduct its own probe into the approval along with Biogen’s pricing strategies.

In the letter from Friday, Dr Woodcock said the agency would fully cooperate with the potential investigation to determine whether any of its interactions with Biogen were inconsistent with FDA policies and procedures.

“Given the ongoing interest and questions, today I requested that @OIGatHHS conduct an independent review and assessment of interactions between representatives of Biogen and FDA during the process that led to the approval of Aduhelm,” tweeted Dr Woodcock.

However, she maintained that she has “tremendous confidence” in the leadership at the FDA’s Center for Drug Evaluation and Research, which was involved in the review of Aduhelm.

“We believe this review and assessment will help ensure continued confidence in the integrity of FDA’s regulatory processes and decision-making,” Woodcock said in a tweet.

A spokesperson from Biogen told Fierce Pharma that the company would “of course” cooperate with “any inquiry in connection with a possible review of the regulatory process.”

The commissioner’s request is only the latest event in a bizarre and twisted story since the FDA’s Aduhelm approval just one month prior.

Facing fierce criticism of its wide-labelled approval, the FDA made the surprising move to narrow Aduhelm’s label last week Thursday, restricting the recommendation to just those with milder Alzheimer’s.

This comes after Biogen’s drug was essentially allowed access to the nation’s some 6 million Alzheimer’s patients. That decision was met with almost immediate pushback, as it was pointed out that the drug could overwhelm the payer budgets of most Alzheimer’s patients.

Source: Fierce Pharma

Categories : New Compounds and TreatmentsTags :

Harnessing Magnetic Fields to Produce Safer and Cheaper Medicines

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An image of ferrofluid reacting to a magnetic field. Photo by Etienne Desclides on Unsplash

By using magnetism to eliminate unwanted ‘mirror’ counterparts inherent to the production of certain medications, they could be made safer and produced more cheaply, according to new investigations underway at Texas A&M University.

Everyday drugs, such as ibuprofen, may have an inherent flaw in their molecular structure, pairing the active, beneficial ingredient with a potentially ineffective, or even toxic, ‘mirror’ counterpart, due to being of the wrong chirality, or structural twist. New research using electromagnetic fields could help keep the effective ingredients while eliminating the unwanted counterparts. Chirality is already an important consideration in the development of new drugs.

Dr. Shoufeng Lan, assistant professor in the J Mike Walker ’66 Department of Mechanical Engineering at Texas A&M University, is leading a team investigating the use of electromagnetic control over the synthesis of chiral compounds — a technique which could open up a host of applications including in the pharmaceutical industry.

“Mysteriously, all living organisms on the Earth consist of only left-handed amino acids and right-handed sugars, but not their mirrored counterparts,” Prof Lan said. “The phenomenon is the so-called homochirality of life and it is the ultimate form of asymmetric synthesis.”

Prof Lan gave the example of a human hand to demonstrate the concept of chirality, noting that if you created a mirror image of your hand, it could not be perfectly superimposed over the original.

By identifying a successful method of using asymmetrical synthesis to create new versions of structures for items like ibuprofen, Prof Lan said that improved versions of generic pharmaceuticals with reduced toxicity could be produced at a lower cost than currently available due to the current purification process.

However, to achieve success, the researchers will first need figure out how to implement this magnetic effect on asymmetric synthesis at practical temperatures. The effect is currently fairly weak, even using a powerful magnetic field or at a temperature as low as -268°C.

Prof Lan noted that the 2001 Nobel Prize in chemistry’s topic was addressing chirality, which uses an existing chiral object—a catalyst molecule—to transfer chirality to the desired mirror image form as the final product.

“This Nature Communications paper demonstrated a giant atomic-scale magneto-chiral effect that is orders of magnitude stronger,” Prof Lan said. “By applying this effect, it is arguably possible to master an asymmetric synthesis or asymmetric self-assembling.”

Prof Lan said his team’s research could revolutionise the field by creating a new iteration of biomedical, chemical and pharmaceutical applications. For example, by asymmetrically synthesising only the active component of racemic Lexapro (the most common medication in the US with more than 25 million prescriptions) the research might reduce the drug’s side effects.

“We anticipate that our demonstration could lead to the creation of chiral seeds at the atomic scale,” Prof Lan said. “Upon them, we hope to transfer the chirality using cutting-edge technologies, such as a metal-organic framework, to create chiral materials from nanoscales to macroscales.”

Source: Phys.org

Journal information: Shoufeng Lan et al, Observation of strong excitonic magneto-chiral anisotropy in twisted bilayer van der Waals crystals, Nature Communications (2021). DOI: 10.1038/s41467-021-22412-9

Categories : Metabolic Disorders New Compounds and TreatmentsTags :

‘Game-changing’ Weight Loss Drug Semaglutide Approved by FDA

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Image source: Neonbrand on Unsplash

The US Food and Drug Administration approved a ‘game changing’ weight loss drug called Wegovy (semaglutide) for chronic weight management in adults with obesity or overweight.

This injection is the first drug for chronic weight management in adults with general obesity or overweight to be approved since 2014. The drug is indicated for chronic weight management in patients with a body mass index (BMI) of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 or greater, and is to be used in conjunction with diet and exercise.

“Today’s approval offers adults with obesity or overweight a beneficial new treatment option to incorporate into a weight management program,” said John Sharretts, MD, deputy director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “FDA remains committed to facilitating the development and approval of additional safe and effective therapies for adults with obesity or overweight.”

Approximately 70% of American adults have obesity or overweight, and >67% of sub-Saharan Africans. This is a serious health issue linked to leading causes of death such as heart disease, stroke and diabetes, and also to increased risk of certain types of cancer. Losing 5% to 10% of body weight through diet and exercise has been associated with a reduced risk of cardiovascular disease in adult patients with obesity or overweight.

Wegovy works by mimicking a hormone called glucagon-like peptide-1 (GLP-1) that targets areas of the brain regulating appetite and food intake. The medication dose must be increased gradually over 16 to 20 weeks to 2.4 mg once per week to reduce gastrointestinal side effects.

The drug’s safety and efficacy were studied in four 68-week trials. Over 2600 patients received Wegovy for up to 68 weeks in these four studies and more than 1500 patients received placebo.

The largest placebo-controlled trial enrolled diabetes free adults with an average age of 46 years, and 74% of whom were female. The average body weight was 105 kg and average BMI was 38 kg/m2. Individuals receiving Wegovy lost an average of 12.4% of their initial body weight compared to individuals who received placebo. Another trial enrolled adults with type 2 diabetes. The average age was 55 years and 51% were female, with an average body weight of 100 kg and average BMI of 36 kg/m2. In this trial, individuals receiving Wegovy lost 6.2% of their initial body weight compared to the placebo group.

“The approval of Wegovy in the US brings great promise to people with obesity. Despite the best efforts to lose weight, many people with obesity struggle to achieve and maintain weight loss due to physiological responses that favour weight regain,” said Martin Holst Lange, executive vice president, Development at Novo Nordisk. “The unprecedented weight loss for an anti-obesity medication marks a new era in the treatment of obesity, and we now look forward to making Wegovy available to people living with obesity in the US”.

Unfortunately, the drug may be out of the reach of many people in need of it, with indications being that the medication may be charged at around US$1,300 a month.

Source: Food and Drug Administration