University of Debrecen

Novo Nordisk continues to list monlunabant in its midstage diabetes and obesity pipeline.\n Novo Nordisk’s cannabinoid CB1 receptor blocker has run into another problem. Months after sharing obesity data that left investors underwhelmed, the Danish drugmaker has reported the failure of a midphase diabetic kidney disease trial of the molecule.CB1 receptor blockade is an old idea—Sanofi won approval for a drug with the mechanism in 2006—but Novo identified Inversago Pharma as a company capable of realizing the potential of the approach. Novo acquired the Canadian biotech in a deal worth up to $1.1 billion in 2023. Since then, a mix of lackluster efficacy and concerning safety signals for monlunabant in obesity have taken the shine off the deal.The program took another hit Wednesday when Novo reported a phase 2 flop. Investigators randomized 254 diabetic kidney disease patients to receive one of two doses of monlunabant or placebo. After 16 weeks of once-daily dosing, people on the study drug did no better than their counterparts on placebo on a measure of kidney function. The result caused the trial to miss its primary endpoint.Reporting of mild to moderate neuropsychiatric side effects was more frequent with monlunabant than placebo. The safety data add to concerns that the molecule suffers from some of the same problems that held back CB1 blockers in the past. European authorities withdrew the approval of Sanofi’s CB1 obesity drug in 2009 after studies found it doubled the risk of psychiatric disorders. Novo is yet to share safety and efficacy data from the kidney disease trial, with the only other snippet in the disclosure being the detail that the most common adverse events were gastrointestinal and the vast majority of cases were of mild to moderate severity.Martin Holst Lange, M.D., Ph.D., the company’s executive vice president of development, told analysts on its financial call Wednesday morning that Novo wasn’t discouraged by the fail, pointing out that “we never did the acquisition of monlunabant to develop it purely for diabetic kidney disease—our focus was on the weight loss potential.”“Second, I just remind you that that that these are small studies, so obviously, we try to see them in the context of the full picture,” he said. “When we look at the safety and tolerability profile, it was comparable, albeit at a slightly lower rate than in the dedicated obesity study, basically indicating that we can still have an aspiration of exploring this further in phase 2b with lower doses, looking at weight loss potential, but obviously also—and this has been the intent from the get-go—ruling out a potential safety concern.”

Pictured: Illustration of red blood cells iStock, ismagilov Novo Nordisk and Ionis Pharmaceuticals unveiled promising respective data at the American College of Cardiology’s Annual Scientific Session, while Boehringer Ingelheim and Eli Lilly’s Jardiance missed the endpoint in a myocardial infarction study. The American College of Cardiology’s 73rd Annual Scientific Session & Expo (ACC24) took place over the weekend in Atlanta, spotlighting the latest and most impactful innovations in the field of cardiovascular care. BioSpace has highlighted below some of the most notable presentations from ACC’s Annual Scientific Session. Novo Builds Wegovy’s Cardio Case, Eyes Heart Failure Still riding high from winning its recent cardiovascular approval for Wegovy (semaglutide), Novo Nordisk is continuing its expansion into heart health with new promising data from its Phase III STEP-HFpEF study . At 52 weeks, patients treated with the blockbuster obesity drug saw a significantly greater reduction in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) versus placebo. Wegovy also outperformed the placebo group in terms of body weight reduction, six-minute walk distance and C-reactive protein levels. Taken together, these findings suggest that Wegovy could significantly ease symptomatic burden and physical limitations in patients with obesity, heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus. The GLP-1 treatment also boosted patients’ exercise function and weight loss. Results from the large Phase III trial, which randomized more than 600 patients, were also published on Friday in The New England Journal of Medicine . Novo previously posted heart failure findings for Wegovy, announcing in August 2023 that the weight-loss medication could significantly improve KCCQ-CSS scores in the Phase III STEP trial, which enrolled patients with obesity and HFpEF, but not diabetes. Novo has submitted data from these two studies to the FDA, seeking to expand Wegovy’s label to include HFpEF, STAT News reported. Ionis Moves Toward Rare Metabolic Disorder Approval Ionis Pharmaceuticals unveiled promising results from its Phase III BALANCE study at ACC24, showing that its investigational RNA-targeted antisense therapy olezarsen can reduce triglyceride levels in patients with familial chylomicronemia syndrome (FCS). At six months, patients treated with the 80-mg dose of olezarsen saw a 44% placebo-adjusted reduction in triglyceride levels, an effect that was statistically significant, with a p-value less than 0.001, according to Ionis. This effect continued and improved through 12 months, reaching a 59% placebo-adjusted reduction. Patients in the olezarsen arm also developed “markedly fewer” acute pancreatitis events over 12 months of follow-up. CEO Brett Monia in a statement said that these results from BALANCE support “the potential for olezarsen to be the standard of care for patients with FCS, if approved,” adding that the company is “working closely with the FDA” for olezarsen’s regulatory application, which Ionis expects to this year. Ionis in September 2023 revealed early data from BALANCE. At the time, olezarsen elicited a 100% reduction in acute pancreatitis events versus placebo. Olezarsen is an RNA-targeted ligand-conjugated antisense treatment that works by lowering the body’s production of the apoC-III protein, which is produced in the liver and is involved in the regulation of triglycerides in the blood. Aside from FCS, Ionis is also studying the candidate in severe hypertriglyceridemia. Boehringer, Lilly’s Jardiance Misses in Myocardial Infarction Data from Boehringer Ingelheim and Eli Lilly ’s Phase III EMPACT-MI trial showed that their SGLT2 inhibitor Jardiance (empagliflozin) does not significantly reduce the risk of heart failure hospitalization or death from any cause in patients who had suffered an acute myocardial infarction (MI) episode. At a median follow-up of 17.9 months, 267 patients in the Jardiance arm developed the composite primary endpoint of being hospitalized for heart failure or dying from any cause. This figure corresponds to a rate of 8.2%, whereas the primary outcome arose in 9.1% of those patients in the placebo arm. The between-group difference did not reach statistical significance, with a p-value of 0.21, according to the ACC’s news release on the results. However, disaggregating the primary endpoint into its components showed that Jardiance could significantly lower the risk of a first hospitalization for heart failure by around 23% versus placebo. EMPACT-MI lead author Javed Butler in a statement said that Jardiance “did not reduce mortality after a heart attack, but did reduce the risk of heart failure after heart attack,” adding that this “25% to 30% reduction” in heart failure hospitalizations is “pretty clinically meaningful.” Jardiance also failed to elicit significant improvements in EMPACT-MI’s key secondary endpoints. An exploratory analysis also found no benefit on cardiovascular death, time to death from cardiovascular causes, as well as time to first heart failure hospitalization or cardiovascular death. Arrowhead Shoots for Pivotal SHTG Study for Candidate Arrowhead Pharmaceuticals unveiled Phase IIb data for its investigational RNAi therapy plozasiran at ACC24, demonstrating steep triglyceride reductions at 24 weeks in patients with severely elevated triglyceride levels who are at risk of developing acute pancreatitis. In the mid-stage SHASTA-2 trial, Arrowhead’s asset reduced triglyceride levels by 74% while placebo only elicited a 17% decrease. Plozasiran also met the study’s key secondary endpoint, with its highest doses triggering a 58% average drop in triglyceride at 48 weeks versus 7% in the placebo group. ApoC3, a liver protein that disrupts the clearance of fats from the body, was lowered by 48% among plozasiran-treated patient at 48 weeks. Placebo comparators, meanwhile, saw a 4% increase in ApoC3 at this time point. SHASTA-2 lead author Daniel Gaudet said in a statement that these findings “support the initiation of pivotal studies of plozasiran for the treatment of severe hypertriglyceridemia.” Plozasiran is an investigational RNAi therapeutic that works by interrupting the expression of the ApoC3 gene, resulting in overall lower levels of the protein. This mechanism of action could block the pathologic function of ApoC3 and help normalize lipid levels in patients, according to Arrowhead’s website . Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com .

More than 1 million Hungarians could experience tinnitus Tinnitus Klinika's 3 clinics will provide Lenire throughout Hungary Availability in Hungary follows publication of second large-scale clinical trial results, showing greater improvement in tinnitus symptoms BUDAPEST, Hungary, Sept. 29, 2022 /PRNewswire/ -- Irish medical device company, Neuromod Devices Ltd., which specialises in the treatment of tinnitus, has reached an agreement with Tinnitus Klinika kft, a provider of specialist tinnitus care, to make its Lenire device available in Hungary. Continue Reading Tamás Nagy, CEO & Owner of Tinnitus Klinika Tinnitus patient using Lenire Lenire is a bimodal neuromodulation device which has shown in analysis of real-world patients and multiple large-scale clinical trials to reduce the severity of tinnitus symptoms. Tinnitus, commonly known as "ringing in the ears", is a complex neurological condition resulting in the perception of sound without an external source. Landmark research into the prevalence of tinnitus in Europe was published in renowned scientific journal, The Lancet, in late 2021. It found that prevalence of any tinnitus was 14.7%i, which could mean that 1.4 million Hungarians experience the condition. Through this distribution agreement, Tinnitus Klinika's specialist team has exclusive licence from Neuromod to provide Lenire throughout Hungary to suitable patients for the treatment of their tinnitus. "I'm delighted to work with Tinnitus Klinika to make Lenire available to people living with tinnitus in Hungary. Tinnitus is globally recognised as a significant healthcare challenge and many people living with the condition have unmet clinical needs. Tinnitus specialists like Tinnitus Klinika deeply understand the needs of tinnitus patients and we're proud to be able to support them in improving therapeutic outcomes for their patients," explains Dr Ross O'Neill, Founder and CEO of Neuromod Devices. In the last 12 months Neuromod has expanded availability of Lenire in Europe, launching it in Denmark, Norway, Spain, Switzerland, and the UK. Earlier in 2022 the results of an independent real-world analysis were published in the peer-reviewed scientific journal, Brain Stimulation, demonstrating the safety and efficacy of the Lenire device for improving symptoms in tinnitus patients. The study found that 85% of tinnitus patients experienced a reduction in their tinnitus symptoms, as measured by THIii, following six to 12 weeks of treatment using Lenireiii. The device has also been used in large-scale clinical trials with over 500 patients. In June, the results of Lenire's second large-scale clinical trial were published in the highly regarded scientific journal, Nature – Scientific Reports. They showed a significant further breakthrough for improving tinnitus symptoms severity with Lenireiv. By changing the stimuli patients received halfway through their treatment plan, a clinically significant greater average improvement in tinnitus symptom severity was demonstratediv. 95% of treatment-compliant participants reported an improvement in their tinnitus symptoms, as measured by THIii,iv. 91% of treatment-compliant participants reported an improvement which sustained at least up to 12 months after treatment had endediv. Tinnitus Klinika's team have been providing specialist care for people living with tinnitus since it was founded in 2008 by Tamás Nagy, who holds a degree in Audiology from Oxford-Brookes University. The organisation operates 3 clinics in Hungary at Czeizel Institute in Budapest, Hallomás Center in Veszprém, and at Debrecen University in partnership with the University's Medical school. Tinnitus Klinika offers a suite of therapeutic interventions for people with tinnitus, which now includes Lenire, and has facilitated research of these interventions in their clinical practices under the guidance of the organisation's Advisory Board. "Tinnitus Klinika's partnership with Neuromod is a significant step forward for our tinnitus patients. I'm delighted to be able to provide an evidence-based treatment option that has seen encouraging patient outcomes in large-scale clinical trials and in the real world as part our suite of services for people living with the condition. I'm looking forward to working closely with Neuromod's team to achieve the best possible patient outcomes in our clinics ," explains Tamás Nagy, CEO at Tinnitus Klinika. Lenire is a bimodal neuromodulation device which combines mild electrical pulses to the tongue with sound stimulation to drive neuroplasticity in the brain which reduces the symptoms of tinnitus. It has CE-mark certification for the treatment of tinnitus under the supervision of an appropriately qualified healthcare professional and is currently available throughout Europe. The device consists of Bluetooth® headphones which play customised sounds to activate the auditory nerve, a proprietary intra-oral device which provides mild electrical stimulation to the surface of the tongue, known as a Tonguetip®, and a controller which controls the duration and intensity of treatment with the device. The device's sound and electrical stimuli can be calibrated to suit a patient's tinnitus after an initial assessment of their condition which includes an audiological exam. The supervising healthcare professional demonstrates how to use the device and provides the patient with instructions for use. Subsequently, patients use Lenire for 60 minutes per day typically for at least 10 weeks. Follow-up visits with the healthcare professional occur during treatment to monitor patients' progress. At the end of the prescribed treatment plan, the healthcare professional advises the patient about their continued use of Lenire. For more information please contact: Neil Doyle Global Director of Marketing, Neuromod Devices [email protected] About Neuromod Devices Ltd Founded in 2010, Neuromod Devices Ltd. is a medical technology company headquartered in Dublin, Ireland. Neuromod specialises in the design and development of neuromodulation technologies to address the clinical needs of underserved patient populations who live with chronic and debilitating conditions. The lead application of Neuromod's technology is in the field of tinnitus, where Neuromod has completed extensive clinical trials to confirm the efficacy of its non-invasive neuromodulation platform in this common disorder. Neuromod's tinnitus treatment device, Lenire, is currently available throughout Europe. For more information visit . About Tinnitus Klinika kft Tinnitus Klinika kft, established in 2008, is a provider of specialist tinnitus care operating 3 clinics throughout Hungary at Czeizel Institute in Budapest, Hallomás Center in Veszprém, and at Debrecen University. Tinnitus Klinika provides a range of treatment interventions for people living with tinnitus. About Lenire Lenire is the first non-invasive bimodal neuromodulation tinnitus treatment device shown to soothe and relieve tinnitus in a large-scale clinical trial. Lenire has CE-mark certification for the treatment of tinnitus under the supervision of an appropriately qualified healthcare professional in Europe. Further details about Lenire including a list of providers can be found at . References (i) R. Biswas et al., Tinnitus prevalence in Europe: a multi-country cross-sectional population study, The Lancet Regional Health (2021), (ii) THI or Tinnitus Handicap Inventory is a clinical standard for measuring the impact of tinnitus on someone's day-to-day life. Measured on a scale of 100, the higher the score, the greater the impact of tinnitus. Reducing a person's THI score should correspond to improved quality of life by reducing how their tinnitus is affecting them. (iii) Buechner A, Lesinski-Schiedat A, Becker P, Lenarz T, Real-world clinical experience with bimodal neuromodulation for the treatment of tinnitus - A case series, Brain Stimulation (2022), doi: . (iv) Conlon et al., Different bimodal neuromodulation settings reduce tinnitus symptoms in a large randomized trial, Sci Rep, (2022) Photo: Photo: SOURCE Neuromod Devices Ltd