Semaglutide (Novo Nordisk)

Bagsværd, Denmark, 25 July 2024 – Novo Nordisk today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for an update of the Wegovy® (semaglutide 2.4 mg) label to reflect data from the SELECT cardiovascular outcomes trial, demonstrating a risk reduction of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal heart attack (myocardial infarction) or non-fatal stroke in adults with established cardiovascular disease (CVD) and either overweight or obesity (initial BMI ≥27 kg/m2) without diabetes. The SELECT trial demonstrated that Wegovy® statistically significantly reduced the risk of MACE by 20% compared to placebo when added to standard of care. In addition, the findings from SELECT showed that over a period of up to five years, risk reductions in MACE were achieved regardless of baseline age, sex, race, ethnicity, body mass index (BMI) and level of renal function impairment. The exact mechanism of cardiovascular risk reduction has not been established but is likely multifactorial. “We believe that the recommendation to update the EMA label for Wegovy® is a significant milestone for people living with cardiovascular disease and obesity. The SELECT data demonstrated that in addition to helping people manage their weight, Wegovy® has the potential to protect lives by reducing the risks of major adverse cardiovascular events”, said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk. The label update also includes data from the SELECT trial showing a risk reduction in cardiovascular death by 15%, a risk reduction of death from any cause by 19%, and an 18% risk reduction in a heart failure composite endpoint, comprised of cardiovascular death, urgent heart failure visits and hospitalisations for heart failure, all compared to placebo1. Following the positive opinion from the CHMP, Novo Nordisk expects implementation of the label update within approximately one month. About obesity and cardiovascular disease Obesity is a chronic disease that requires long-term management. It is associated with many serious health consequences and decreased life expectancy. Obesity-related complications are numerous and include type 2 diabetes, chronic kidney disease, non-alcoholic fatty liver disease, cancer and an increased risk of CVD, including heart attack and stroke, high levels of blood sugar, cholesterol, blood pressure and inflammation. About the SELECT trial SELECT was a randomised, double-blind, parallel-group, placebo-controlled trial designed to evaluate the efficacy of Wegovy® versus placebo as an adjunct to standard of care for prevention of MACE in people with established CVD with overweight or obesity with no prior history of diabetes. People included in the trial were aged ≥45 years with a BMI ≥27 kg/m2 and were followed for a period of up to five years. The primary objective of the SELECT trial was to demonstrate the superiority of Wegovy® compared to placebo with respect to reducing the incidence of three-point MACE consisting of cardiovascular death, non-fatal heart attack (myocardial infarction) or non-fatal stroke. Key secondary objectives were to compare the effects of Wegovy® to placebo regarding mortality, heart failure, cardiovascular risk factors, including glucose metabolism, body weight and kidney function. The trial enrolled 17,604 adults and was conducted in 41 countries at more than 800 investigator sites. SELECT was initiated in 2018 and completed in 2023 About Wegovy® (semaglutide 2.4 mg)In the EU, Wegovy® is indicated as an adjunct to a reduced calorie diet and increased physical activity for weight management in adults with a BMI of 30 kg/m2 or greater (obesity), or adults with a BMI of 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition. In the EU, Wegovy® is also indicated for paediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater for age and gender (obesity) and body weight above 60 kg. In the US, Wegovy® is indicated in combination with a reduced calorie diet and increased physical activity to reduce the risk of MACE in adults with established cardiovascular disease and either obesity or overweight, as well as to reduce excess body weight and maintain weight reduction long term in adults and paediatric patients aged 12 years and older with obesity and in adults with overweight in the presence of at least one weight-related comorbid condition. About Novo NordiskNovo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 66,000 people in 80 countries and markets its products in around 170 countries. Novo Nordisk's B shares are listed on Nasdaq Copenhagen (Novo-B). Its ADRs are listed on the New York Stock Exchange (NVO). For more information, visit novonordisk.com, Facebook, Instagram, X, LinkedIn and YouTube. Contacts for further information Media: Ambre James-Brown +45 3079 9289abmo@novonordisk.comLiz Skrbkova (US)+1 609 917 0632lzsk@novonordisk.comInvestors: Jacob Martin Wiborg Rode+45 3075 5956jrde@novonordisk.comDavid Heiberg Landsted +45 3077 6915 dhel@novonordisk.comSina Meyer +45 3079 6656 azey@novonordisk.comFrederik Taylor Pitter +45 3075 8259 fptr@novonordisk.comIda Schaap Melvold +45 3077 5649 idmg@novonordisk.comMark Joseph Root (US) +1 848 213 3219mjhr@novonordisk.com Company announcement No 55 / 2024 1Cardiovascular death superiority not confirmed (hazard ratio: 0.85; 95% CI (0.71;1.01)). Death by any cause not statistically significant based on the prespecified testing hierarchy (hazard ratio: 0.81; 95% CI: (0.71; 0.93)). Composite heart failure (cardiovascular death, urgent heart failure visits and hospitalisations) not statistically significant based on the prespecified testing hierarchy (hazard ratio: 0.82; 95% CI: (0.71; 0.96)). Attachment PR240725-SELECT-CHMP-opinion

Partnering could be an option for Viking Therapeutics, although CEO Brian Lian, Ph.D., was unwilling to give away too much on any ongoing or previous discussions. Viking Therapeutics will launch a longship into phase 3 for the obesity drug VK2735 sooner than expected, with a clinical program expected to top $300 million.   The biotech—which was launched into the middle of the next-generation obesity medicine debate on the strength of weight loss data released earlier this year—has received the FDA’s blessing to begin planning a late-stage trial. CEO Brian Lian, Ph.D., told investors Wednesday afternoon that the company took results from the phase 2 VENTURE trial to the agency to plan the next steps for VK2735. The FDA provided written feedback, which is allowing Viking to move forward with plans for the key study. As for what that trial might look like, Lian was fairly mum, deferring detailed design questions until a later time during the earnings call. Lian said the FDA has not actually provided guidance on the phase 3 trial design just yet. The meeting was more to see whether Viking could proceed into late-stage trials at this time. “One of the primary goals of that dialogue was to understand if we were okay to go forward into phase 3 and we feel based on the feedback that we are okay to go forward,” Lian said. The next steps will be to schedule an end of phase 2 meeting with the FDA to review development plans, which Lian said should take place in the fourth quarter. But Lian did say that guidance from the FDA requires two phase 3 studies with a minimum of 4,500 people and at least 3,000 of them receiving the drug. He said “we would be looking to the guidance for the overall design strategy.” Chief Financial Officer Greg Zante expects the phase 3 registrational program for subcutaneous VK2735 to cost about $300 million. Pressed for more details, Zante said that figure does not include any additional outcomes studies such as a trial zeroing in on possible cardiovascular benefits. That’s where Big Pharmas like Eli Lilly and Novo Nordisk are heading as they attempt to show the broad health benefits of the GLP-1 therapies that have taken the world by storm. Novo recently received an FDA approval to use Wegovy to cut cardiovascular risks in adults with obesity, while Lilly is chasing an FDA approval for Zepbound in sleep apnea. The ability of major pharmaceutical companies like Lilly and Novo to conduct massive clinical programs underscores the challenges ahead for a small biotech like Viking. But the company has at least one trick up its sleeve. Lian said Viking is planning to explore whether subcutaneous VK2735 can be dosed monthly, which would be an improvement over the currently available weekly injections. “We believe the flexibility afforded by offering both a weekly and a monthly regimen should provide an attractive option for patients who wish to tailor dosing to their individual lifestyle and preference,” Lian said. The trial design will be revealed later, he added. Lian detailed the work going on to advance the oral tablet formulation of VK2735. Viking revealed in March that the candidate was advancing to phase 2 after achieving weight loss of 5% or more after just 28 days of dosing. “We believe a tablet formulation could represent an attractive treatment option for patients who are hesitant to initiate injection-based therapy, or for those seeking to maintain the weight loss they have already achieved,” Lian said. He envisioned a future where patients initially take the injectable formulation, then switch over to the pill after achieving weight loss. This would keep the patient on the exact same molecule rather than switching to a new medicine entirely and having to go through safety or tolerability challenges. Lian said Viking filed an investigational new drug application with the FDA in the second quarter to bring dosing in the phase 1 study of oral VK2735 to the U.S. He said this should speed study progression. With the application approved, Viking has already completed dose escalation for cohorts of patients taking 60 mg or 80 mg daily. Elsewhere, a 100-mg group is ongoing. The early data from the phase 1 trial already support moving into a larger phase 2 test, which Viking plans to initiate in the fourth quarter of this year, Lian said.   Small but mighty   Being a small biotech, a question on analysts' minds was whether Viking will go it alone with all these programs. The company has also been the subject of M&A murmurs, given Big Pharma's interest in the space. Lian said partnering could be an option, but he was unwilling to give away too much on any ongoing or previous discussions. “We've been consistent with our receptivity to interest and opportunities, and we remain so. In the meantime, we are well capitalized and focused on execution of the development programs,” Lian said. “In our view, continued execution will continue to add value to the pipeline. I think that is all we can say at this point.” Viking had cash and equivalents of $942 million as of June 30 compared to just $362 million at the end of 2023. Beyond the VK2735 subcutaneous program, Viking is working on the oral version, VK2809 for metabolic dysfunction-associated steatohepatitis (MASH), VK0214 in X-linked adrenoleukodystrophy (X-ALD) and other early weight loss programs. William Blair analysts expect this cash to keep the company running for "well beyond" three years, supporting a phase 3 readout for subcutaneous VK2735, the phase 2 readout for the oral formulation, potentially the monthly subcutaneous dosing trials and initial results for a phase 1b trial of VK0214 in X-ALD. “We're capitalized to proceed with all of these programs,” Lian said. “Fortunately with the obesity program, we will be moving aggressively into a phase 3 development program as soon as possible. With the [MASH] program, the plan there is to have an end-to-phase 2 meeting and receive the feedback and understand what the current thinking is, around registration paths.” Lian said Viking would prefer to partner the MASH program for registrational tests. When asked about the potential for other discovery programs that might be coming down the pike, Lian hinted to some in the works but said Viking would not comment until they are ready for prime time. “We're pretty busy and everybody's stretched pretty thin,” Lian said.