Our Take: Novo Nordisk eyes potential cardiovascular indication for semaglutide, adds CB1 blocker to weight-loss pipeline
With the release of positive initial study results last week — including a 20% reduction in the risk of major adverse cardiovascular events (MACE), Danish drugmaker Novo Nordisk is poised to experience even greater demand for semaglutide, a GLP-1 analog the company markets as Wegovy for weight loss and Ozempic for diabetes.
The Phase III SELECT trial evaluated a 2.4 mg dose of semaglutide administered subcutaneously once weekly (i.e., the Wegovy maintenance dose) versus placebo in 17,604 adults with cardiovascular disease who were at least 45 years old and had a body mass index of at least 27 kg/m2 — but no history of diabetes. Treatment was given as an adjunct to standard of care to prevent MACE for up to five years.
The primary objective of the study was to show semaglutide’s superiority relative to placebo in reducing the incidence of three-point MACE, which consisted of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
The results demonstrated a statistically significant MACE reduction of 20% in the semaglutide group compared with the placebo group.
“People living with obesity have an increased risk of cardiovascular disease but to date, there are no approved weight management medications proven to deliver effective weight management while also reducing the risk of heart attack, stroke, or cardiovascular death. Therefore, we are very excited about the results from SELECT showing that semaglutide 2.4 mg reduces the risk of cardiovascular events,” said Martin Holst Lange, executive vice president for development at Novo Nordisk. “[The trial] has demonstrated that semaglutide 2.4 mg has the potential to change how obesity is regarded and treated.”
Novo Nordisk noted that semaglutide appeared to have a safe and well-tolerated profile in line with previous clinical trials. Detailed results from the trial are to be presented at a conference later this year.
The company said it anticipates filing for regulatory approval of a Wegovy label indication expansion in 2023.
Novo Nordisk also announced last week that it agreed to acquire Montreal-based Inversago Pharma for as much as $1.075 billion. The company did not specify how much of that total would be paid up front and how much might be paid if predetermined milestones are achieved.
Inversago develops cannabinoid CB1 receptor blocker therapies for treating complications associated with cardiometabolic and fibrotic diseases. The company’s lead candidate, INV-202, has demonstrated “weight loss potential” in early stage clinical testing and is being evaluated as a treatment for diabetic kidney disease in a Phase II trial.
CB1 plays a key role in appetite regulation, according to Novo Nordisk, and the company plans to investigate INV-202 as a possible treatment for obesity and related complications.
“This promising class of medicine pioneered by the Inversago team could lead to life-changing new treatment options for those living with a serious chronic disease and, in particular, may offer alternative or complementary solutions for people living with obesity,” Lange said.
The acquisition is subject to regulatory approval and other customary closing conditions; the companies expect to complete it before the end of the year.
Our Take: Semaglutide is already a blockbuster drug for Novo Nordisk, and the addition of a cardiovascular indication to the Wegovy label could dramatically increase sales — especially if more insurers and Medicare decide to cover the cost of semaglutide.
Currently, some payers only provide coverage for semaglutide as a diabetes treatment, and federal law (from 20 years ago) bans Medicare’s prescription drug benefit from covering weight-loss drugs. Novo Nordisk has been lobbying to persuade lawmakers to eliminate the Medicare ban, and an expanded label with an indication for cardiovascular disease could aid the company’s efforts.
In its earnings report for the first half of 2023, Novo Nordisk said its net sales were up approximately 30%, largely because of increased sales within its diabetes and obesity category of products. Specifically, its GLP-1 diabetes sales increased 50% at constant exchange rates (CER), and its obesity care category, which includes Wegovy and Saxenda (liraglutide), grew 157% percent at CER — to 18.1 billion Danish kroner, or approximately $2.7 billion. Sales of Wegovy accounted for more than $1 billion of that $2.7 billion total, according to Fierce Pharma.
The growth in Wegovy sales has skyrocketed despite constraints on the drug’s supply. In May, Novo Nordisk began limiting the supply of lower, starting doses of Wegovy in the U.S. to “safeguard continuity of care,” until the company can adequately scale up manufacturing. Although it said in May the restrictions were temporary, last week Novo Nordisk said it would continue to ration the lower-dose strengths, possibly into next year.
If the company can position Wegovy as a treatment for cardiovascular conditions, that will almost certainly lead to a substantial increase in prescriptions.
“People will take it more seriously,” Dr. Beverly Tchang, an endocrinologist at Weill Cornell Medicine in New York City, said in an Aug. 10 article about the SELECT trial results published by the journal Nature.
In the same article, Dr. Michael Blaha, director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, said the SELECT trial “is probably the most important study in my field in the last ten years. It gets to that cardiometabolic risk that’s been difficult to treat in practice.”
The article noted that researchers expected Wegovy to protect against heart disease because “obesity itself is an important risk factor for cardiovascular disease,” and weight loss can improve other risk factors, such as blood pressure and cholesterol levels. Additional data could help determine what specifically about Wegovy is producing the cardio-protective effect.
Dr. Blaha believes the SELECT trial likely underestimates the cardiovascular benefits of the drug because the study only examined a limited set of severe cardiovascular events.
Dr. Martha Gulati, director of preventive cardiology at Cedars-Sinai Medical Center in Los Angeles, said in the article that broader insurance coverage “will be a game-changer for the clinical practice of preventive cardiology.”
Sage Therapeutics’ Zurzuvae (zuranolone) is the first oral medication to receive FDA approval for postpartum depression, a condition that affects approximately 500,000 women each year. Zurzuvae is taken once daily for two weeks and, based on trial results, can ease symptoms as soon as the third day. Sage said in a news release it expects to launch the drug in the fourth quarter. The Cambridge, Mass.-based biopharmaceutical firm co-developed zuranolone with Biogen, and the companies had hoped to have the drug approved as a treatment for major depressive disorder (MDD) as well — but the FDA requested additional clinical testing for the MDD indication. Biogen CEO Christopher Viehbacher said the companies would review the FDA’s feedback and determine their next steps. Meanwhile, Sage’s stock dropped more than 50% on news of the rejected indication, and the company is considering trimming its workforce and pipeline.
Insurers will receive at least $12.8 billion in Medicare Advantage bonus payments this year based on their star ratings, a recent KFF analysis indicates, up 28% from 2022. The $2.8 billion increase in payments outpaces the 8% increase in enrollment during the same period. In all, 85% of MA enrollees are in plans that will receive bonus payments this year, up from 75% last year. UnitedHealthcare and Humana, which collectively account for 47% of MA enrollment, are expected to receive 49% of the bonus payments ($3.9 billion for UnitedHealthcare and $2.3 billion for Humana). With 99% of its plans earning bonuses, Kaiser Permanente is set to receive the highest average bonus payment per enrollee, at $523.
The Supreme Court temporarily blocked Purdue Pharma’s bankruptcy settlement agreement on Thursday and said it would hear arguments before year-end. A provision of the agreement shields members of the Sackler family, who still technically own Purdue, from future civil lawsuits pertaining to Oxycontin’s role in the opioid epidemic. The agreement calls for the Sacklers to give up ownership of Purdue and contribute up to $6 billion in cash, some of which is to be distributed to hard-hit communities and victims of the opioid crisis. Purdue would be renamed and its profits would be used toward efforts to prevent and treat addiction. A federal judge rejected the settlement in December 2021 on the grounds that the bankruptcy judge did not have the authority to approve the agreement protecting the Sacklers, when they had not filed for personal bankruptcy protection. An appeals court overruled the lower court’s decision in May, allowing the plan to proceed. That move prompted the U.S. Bankruptcy Trustee to file the application with the Supreme Court for the stay.
Vanderbilt University Medical Center is being investigated by the Department of Health and Human Services for possible civil rights violations in connection with the health system’s release of patients’ medical information to Tennessee’s attorney general. The AG’s office said it requested patient records from VUMC’s clinic that provides transgender care as part of a probe into possible medical billing fraud, The Associated Press reported. Attorneys for two of the patients recently filed a class-action lawsuit against VUMC, claiming the health system violated their privacy by releasing their personal information without adequately de-identifying it.
Miami-based Cano Health is seeking a buyer after reporting a net loss of $270.7 million for the second quarter (vs. a loss of $14.6 million in the same quarter of 2022) and acknowledging “substantial doubt about [its] ability to continue as a going concern within one year.” The value-based primary care chain attributed the results partly to a higher medical cost ratio (103.5% vs. 82.6% in the previous year’s second quarter), driven largely by a reduction in Medicare risk adjustment revenue, and higher third-party medical costs due to increased utilization. The company expects to lay off approximately 700 employees, or 17% of its workforce, in the third quarter and plans to cease operations in California, New Mexico, and Illinois by this fall, with an exit from Puerto Rico to follow by January. Cano Health’s stock closed at $1.52 per share on Thursday, just before the earnings report was released, and traded as low as $0.39 on Friday.
The federal government is investing $100 million to address the critical need for more nurses, HHS said in a news release. The Health Resources and Services Administration will award the funding to organizations through programs that train licensed practical and vocational nurses to become registered nurses; train nurses to deliver primary care, mental health care, and maternal health care; and support more faculty at nursing schools. HHS provided a link to the full list of awards.
The Social Determinants of Health — Moving Beyond Screen-and-Refer to Intervention. NEJM, 8.10.23 (registration required)
What Will AI Do for Health Care? BCG Perspectives, (Boston Consulting Group, n.d.)
Food Is Medicine Movement—Key Actions Inside and Outside the Government. JAMA Health Forum, 8.10.23