Novo Nordisk Seeks Oral Semaglutide Approval, CV Indications on New Drug and Injectable

Novo Nordisk today filed for FDA approval of oral semaglutide, which would be the first glucagon-like peptide-1 (GLP-1) receptor agonist in a pill form. The drug maker also filed for a new cardiovascular (CV) indication for its once-a-week injectable form of semaglutide, which the FDA approved in December 2017. The weekly injectable GLP-1 receptor agonist is sold as Ozempic. The company announced the filings in a statement.

For oral semaglutide, the drug maker submitted 2 New Drug Applications (NDAs): the first seeks approval to control blood glucose to treat type 2 diabetes (T2D) through a priority review process that would take 6 months. A second NDA was filed seeking an indication to reduce major adverse CV events, such as heart attacks, strokes, and CV death, in adults with T2D and established CV disease; that review is expected to take 10 months.

The filings are based on the PIONEER clinical trial program for oral semaglutide, which included a cardiovascular outcomes trial (CVOT), and SUSTAIN 6, a CVOT for the once-weekly injectable semaglutide. Unlike the injectable form, the oral form of semaglutide would be taken once a day.

"We are very excited about these three regulatory filings with the FDA as they represent a significant milestone for the company, but most importantly represent new potential treatment options for adults living with type 2 diabetes," Todd Hobbs, MD, vice president and US chief medical officer of Novo Nordisk, said in the company’s statement. "We know that many adults with type 2 diabetes are still struggling to control their blood sugar and are at increased cardiovascular risk. We hope that, if approved, these products can help those patients."

Novo Nordisk’s filings come as both the American College of Cardiology (ACC) and the American Diabetes Association have endorsed the use of GLP-1 receptor agonist class in clinical guidelines for patients with T2D and atherosclerotic CV disease. During last weekend’s ACC's 68th Annual Scientific Session in New Orleans, Louisiana, the ACC and the American Heart Association went a step further and said GLP-1 receptor agonists and sodium glucose co-transporter 2 (SGLT2) inhibitors may be used in primary prevention, following results from CVOTs that suggest these classes can prevent long-term complications from heart failure.

Oral semaglutide could address an unmet need in patients with T2D and CV risk who are overweight, as the GLP-1 receptor agonist class has been shown to help patients achieve significant weight loss. However, not all patients are willing to use an injectable drug, even one only needed once a week.

An ACC panel discussion reviewed case studies on when to prescribe GLP-1 receptor agonists or SGLT2 inhibitors, and cardiologists said there are cases in which GLP-1 receptor agonists are indicated, but patients will not take an injectable drug. In one scenario described during the ACC session, an obese female patient was prescribed an SGLT2 inhibitor instead, but the physician commented that while this would control her blood sugar, it would not provide the same weight loss benefits.

Hobbs told The American Journal of Managed Care^® in an interview that oral semaglutide was developed with these patients in mind. “One of the reasons we for many years have tried to develop an oral GLP-1 is because the injection is still a barrier,” he said. “With patients, that’s significant, but it’s also significant with many primary care providers. Our hope and expectation is that we will be able to see more individuals benefit from GLP-1s in diabetes, and also in primary care in particular.”

Asked to comment on the importance of the endorsements of the GLP-1 receptor agonist class in recent guidelines updates, Hobbs said, “The impact of the guidelines is important, no matter the outcome of the regulatory decision is around the labeling round CV improvement.”

He noted that the recent ACC Expert Consensus Decision Pathway singled out Novo Nordisk’s liraglutide (Victoza) among the GLP-1 receptor agonist class. This injectable T2D therapy is taken once a day and has previously received an indication to reduce the risk of CV death.