The FDA has approved a pill version of Novo Nordisk’s blockbuster drug Wegovy, giving the company the lead in the pharmaceutical industry pursuit of oral weight loss drugs while also providing patients an easier dosing option compared to the injections that have shaped the fast-growing obesity medication market to date.
In addition to authorizing the Wegovy pill drug for reducing excess body weight, the regulatory decision announced late Monday covers weight maintenance over the long term, so patients who start on once-weekly injectable Wegovy can switch to the oral formulation once they’ve reached maintenance dosing. That also means those who can’t tolerate the higher dose required of the tablet may switch back to lower-dose Wegovy injections. Furthermore, the FDA approval extends to use of the new once-daily tablet for reducing the risk of major cardiovascular events, such as heart attack and stroke.
The placebo-controlled Phase 3 program for oral Wegovy enrolled about 1,300 adults with obesity or overweight along with one or more comorbidities. The FDA approval is based on data from a Phase 3b study that evaluated the 25 mg dose, the lower of the two doses evaluated in the broader program. Results show participants in the study drug arm achieved an average 13.6% loss in body weight measured at week 64 versus an average of 2.2% in the placebo group. Gastrointestinal side effects are common for injectable GLP-1 drugs, and oral semaglutide was no different. But the discontinuation rates across arms in the oral study were similar: 6.9% for the study drug and 5.9% for the placebo.
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The prescribing information for oral Wegovy calls for a 1.5 mg starting dose for four weeks, followed by dose increases that reach a 25 mg maintenance dose at week 17. Under an agreement announced last month between obesity drugmakers and the White House, the starting dose of oral GLP-1 drugs will be priced at $150 per month through TrumpRx, a new website slated to launch in January that will connect patients to low-cost branded medications.
Like injectable Wegovy, the active pharmaceutical ingredient in the Wegovy pill is semaglutide, a peptide engineered to activate the GLP-1 receptor. Peptides aren’t easily absorbed in the stomach, so the new Novo Nordisk pill includes salcaprozate sodium (SNAC), an inactive pharmaceutical ingredient that facilitates stomach absorption of peptides. This approach already has regulatory and commercial validation. SNAC is a key component of Rybelsus, the Novo Nordisk GLP-1 pill approved for type 2 diabetes.
In order for SNAC to work, a patient must take a SNAC-containing drug on an empty stomach in the morning with up to 4 ounces of water — only water, no other fluids. Patients must then wait 30 minutes before eating or drinking anything else or taking any other medications. Oral Wegovy also requires a higher dose. While 25 mg is the maintenance dose for the pill, the highest available dose of injectable Wegovy is 2.4 mg.
The fasting and fluid requirements for oral Wegovy may be off-putting for those who want to start their day with breakfast, or at least morning coffee. The new Novo Nordisk drug could also be challenging for those who need to keep straight the dosing requirements of multiple medications — a large group of patients considering that obesity often overlaps with other medical conditions. That leaves an opening for other oral obesity drugs.
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Eli Lilly’s orforglipron and Structure Therapeutics’ alenglipron are both small molecule agonists of GLP-1 receptors. Earlier this month, Pfizer added an oral GLP-1 drug to its pipeline by licensing a small molecule developed by China-based YaoPharma. Small molecule drugs typically don’t come with the same restrictive dosing regimen as oral peptides.
Last week, Lilly said it had submitted a new drug application for orforglipron as a treatment for obesity. This once-daily pill will have a speedy regulatory review. Last month, the FDA announced orforglipron was one of the drugs selected for a Commissioner’s National Priority Review Voucher, a pilot program that cuts the standard 10 to 12 month review time down to one or two months. These vouchers may be awarded to drugs addressing a national interest or unmet public health need. Wegovy was also awarded one of these vouchers.
Novo Nordisk said it expects an early January U.S. launch for oral Wegovy. This drug is also currently under review by the European Medicines Agency and other regulatory authorities.
“With today’s approval of the Wegovy pill, patients will have a convenient, once-daily pill that can help them lose as much weight as the original Wegovy injection,” Novo Nordisk President and CEO Mike Doustdar said in a prepared statement. “As the first oral GLP-1 treatment for people living with overweight or obesity, the Wegovy pill provides patients with a new, convenient treatment option that can help patients start or continue their weight loss journey.”
Photo by Novo Nordisk