Novo Nordisk’s Alzheimer’s Trials Were a Long Shot. Their Failure Is Still Hitting the Stock.

GLP-1s improved Alzheimer’s-related biomarkers, but didn’t delay disease progression. (AFP via Getty Images)

Key Points

• Novo Nordisk stock falls sharply after GLP-1s fail to slow Alzheimer’s disease progression in clinical trials.
• Semaglutide improved Alzheimer’s-related biomarkers but didn’t delay disease progression.
• Novo Nordisk says it will discontinue the one-year extension period for the trials.

A glimmer of hope for Alzheimer’s patients vanished Monday, when Novo Nordisk said a trial of an oral version of its weight loss drug Wegovy didn’t slow the progression of the disease in two large, late-stage trials.

Novo offered few details, but the trials appear to put an end to hopes that the new GLP-1 drugs will offer a solution for the millions of patients now suffering from Alzheimer’s disease. The company said that some biological measures improved in patients who had received the drug, but that there was no slowing of the progression of the disease. It didn’t indicate any subsets of patients in which the drug worked.

It is far from the first failure of a once-promising Alzheimer’s treatment. The dumpsters behind the big pharma R&D labs are full of Alzheimer’s drugs that didn’t make it through late-stage trials. Even those drugs that seem to have worked, such as the newly approved Kinsula from Eli Lilly and Leqembi from Eisai and Biogen, are far from ideal.

But this latest failure burns more than most. The GLP-1 drugs from Novo Nordisk and Eli Lilly have won a reputation as all but miraculous for their extraordinary efficacy at driving weight loss. Although the scientific rationale was hazy, there was some hope that the GLP-1 drugs might also work to slow the progression of Alzheimer’s.

There are 7.2 million people in America aged 65 and older with Alzheimer’s dementia, according to an estimate from the Alzheimer’s Association. The options for them are very limited.

On Monday, Novo’s American depositary receipt dropped 7%. That is a surprisingly steep selloff because investors weren’t expecting a standout result from the two Novo trials, called evoke and evoke+.

“Although we’re encouraged, we remain cautious,” Citi Research analyst Geoff Meacham wrote last month.

Shares of Biogen, which sells an approved Alzheimer’s drug, were up 4.7%. Shares of Eli Lilly, which sells an approved Alzheimer’s drug and a weight-loss drug that competes with Wegovy, were up 0.7%. The S&P 500 was up 1%.

The two Novo Phase 3 studies involved 3,808 adults. Patients received either a placebo or Rybelsus, a Novo pill approved to treat type 2 diabetes. It is an oral version of Novo’s Ozempic and Wegovy GLP-1 injections. The company is planning to launch a higher-dose pill version as a weight-loss treatment.

“The evoke and evoke+ trials did not confirm superiority of semaglutide versus placebo in the reduction of progression of Alzheimer’s disease,” Novo said in a statement. “While treatment with semaglutide resulted in improvement of Alzheimer’s disease-related biomarkers in both trials, this did not translate into a delay of disease progression.”

Novo said it would cancel a one-year extension period that had been planned for both trials.

There was some excitement among Alzheimer’s experts about the hint from Novo regarding improvement in disease-related biomarkers. “This may suggest a path forward for semaglutide as part of a combination therapy approach,” said the Alzheimer’s Drug Discovery Foundation’s chief scientific officer, Howard Fillit, in a news release.

Novo will present data on the results of the trials at a scientific conference next month.

Write to Josh Nathan-Kazis at josh.nathan-kazis@barrons.com and Nate Wolf at nate.wolf@barrons.com