Pfizer Discontinues Twice-Daily Obesity Pill After Study Shows High Side-Effect Rates

Pfizer said it won’t put the twice-daily version of its experimental weight-loss pill, called danuglipron, into further testing.
Pfizer Discontinues Twice-Daily Obesity Pill After Study Shows High Side-Effect Rates
A person walks past a Pfizer logo in New York City on April 1, 2021. (Carlo Allegri/Reuters)
Bill Pan

Pfizer on Dec. 1 said it will halt the development of its twice-daily version of its experimental weight-loss pill after participants in a midstage clinical study showed high rates of having trouble tolerating the drug.

Pfizer’s drug, called danuglipron, is a GLP-1 receptor agonist that works the same way as weight-loss injections from Novo Nordisk and Eli Lilly, mimicking a hormone that controls feelings of satiety and how fast the contents of the stomach reach the gut. Unlike those drugs, danuglipron comes as an oral tablet, an advantage in convenience that Pfizer hoped could give it a competitive edge in a race to carve up the multibillion-dollar market.

In a report released on Dec. 1, however, Pfizer said it will stop developing the twice-daily version of danuglipron, citing high rates of gastrointestinal side effects and participant dropout in the phase-2 study.

According to the data, the drug did lead to significant results during the randomized, double-blind, placebo-controlled study, with placebo-adjusted body weight reductions within the range of 8 to 13 percent at 32 weeks and 5 to 9.5 percent at 26 weeks.

However, the study’s participants reported experiencing high rates of gastrointestinal side effects, including nausea (up to 73 percent), vomiting (up to 47 percent), and diarrhea (up to 25 percent). The side effects were generally mild, Pfizer said.

On top of that, more than half of the participants across all dose sizes stopped taking the pill, compared with about 40 percent of those who were given the placebo.

Pfizer added that it didn’t see any new safety issues and that danuglipron wasn’t found to be associated with increased liver enzymes, which was the reason the company discontinued its other experimental weight-loss pill, lotiglipron.

Pfizer said it will focus on improving the once-daily version of danuglipron, which is currently being tested and could be more tolerable than the twice-daily form. The test results are expected in the first half of 2024.

“We believe an improved once-daily formulation of danuglipron could play an important role in the obesity treatment paradigm, and we will focus our efforts on gathering the data to understand its potential profile,” Dr. Mikael Dolsten, Pfizer’s chief science officer, said in a statement.

The news comes as Pfizer is mounting a $3.5 billion “enterprise-wide cost realignment” campaign. Over the past weeks, the pharma giant has announced plans to shut down multiple sites in Michigan and New Jersey, as well as in Ireland, laying off thousands of employees on both sides of the Atlantic.

The latest to be put on the chopping block is Pfizer’s research site in Groton, Connecticut. Although it’s unclear how many jobs will be slashed, more than 2,600 people were employed at the Gordon office as of January 2022.

“Various areas of Pfizer’s global enterprise are making changes to operate more efficiently and effectively,” a Pfizer spokesperson said last week. “Part of the effort will result in some job loss across a number of our locations, including Groton.”

The cost-cutting spree appears to be prompted by the shrinking demand for the company’s COVID-19 vaccine Comirnaty and antiviral Paxlovid.

In the third quarter of 2023, Pfizer reported $5.6 billion in COVID-related inventory write-offs and other charges. This included a $4.2 billion revenue reversal due to the Biden administration’s returning some 7.9 million unused doses of Paxlovid it purchased during the COVID-19 pandemic. Overall, Pfizer recorded third-quarter revenue of $13.23 billion, down 42 percent from the same period a year ago.

“As the federal government transitions away from distributing these products, access will primarily depend on the arrangements in the private commercial market among each of the particular drug manufacturers and private insurers,” Health and Human Services Secretary Xavier Becerra said in an Oct. 27 letter to manufacturers and distributors.