Pharmaceutical giant Pfizer announced Friday that it will discontinue further development of the twice-daily formulation of its experimental obesity drug danuglipron after underwhelming mid-stage trial results showing modest weight loss accompanied by concerning gastrointestinal side effects leading to significant patient dropouts.
Twice-Daily Danuglipron Fails to Impress in Phase 2b Trial
Danuglipron, an oral GLP-1 receptor agonist, was Pfizer’s hope to take on Novo Nordisk’s dominant Wegovy injection in the burgeoning obesity drug market. But in a Phase 2b clinical trial with over 500 obese patients, the twice-daily pill formulation of danuglipron failed to demonstrate substantial weight loss benefits and was plagued by adverse side effects causing many patients to leave the six-month study early.
By the trial’s end, only 60% of patients remained on the highest 9 mg dose of danuglipron compared to 75% still taking the placebo. Across all danuglipron doses, the drug only achieved 5% to 7% greater weight loss than placebo – falling short of the minimum 10% benchmark to be considered clinically meaningful.
| Twice-Daily Danuglipron Phase 2b Trial Results |
|-|-|
| Patients remaining at end of 6 months | 60% on 9 mg dose vs. 75% on placebo |
| Weight loss compared to placebo | 5-7% greater |
| Goal for meaningful weight loss | ≥10% |
The rather lackluster efficacy came with considerable tolerability issues as well, with over 20% of patients on the higher doses reporting gastrointestinal adverse events like nausea, vomiting, and diarrhea.
While the drug did demonstrate statistically significant weight loss and triglyceride reduction, the poor compliance and dropouts evidently gave Pfizer cold feet about advancing the twice-daily formulation of danuglipron.
Pfizer Opts to Forge Ahead with Once-Daily Dosage
Rather than scrapping danuglipron entirely, Pfizer has decided to focus future development on a once-daily dose of the drug. A separate Phase 2 trial evaluating different once-daily danuglipron doses up to 18 mg is still underway.
These initial results announced today only related to the twice-daily pill regimen which required one dose in the morning and a second booster dose at night. The company is betting that a single daily dose could help improve tolerability and make the treatment easier for patients to stick with long-term.
While specifics on the once-daily formulation’s efficacy remain undisclosed for now, Pfizer indicated that the initial profile looks “encouraging” thus far. So rather than invest additional resources to move the twice-daily dose to Phase 3, the pharmaceutical giant is cutting its losses and prioritizing the still promising once-daily version.
$900 Billion Obesity Drug Market at Stake
Danuglipron is Pfizer’s ambitious play to grab a share of the rapidly expanding anti-obesity therapeutic market from current leaders like Novo Nordisk. With obesity affecting nearly 40% percent of American adults, new weight loss medications represent blockbuster revenue opportunities for drug makers.
Strong demand for Wegovy has propelled Novo Nordisk’s sales over $900 billion in the last year alone. But despite its dominance, Wegovy requires cumbersome weekly injections administered with confusing dose escalation protocols. Patients and doctors alike have clamored for more convenient and easily administered oral alternatives.
Pfizer clearly hoped danuglipron could be that coveted pill and carve out a niche against the Danish pharma’s injectable options. While this temporary setback with the twice-daily formulation raises questions, the New York-based company still aims to eventually bring an oral daily GLP-1 tablet to the obesity medication arena.
What’s Next for Pfizer’s Obesity Program?
In reaction to today’s danuglipron update that dashed hopes for quick progress, Pfizer stock dropped over 6% to reach a 2-year low. But obesity still represents a major new frontier for pharmaceutical research, so Pfizer maintains long term plans in this emerging category.
Now analysts will be watching closely for results from the ongoing once-daily trial expected in mid-2024. Strong data could reinvigorate enthusiasm for danuglipron’s potential among doctors, patients, and investors.
However, setbacks with the once-daily dose would likely spell the end of the road for danuglipron after years in development. In that scenario, Pfizer may need to explore acquiring or licensing alternate obesity drug candidates to stay competitive in this exponentially growing market targeted by most major pharmas today.
While the initial danuglipron results leave much to be desired, Pfizer’s commitment to keep advancing the once-daily dose shows they believe this program still holds promise as an oral anti-obesity agent. The company has billions in cash stockpiled post-COVID to fuel new growth drivers amid declining pandemic revenue.
An efficacious danuglipron pill would nicely complement Pfizer’s pipeline while aiding the fight against obesity. For investors however, concerns will linger until the next trial confirms this asset’s commercial viability and potential to gain ground on runaway leader Wegovy.
All eyes now turn to the ongoing once-daily Phase 2 trial. Those results, for better or worse, will determine if danuglipron becomes a new weapon for battling the global obesity epidemic or another failed experiment unable to stack up against the formidable competition.
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