Pfizer on Friday he said he would stop growing the twice-daily version of the experimental diet pill, after obese patients who received the drug lost significant weight, but had difficulty tolerating the drug in the middle stage clinical study.
The pharmacist observed high rates of adverse side effects, which were mostly mild and gastrointestinal, among patients. A significant share of patients as well stopped taking the pill, which aims to be a more convenient alternative to the wildly popular weight-loss injections.
“At this time, the twice-daily danuglipron formulation will not advance to Phase 3 studies,” the company said.
But Pfizer said it still plans to publish data on a once-daily version of the drug in the first half of 2024, which will “inform a path forward.” The pharmaceutical giant will wait to see those data before deciding whether to start a phase three study of the once-daily pill, which Wall Street sees as the most competitive form of treatment.
Pfizer shares closed 5% lower on Friday after the trial results were announced.
However, the data for the twice-daily drug is a blow to Pfizer’s hopes of winning one 10 billion dollars part of the booming weight-loss drug market, which CEO Albert Burla said could grow 90 billion dollars. The company is betting on a successful diet pill to help it recover from a precipitous drop in demand for its products due to Covid and a share price that has fallen by about 40% this year.
But investors have been pessimistic about Pfizer’s potential in the weight-loss drug space since the company pulled a different once-daily pill in June and switched to the less attractive danuglipron. Now, Friday’s data puts Pfizer even further behind the dominant players in the weight-loss drug market, Eli Lilly and Novo Nordiskwho are struggling to develop pill versions of their blockbuster weight loss and diabetes injections.
by Pfizer phase two test with its twice-daily pill followed about 600 obese adults who did not have type 2 diabetes. The trial looked at the drug’s effect on weight loss after 26 or 32 weeks, at different doses ranging from 40 milligrams to 200 milligrams.
Like Novo Nordisk’s Wegovy and Ozempic, Pfizer’s pill works by mimicking a hormone produced in the gut called GLP-1, which signals the brain when a person is full.
Pfizer said the trial for danuglipron met its primary goal of demonstrating a “statistically significant” reduction in body weight.
Patients taking the twice-daily pill lost 6.9% to 11.7% of their body weight on average at 32 weeks and 4.8% to 9.4% at 26 weeks.
Meanwhile, placebo patients gained 1.4% of their body weight at 32 weeks and 0.17% at 26 weeks.
When adjusting for the difference between the weight gain seen in patients who received placebo, Pfizer’s twice-daily pill caused an average weight loss of 8% to 13% at 32 weeks and 5% to 9.5% at 26 weeks.
The company said high rates of side effects were seen among patients in the study, with up to 73% nausea, up to 47% vomiting and up to 25% diarrhea. More than 50% of patients at all dose sizes stopped taking the pill, compared with about 40% among those who received a placebo, according to Pfizer.
No new safety issues were seen, and danuglipron was not associated with elevated liver enzymes like Pfizer’s other discontinued weight loss pill.
Data from the second phase of the trial will be presented at a future scientific conference or published in a peer-reviewed journal.
The tolerance issues are in line with some analysts’ forecasts ahead of the data release.
Leerink Partners analyst David Risinger wrote in a note Monday that the proportion of patients stopping Pfizer’s twice-daily danuglipron in the phase two trial will likely be higher than those who stopped taking a once-a-day pill. day from Eli Lilly.
By comparison, 10% to 21% of patients who received the Eli Lilly pill, orforglipron, in mid-stage test stopped treatment at 32 weeks because of adverse side effects, he noted.
Risinger said this is likely because the total daily dose of danuglipron is much higher, which may cause more side effects. Patients taking the highest dose of the Pfizer pill took 400 milligrams each day, while those taking the highest dose of the Eli Lilly drug took 45 milligrams a day.
Pfizer’s phase two trial also did not allow for down-titration or lowering the dose of a drug over time once a certain response was achieved. Eli Lilly’s mid-stage trial for its pill did.
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It is hoped that patients will tolerate the once-daily version of danuglipron better than the twice-daily form. Pfizer appears to believe that a daily version of the drug could reduce gastrointestinal side effects, according to some analysts.
They pointed to Pfizer’s second-quarter earnings call, when the company’s chief scientific officer, Mikael Dolsten, suggested that a once-daily version may improve patient tolerability of the drug, which could reduce the gastrointestinal side effects “that have been considered limiting” of danuglipron.
But Barclays analyst Carter Gould wrote in a note on Friday that he remained skeptical that a daily release would “move the needle on tolerance given the starting point of this debate.”
He added that “it is increasingly apparent that the company will have to look for external assets to bring to market the opportunity it has presented.”
Notably, the weight loss induced by twice-daily danuglipron appeared to fall short of some analysts’ expectations.
Wall Street was looking for the pill to show a 14% to 15% weight loss to be competitive, Cantor Fitzgerald analyst Louise Chen wrote in a note on Friday. Doctors think a 15 percent weight loss is “good enough” to convince them to switch from prescribing injectable weight-loss drugs to oral versions, Chen said.
Leerink’s Risinger also wrote in October that Pfizer’s danuglipron needs to show weight loss at “mid-adolescent” rates to be considered competitive with Eli Lilly’s once-daily pill in particular.
Obese or overweight patients taking 45 milligrams of Eli Lilly’s pill once a day lost up to 14.7% of their body weightor 34 pounds, after 36 weeks, according to the company’s Phase II trial results.
Eli Lilly’s results appeared to be in line with the weight reduction caused by a high-dose oral version of Novo Nordisk’s semaglutide – the active ingredient used in diabetes drug Ozempic and weight loss treatment Wegovy – but came in a smaller trial period.
Both pills from Eli Lilly and Novo Nordisk appear to be “superior to danuglipron at this stage,” TD Cowen analyst Steve Scala said in a note on Friday.
“Overall, this is a worse-than-expected result for a program that was already playing catch-up,” Scala said of the Pfizer pill data.
More than 2 in 5 adults are obese, according to the National Institutes of Health. About 1 in 11 adults are severely obese.
Clarification: This story has been updated to reflect that some weight loss data were adjusted to include results from the placebo group.