Pfizer on Friday said it could stop developing the twice-daily version of its experimental weight reduction pill after obese patients taking the drug lost significant weight but had trouble tolerating the drug in a mid-stage clinical study.
The drugmaker observed high rates of adversarial unwanted effects, which were mostly mild and gastrointestinal, amongst patients. A big share of patients also stopped taking the drug.
“Right now, twice-daily danuglipron formulation won’t advance into Phase 3 studies,” the corporate said.
But Pfizer said it still plans to release phase two trial data on a once-a-day version of the drug in the primary half of 2024, which is able to “inform a path forward.” The pharmaceutical giant will wait to see that data before deciding whether to begin a phase three study on the once-daily pill, which Wall Street views because the more competitive type of the treatment.
Shares of Pfizer fell 4% in premarket trading Friday after it announced the trial results.
Still, the info on the twice-daily drug is a blow to Pfizer’s hopes to win a $10 billion slice of the booming weight reduction drug market, which CEO Albert Bourla has said could grow to $90 billion. The corporate is betting on a successful weight reduction pill to assist it rebound from plummeting demand for its Covid products and a roughly 40% share price drop this yr.
But investors have been pessimistic about Pfizer’s potential in the burden loss drug space because the company scrapped a special once-daily pill in June and proceeded with the less attractive danuglipron. Now, Friday’s data puts Pfizer even further behind the dominant players in the burden loss drug market, Eli Lilly and Novo Nordisk, that are racing to develop more convenient pill versions of their blockbuster weight reduction and diabetes injections.
Pfizer’s phase two trial on its twice-daily pill followed around 600 obese adults who didn’t have Type 2 diabetes. The trial examined the drug’s effect on weight reduction after 26 or 32 weeks, at different dosage amounts starting from 40 milligrams to 200 milligrams.
Like Novo Nordisk’s Wegovy and Ozempic, Pfizer’s pill works by mimicking a hormone produced within the gut called GLP-1, which signals to the brain when an individual is full.
Pfizer said the trial on danuglipron met the first goal of demonstrating “statistically significant” reductions in body weight.
Patients who took the pill twice a day lost 6.9% to 11.7% of their body weight on average at 32 weeks, and from 4.8% to 9.4% at 26 weeks.
Meanwhile, patients on a placebo gained 1.4% of their body weight at 32 weeks and 0.17% at 26 weeks.
When adjusting for the difference between the burden gain observed in patients who took the placebo, Pfizer’s twice-daily pill caused 8% to 13% weight reduction on average at 32 weeks and 5% to 9.5% at 26 weeks.
The corporate said high rates of adversarial events were observed amongst patients within the study, with as much as 73% experiencing nausea, as much as 47% vomiting and as much as 25% experiencing diarrhea. Greater than 50% of patients across all dose sizes stopped taking the pill, in comparison with roughly 40% amongst those on the placebo, in response to Pfizer.
No latest issues of safety were observed, and danuglipron was not related to increased liver enzymes like Pfizer’s other discontinued weight reduction pill.
Data from the phase two trial shall be presented at a future scientific conference or published in a peer-reviewed journal.
Wall Street’s expectations
The tolerability issues align with some analysts’ predictions ahead of the info release.
Leerink Partners analyst David Risinger wrote in a Monday note that the proportion of patients who discontinue treatment with Pfizer’s twice-daily danuglipron within the phase two trial would likely be higher than those that stopped taking a once-daily pill from Eli Lilly.
By comparison, 10% to 21% of patients who took Eli Lilly’s pill, orforglipron, in a mid-stage trial discontinued the treatment at 32 weeks as a consequence of adversarial unwanted effects, he noted.
Risinger said that is likely because danuglipron’s total each day dose is way higher, which can cause more adversarial effects. Patients on the very best dose size of Pfizer’s pill took 400 milligrams every day, while those on the very best dosage of Eli Lilly’s drug took 45 milligrams a day.
Pfizer’s phase-two trial also didn’t allow downtitration, or decreasing the dose of a drug over time once a particular response has been achieved. Eli Lilly’s mid-stage trial on its pill did.
There’s hope that patients will higher tolerate the once-daily version of danuglipron in comparison with the twice-daily form. Pfizer appears to imagine a once-daily version of the drug could lessen gastrointestinal unwanted effects, in response to some analysts.
They pointed to Pfizer’s second-quarter earnings call, when the corporate’s chief scientific officer, Mikael Dolsten, suggested that a once-daily version may improve a patient’s tolerability of the drug, which could lessen the gastrointestinal unwanted effects “which have been seen as limiting” danuglipron.
But the consequences shall be unclear until the mid-stage trial data is released next yr.
Notably, the burden loss brought on by twice-daily danuglipron appeared to fall in need of analysts’ expectations.
Ahead of the info release, several analysts said Pfizer’s twice-daily pill needs to be about as effective as Eli Lilly’s once-a-day pill to be competitive. Meaning at the very least a 14% to fifteen% weight reduction, Cantor Fitzgerald analyst Louise Chen told CNBC earlier this month.
Risinger also wrote in October that Pfizer’s danuglipron needs to point out weight reduction within the “mid-teens” percentages to be considered competitive with Eli Lilly’s pill.
Obese or chubby patients who took 45 milligrams of Eli Lilly’s pill once a day lost as much as 14.7% of their body weight, or 34 kilos, after 36 weeks, in response to the corporate’s phase-two trial results.
Eli Lilly’s results appear consistent with the burden reduction brought on by a high-dose oral version of Novo Nordisk’s semaglutide – the lively ingredient utilized in the diabetes drug Ozempic and weight reduction treatment Wegovy – but got here over a shorter trial period.
Greater than 2 in 5 adults have obesity, in response to the National Institutes of Health. About 1 in 11 adults have severe obesity.
Clarification: This story was updated to reflect that some weight-loss data was adjusted to incorporate results from the placebo group.