Pfizer on Friday mentioned it might cease creating the twice-daily model of its experimental weight reduction tablet after overweight sufferers taking the drug misplaced weight however had hassle tolerating the drug in a mid-stage scientific examine.
The drugmaker noticed excessive charges of hostile unintended effects, which have been principally gentle and gastrointestinal, amongst sufferers. A big share of sufferers additionally stopped taking the drug.
“At the moment, twice-daily danuglipron formulation won’t advance into Section 3 research,” the corporate mentioned.
However Pfizer mentioned it nonetheless plans to launch section two trial knowledge on a once-a-day model of the drug within the first half of 2024, which is able to “inform a path ahead.” The pharmaceutical large will wait to see that knowledge earlier than deciding whether or not to start out a section three examine on the once-daily tablet, which Wall Avenue views because the extra aggressive type of the remedy.
Shares of Pfizer fell 4% in premarket buying and selling Friday after it introduced the trial outcomes.
Nonetheless, the information 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 mentioned might develop to $90 billion. The corporate is betting on a profitable weight reduction tablet to assist it rebound from plummeting demand for its Covid merchandise and a roughly 40% share value drop this yr.
However buyers have been pessimistic about Pfizer’s potential within the weight reduction drug house because the firm scrapped a special once-daily tablet in June and proceeded with the much less enticing danuglipron. Now, Friday’s knowledge places Pfizer even additional behind the dominant gamers within the weight reduction drug market, Eli Lilly and Novo Nordisk, that are racing to develop extra handy tablet variations of their blockbuster weight reduction and diabetes injections.
Pfizer’s section two trial on its twice-daily tablet adopted round 600 overweight adults who didn’t have Sort 2 diabetes. The trial examined the drug’s impact on weight reduction after 26 or 32 weeks, at totally different dosage quantities starting from 40 milligrams to 200 milligrams.
Like Novo Nordisk’s Wegovy and Ozempic, Pfizer’s tablet works by mimicking a hormone produced within the intestine known as GLP-1, which indicators to the mind when an individual is full.
All dose sizes of Pfizer’s tablet confirmed “statistically important reductions” in physique weight starting from 6.9% to 11.7% on common at 32 weeks, and from 4.8% to 9.4% at 26 weeks.
In the meantime, sufferers on a placebo gained 1.4% of their physique weight at 32 weeks and 0.17% at 26 weeks. When adjusting for the distinction between the burden acquire noticed in sufferers who took the placebo, Pfizer’s twice-daily tablet prompted 8% to 13% weight reduction on common at 32 weeks and 5% to 9.5% at 26 weeks.
The corporate mentioned excessive charges of hostile occasions have been noticed amongst sufferers within the examine, with as much as 73% experiencing nausea, as much as 47% vomiting and as much as 25% experiencing diarrhea. Greater than 50% of sufferers throughout all dose sizes stopped taking the tablet, in comparison with roughly 40% amongst these on the placebo, in accordance with Pfizer.
No new questions of safety have been noticed, and danuglipron was not related to elevated liver enzymes like Pfizer’s different discontinued weight reduction tablet.
Information from the section two trial will probably be offered at a future scientific convention or revealed in a peer-reviewed journal.
Wall Avenue’s expectations
The tolerability points align with some analysts’ predictions forward of the information launch.
Leerink Companions analyst David Risinger wrote in a Monday word that the proportion of sufferers who discontinue remedy with Pfizer’s twice-daily danuglipron within the section two trial would probably be larger than those that stopped taking a once-daily tablet from Eli Lilly.
By comparability, 10% to 21% of sufferers who took Eli Lilly’s tablet, orforglipron, in a mid-stage trial discontinued the remedy at 32 weeks attributable to hostile unintended effects, he famous.
Risinger mentioned that is probably as a result of danuglipron’s whole day by day dose is much larger, which can trigger extra hostile results. Sufferers on the best dose dimension of Pfizer’s tablet took 400 milligrams every day, whereas these on the best dosage of Eli Lilly’s drug took 45 milligrams a day.
Pfizer’s phase-two trial additionally did not enable downtitration, or lowering the dose of a drug over time as soon as a selected response has been achieved. Eli Lilly’s mid-stage trial on its tablet did.
There’s hope that sufferers will higher tolerate the once-daily model of danuglipron in comparison with the twice-daily kind. Pfizer seems to imagine a once-daily model of the drug might reduce gastrointestinal unintended effects, in accordance with some analysts.
They pointed to Pfizer’s second-quarter earnings name, when the corporate’s chief scientific officer, Mikael Dolsten, steered {that a} once-daily model might enhance a affected person’s tolerability of the drug, which might reduce the gastrointestinal unintended effects “which have been seen as limiting” danuglipron.
However the results will probably be unclear till the mid-stage trial knowledge is launched subsequent yr.
Notably, the burden loss attributable to twice-daily danuglipron appeared to fall in need of analysts’ expectations.
Forward of the information launch, a number of analysts mentioned Pfizer’s twice-daily tablet needs to be about as efficient as Eli Lilly’s once-a-day tablet to be aggressive. Meaning at the least a 14% to fifteen% weight reduction, Cantor Fitzgerald analyst Louise Chen informed CNBC earlier this month.
Risinger additionally wrote in October that Pfizer’s danuglipron wants to indicate weight discount within the “mid-teens” percentages to be thought-about aggressive with Eli Lilly’s tablet.
Overweight or chubby sufferers who took 45 milligrams of Eli Lilly’s tablet as soon as a day misplaced as much as 14.7% of their physique weight, or 34 kilos, after 36 weeks, in accordance with the corporate’s phase-two trial outcomes.
Eli Lilly’s outcomes seem according to the burden discount attributable to a high-dose oral model of Novo Nordisk’s semaglutide – the energetic ingredient used within the diabetes drug Ozempic and weight reduction remedy Wegovy – however came visiting a shorter trial interval.
Greater than 2 in 5 adults have weight problems, in accordance with the Nationwide Institutes of Well being. About 1 in 11 adults have extreme weight problems.
Clarification: This story was up to date to mirror that some weight-loss knowledge was adjusted to incorporate outcomes from the placebo group.
