Pfizer to discontinue twice-daily model of weight reduction capsule

Pfizer on Friday stated it will cease creating the twice-daily model of its experimental weight reduction capsule after overweight sufferers taking the drug misplaced vital weight however had bother tolerating the drug in a mid-stage medical research. 

The drugmaker noticed excessive charges of antagonistic unintended effects, which had been principally delicate and gastrointestinal, amongst sufferers. A big share of sufferers additionally stopped taking the drug.

“Presently, twice-daily danuglipron formulation won’t advance into Section 3 research,” the corporate stated.

However Pfizer stated it nonetheless plans to launch section two trial information 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 information earlier than deciding whether or not to begin a section three research on the once-daily capsule, which Wall Avenue views because the extra aggressive type of the therapy.

Shares of Pfizer fell 4% in premarket buying and selling Friday after it introduced the trial outcomes.

Nonetheless, 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 stated might develop to $90 billion. The corporate is betting on a profitable weight reduction capsule to assist it rebound from plummeting demand for its Covid merchandise and a roughly 40% share worth drop this 12 months. 

However buyers have been pessimistic about Pfizer’s potential within the weight reduction drug area because the firm scrapped a special once-daily capsule in June and proceeded with the much less engaging danuglipron. Now, Friday’s information 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 capsule variations of their blockbuster weight reduction and diabetes injections. 

Pfizer’s section two trial on its twice-daily capsule 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 capsule works by mimicking a hormone produced within the intestine referred to as GLP-1, which indicators to the mind when an individual is full.

Pfizer stated the trial on danuglipron met the first aim of demonstrating “statistically vital” reductions in physique weight.

Sufferers who took the capsule twice a day misplaced 6.9% to 11.7% of their physique weight 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 achieve noticed in sufferers who took the placebo, Pfizer’s twice-daily capsule triggered 8% to 13% weight reduction on common at 32 weeks and 5% to 9.5% at 26 weeks.

The corporate stated excessive charges of antagonistic occasions had been noticed amongst sufferers within the research, 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 capsule, in comparison with roughly 40% amongst these on the placebo, in response to Pfizer.

No new questions of safety had been noticed, and danuglipron was not related to elevated liver enzymes like Pfizer’s different discontinued weight reduction capsule.

Knowledge from the section two trial can be offered at a future scientific convention or revealed in a peer-reviewed journal.

The tolerability points align with some analysts’ predictions forward of the info launch. 

Leerink Companions analyst David Risinger wrote in a Monday observe that the proportion of sufferers who discontinue therapy with Pfizer’s twice-daily danuglipron within the section two trial would seemingly be increased than those that stopped taking a once-daily capsule from Eli Lilly.

By comparability, 10% to 21% of sufferers who took Eli Lilly’s capsule, orforglipron, in a mid-stage trial discontinued the therapy at 32 weeks as a consequence of antagonistic unintended effects, he famous.

Risinger stated that is seemingly as a result of danuglipron’s whole day by day dose is way increased, which can trigger extra antagonistic results. Sufferers on the very best dose dimension of Pfizer’s capsule took 400 milligrams every day, whereas these on the very best dosage of Eli Lilly’s drug took 45 milligrams a day.

Pfizer’s phase-two trial additionally did not enable downtitration, or reducing the dose of a drug over time as soon as a selected response has been achieved. Eli Lilly’s mid-stage trial on its capsule did. 

There may be 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 response to some analysts.

They pointed to Pfizer’s second-quarter earnings name, when the corporate’s chief scientific officer, Mikael Dolsten, urged {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 can be unclear till the mid-stage trial information is launched subsequent 12 months.

Notably, the burden loss attributable to twice-daily danuglipron appeared to fall in need of analysts’ expectations. 

Forward of the info launch, a number of analysts stated Pfizer’s twice-daily capsule must be about as efficient as Eli Lilly’s once-a-day capsule to be aggressive. Meaning at the least a 14% to fifteen% weight reduction, Cantor Fitzgerald analyst Louise Chen instructed 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 capsule. 

Overweight or chubby sufferers who took 45 milligrams of Eli Lilly’s capsule as soon as a day misplaced as much as 14.7% of their physique weight, or 34 kilos, after 36 weeks, in response to the corporate’s phase-two trial outcomes.

Eli Lilly’s outcomes seem per the burden discount attributable to a high-dose oral model of Novo Nordisk’s semaglutide – the lively ingredient used within the diabetes drug Ozempic and weight reduction therapy Wegovy – however came visiting a shorter trial interval.

Greater than 2 in 5 adults have weight problems, in response to 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 information was adjusted to incorporate outcomes from the placebo group.