ADA 2023 preview – Lilly’s oral obesity data leave room for Pfizer

Weight loss with Lilly’s oral GLP-1 agonist orforglipron falls short of the previously revealed “mid-teens” benchmark.

Lilly has yet to enter the injectable obesity market with its GIP/GLP-1 agonist Mounjaro, but oral drugs are already the next frontier. New data, which were apparently released accidentally yesterday, gave investors the first look at the group's oral GLP-1 contender orforglipron, which is in phase 3 development.

The company previously talked up orforglipron’s convenience advantage but warned that it is unlikely to be as effective as Mounjaro. Mid-stage data revealed in an American Diabetes Association abstract showed 12.6% weight loss with the oral at 26 weeks – lower than the 14-15% Lilly had previously estimated. At the same time point, Mounjaro had produced weight loss of around 15%.

Evercore ISI’s Umer Raffat noted that this 14-15% weight loss estimate had come at 36 weeks, so perhaps the figure will improve over time. However, he also highlighted an apparently plateauing dose response with orforglipron in the abstract, which is no longer available on the ADA website – the meeting is set to start on Friday.

Weight loss with Lilly's orforglipron in phase 2

Source: ADA

The results could leave the door open for a new entrant, Pfizer, which is expected to unveil phase 2 obesity data on two oral GLP-1s, danuglipron and lotiglipron (PF-07081532), this year. That company needs to clear the bar Lilly has just set to become an obesity contender.

Pfizer will have a choice to make between its two projects, although in reality the once-daily lotiglipron needs to win out over twice-daily danuglipron for the group to get a proper crack at this market. The mid-stage obesity study of the former is set to complete in November, and is testing lotiglipron dosed up to 260mg per day.

It would seem unwise to count out the diabetes and obesity specialist Novo Nordisk, though. The Danish group is ahead of both Lilly and Pfizer, recently reporting phase 3 obesity data on oral semaglutide – the active ingredient in Rybelsus, which is approved for type 2 diabetes.

But Rybelsus must be taken on an empty stomach with a specific amount of water, and Lilly and Pfizer have contended that their projects will avoid such requirements.

The table below shows the long-term efficacy that Lilly will be aiming at with orforglipron. As always, care should be taken when comparing across trials. 

Huge figures have been attached to the obesity market – Pfizer itself has said GLP-1s could make $90bn by 2030 – so there should be room for several players, both oral and injectable. But each group will hope to get the biggest possible slice of the pie, and that will depend on the data. 

Setting the bar in obesity: the battle of the GLP1s
Project Wegovy, Novo Nordisk Oral semaglutide, Novo Nordisk Mounjaro, Lilly
Trial Ph3 Step 1 Ph3 Oasis-1 Ph3 Surmount-1
Route of admin SC injection Oral   SC injection
Dose, schedule 2.4mg once weekly 50mg QD 15mg once weekly
Timepoint 68wks 68wks 72wks
Placebo-adjusted weight loss from baseline (%) 12.5 12.7 17.8
Source: ADA abstract, NEJM articles & company release.

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