Two key GLP-1 updates came out in the last week, both on small molecules: Pfizer's update on danuglipron, and Roche's topline results yesterday on CT-996, which caused shares of competitors to drop sharply - here's the recap:

Roche’s announcement yesterday moved markets - Roche stock rose 7%, while those of several competitors, including Eli Lilly, Novo Nordisk, and smaller biotechs developing GLP-1s declined, some by double digits.

So what were the results?

Topline data for oral CT-996 showed placebo-adjusted weight loss of 6.1% within 4 weeks.

The amount of weight loss per se wasn't notable - but the speed with which it occurred was.

Given weight loss tends to continue the longer the treatment lasts, follow-up data will almost certainly demonstrate even greater weight loss, and the strong showing in the first 4 weeks sets CT-996 up for promising results.

To put things in perspective, Lilly’s most advanced once-daily oral GLP-1 candidate, orforglipron, achieved weight loss of 7.1-12.4% after 26 weeks depending on dose.

Meanwhile, another early oral candidate, Novo’s Amycretin, achieved 12% placebo-adjusted weight loss after 12 weeks in early phase 1 results.


Stepping back, Roche's data is impressive, but there are 2 caveats:

First, this was a relatively small scale Phase 1 study - the two parts that have been completed so far had 40 participants and 25 participants, respectively.

Second is timing - Roche will advance the drug into Phase II development, but is still behind not only Lilly and Novo, which both have once-daily oral GLP-1s in phase 3 trials, but also Pfizer,Structure Therapeutics, andKallyope(among others), which all have small-molecule weight loss medicines in Phase 2 trials.

Pfizer’s announcement last week was also notable given the twists and turns it has had in developing its obesity portfolio:


Pfizer has 3 candidates in its pipeline related to obesity & GLP-1s: danuglipron, PF-07976016, and PF-06954522 (indicated for T2D).

The company hit a speedbump last year when it discontinued trials of lotiglipron following concerns of elevated liver enzymes in patients. It also discontinued twice-daily danuglipron formulations given high levels of side-effect induced dropouts, which exceeded 50%.

Last week, Pfizer announced it would advance its chosen once-daily formulation into dose optimization studies later this year.

While that is a positive sign, it will be key to see the level of weight loss achieved, as well as if the side effects - mostly nausea/GI related - are indeed more tolerable than the earlier twice-daily formulation.

Overall - it’s clear Lilly and Novo will be first to market with once-daily oral weight loss medicines.

However, given the sheer size of the market - estimated to grow to $100B+ by the early 2030s, the prize for fast followers will still be substantial.