Roche’s once-daily oral weight loss pill helped Phase 1 subjects lose up to 7.3% of their body weight within one month, which is less than competitors who measured the performance of their oral options — albeit over a longer time frame.
The new data presented at the European Association for the Study of Diabetes annual meeting Wednesday detailed how the company’s once-daily pill, CT-996, performed in patients with obesity but without type 2 diabetes. The study was primarily testing the safety and tolerability of the drug, particularly on a very fast titration program, in addition to total weight loss over four weeks.
Patients in the highest dose cohorts ascended to 120 mg over five dose increments within three weeks, beginning at 10 mg and sometimes increasing doses in a matter of days. It allowed Roche to quickly assess the tolerability and whether a certain dose immediately caused more troublesome toxicity like signs of liver damage.
In one of the two cohorts where patients increased to the highest dose in the study, patients lost an average of 7.3% of their body weight. In the other high-dose cohort, where patients had even higher leaps in doses before reaching the maximum amount, patients lost 5.8% of their body weight.
The most common side effects were gastrointestinal-related, like nausea and constipation, particularly in the higher dose cohorts. But the rates were lower among patients that had a slightly smoother ascension in dose.
Manu Chakravarthy, head of cardiovascular, renal and metabolism product development at the Swiss pharma, said the data give the company “a lot of excitement” about the oral program.
Manu Chakravarthy“You’re getting the same level of tolerability that you’re seeing with other molecules, despite this very steep titration, but yet we’re getting a very high level of efficacy,” he said.
Roche’s presentation came less than a day after Novo Nordisk unveiled early data of its own pill amycretin, finding that patients receiving the drug once a day lost an average of 10.4% of their body weight after three months.
Chakravarthy said it’s “amusing” when these new candidates are assessed by small percentage-point changes in weight loss, arguing that the pharmacokinetics of CT-996 reinforce a once-daily regimen over competitors.
“A lot of other molecules, when you look at it — they say it’s once daily — but when you actually look at the plasma half-life, it’s not consistent with once daily,” he said, prompting him to question whether some companies are “leaving efficacy on the table.”
Chakravarthy rationalized CT-996’s swift titration process by saying the point was to “pressure test” the safety profile. Despite the GI side effects, there were no severe treatment-emergent side effects and no one discontinued the study due to the drug. The cardiometabolic executive expects that the drug will perform even better — both on efficacy and tolerability — in a mid-stage study that’s longer and does not have such a rigorous dosing process.
Other side effects, like lean muscle loss, were not tracked in this study but will be in an upcoming Phase 2. That’s expected to launch later in 2025 after Roche completes part 3 of the Phase 1 study, testing CT-996 in patients with both type 2 diabetes and obesity.
The oral pill was acquired in Roche’s $2.7 billion purchase of Carmot Therapeutics, which included a dual-acting injectible, CT-388. Additional Phase 1 data of that asset were reported on Tuesday, showing that patients at the highest dose lost nearly an average of 19% of their body weight at 24 weeks. That asset has already begun a Phase 2 study, though Chakravarthy wouldn’t commit to a timeline for interim data.