45% of Patients Achieve Over 20% Weight Loss with Roche's GLP-1/GIP Dual Agonist CT-388

On July 15, Roche announced the Phase Ib clinical data of its investigational GLP-1/GIP small molecule agonist CT-388, showing that the higher dose had not yet reached the weight loss peak at 6 months.

An abstract to be presented at the annual meeting of the European Association for the Study of Diabetes in Madrid in September shows,CT-388’s weight loss effect at 24 weeks has not plateaued, which means it may achieve better results than the previously announced average weight loss rate of 18.8%.

In December 2023, Roche announced the signing of a definitive acquisition agreement with Carmot Therapeutics, agreeing to acquire the latter for $3.1 billion, thereby obtaining CT-388.

Roche had previously been developing the GLP-1 receptor agonist drug Taspoglutide, which entered Phase 2 clinical trials in 2008. However, by 2011, Roche abandoned the candidate drug due to its side effects.

This acquisition also marks Roche's official return to the GLP-1 field.

Carmot Therapeutics has three main GLP-1 candidate drugs in clinical-stage development for subcutaneous and oral administration, with CT-388 being the most advanced product.

CT-388 is a once-weekly subcutaneous injectable dual GLP-1/GIP receptor agonist in development for the treatment of obesity and type 2 diabetes (T2D).

On May 16, Roche disclosed the results of the Phase I clinical trial of CT-388: after 24 weeks,Weekly subcutaneous injection of CT-388 resulted in an average weight loss of 18.8% (after placebo adjustment, p < 0.001);100% of participants receiving CT-388 treatment lost >5% of their body weight, 70% of subjects lost >15%, and 45% of subjects lost >20%.

In addition, CT-388 was well-tolerated, with mild to moderate gastrointestinal-related adverse events being the most common, consistent with the class of incretin-based drugs to which CT-388 belongs. All subjects who were in a pre-diabetic state at baseline returned to normal blood glucose levels after 24 weeks of treatment with CT-388, whereas subjects receiving placebo showed little change in their blood glucose status during the same period.

The earlier announced data was CT-3884's weight loss data at week 4, with a weight loss result of 8.4% at that time.

Manu Chakravarthy, Roche's Senior Vice President and Global Head of Cardiovascular, Renal and Metabolism Product Development, said in an interview that the company plans to launch a Phase II study later in 2024 to evaluate weight loss as well as other outcomes such as improvements in cardiovascular disease and type 2 diabetes.

Chakravarthy also added that the Phase II study will be used to further refine the dosing regimen.

Patients receiving CT-388 treatment started with a dose of 5 mg. In one single-arm study, the dose was increased to 8 mg, while in another single-arm study, it was escalated to 22 mg. No treatment-related discontinuations were reported in these studies. More data on a higher dose of 24 mg is expected to be available later in 2024.

Jefferies, a well-known investment bank, predicts that the drug will be launched in 2029 and reach a peak sales volume of $4 billion.

The early clinical weight loss data of Roche's CT-388 has added fuel to the already red-hot GLP-1 weight loss drug track, but Roche is not the only "fire starter"—there's also Pfizer.

In 2023, Pfizer hit roadblocks with two GLP-1 oral small molecule agonists, discontinuing the clinical development of Lotiglipron and Danuglipron (twice daily).

After the setback, Pfizer decided to give it another try.

On July 12, Pfizer announced that based on the pharmacokinetic results from the ongoing Phase 1 trial, the company has selected and finalized a preferred extended-release formulation for the oral GLP-1R agonist Danuglipron (PF-06882961) for once-daily dosing.

Pfizer plans to initiate a dose optimization study for this sustained-release formulation in the second half of 2024 to evaluate the efficacy and safety of multiple doses, providing reference for registrational trials.

This study is a randomized, open-label clinical trial designed to evaluate the pharmacokinetics and safety of Danuglipron oral immediate-release and oral extended-release formulations in healthy adults. The results indicate that the new formulation allows for once-daily dosing of Danuglipron. Its safety profile is consistent with previous studies, with no observed elevation in liver enzymes.

Prior to this, Danuglipron was administered twice daily. In December 2023, the Phase IIb study of Danuglipron (twice daily) for the treatment of obese adult patients without type 2 diabetes reached its primary endpoint.

Data showed that at Week 26 of treatment, the weight changes in all dose groups of Danuglipron were significantly greater compared to the placebo group (-4.8%~-9.4% vs. +0.17%). By Week 32 of treatment, the weight changes in all dose groups of Danuglipron remained significantly greater than those in the placebo group (-6.9%~-11.7% vs. +1.4%). After placebo adjustment, the average weight reduction in the Danuglipron groups was -5%~-9.5% at Week 26 and -8%~-13% at Week 32.

Currently, the weight-loss drug sector has formed a bipolar multi-strong pattern dominated by Novo Nordisk and Eli Lilly. However, under the huge market demand, latecomers still have opportunities. We look forward to more breakthrough GLP-1 product data from R&D powerhouses like Roche and Pfizer, and believe that "there will be other winners emerging."

Source: https://endpts.com/roche-details-early-obesity-data-from-glp-1-gip-agonist-plans-for-phase-2-study-this-year/