An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *

Genentech Announces Positive Phase I Results of Its Oral GLP-1 Receptor Agonist CT-996 for the Treatment of People With Obesity

On July 17, Genentech, a member of the Roche Group, announced positive topline results from two arms of an ongoing multi-part Phase I clinical trial for CT-996, an investigational, once-daily, oral small molecule GLP-1 receptor agonist being developed for the treatment of both type 2 diabetes and obesity. 

The data showed that treatment with CT-996 in participants with obesity and without type 2 diabetes resulted in a clinically meaningful placebo-adjusted mean weight loss of -6.1% within four weeks (p <0.001). The full study data will be presented at an upcoming medical meeting.

“We are pleased to see the clinically meaningful weight loss in people treated with our oral GLP-1 therapy CT-996, which could eventually help patients address both chronic weight management and glycemic control indications,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development. “Following our data for CT-388, this is the second positive readout in less than three months from our growing metabolic pipeline, which includes both oral and injectable options to address patients’ needs across a spectrum of related diseases.”

CT-996 was well tolerated, with mostly mild or moderate gastrointestinal-related adverse events, consistent with the safety profile of the incretin drug class. There were no treatment discontinuations related to the study drug.¹ The study results also showed that blood levels of CT-996 were largely unaffected either during fasting or after a standardized high-fat meal. Thus, CT-996 could potentially be dosed without regard to meal timing, thereby affording greater dosing flexibility for patients.¹ Based on the study data, CT-996 is anticipated to be used not only as a therapy for achieving glycemic control and inducing weight loss, but also potentially for oral weight maintenance therapy following weight loss induced by injectables.

Despite numerous approved treatments, the trajectory for people with obesity or its comorbidities has not changed significantly; these conditions remain underdiagnosed and undertreated so their impact on society continues to grow.⁵ Oral and injectable incretin modalities are critical to address the high unmet need. They may not only offer broader access to patients living with obesity, but together, they could also support the prevention of obesity-related comorbidities or complications such as type 2 diabetes and heart disease among many others.

Genentech’s Vabysmo Showed Extended Durability, Continued Efficacy and a Consistent Safety Profile in Long-Term DME Study

Also on July 17, the company announced new, four-year data from the RHONE-X extension study. The study met all primary endpoints, showing that Vabysmo^® (faricimab-svoa) was well tolerated in people with diabetic macular edema (DME) who received treatment for up to four years.

Exploratory results from the long-term study showed that Vabysmo continued to preserve vision, dry retinal fluid that can impair sight and allow extended time between treatments in people with DME. These data were presented in a late-breaking oral presentation at the American Society of Retina Specialists (ASRS) 2024 Annual Meeting in Stockholm, Sweden.

“These four-year data build on our pivotal studies and reinforce Vabysmo’s potential to become standard of care treatment for diabetic macular edema (DME), which affects 29 million people worldwide,” said Garraway. “We are especially pleased to see that 9 out of 10 patients showed no sign of DME after four years of treatment with Vabysmo, which is an incredible long-term outcome for people living with this condition.”

The RHONE-X study is the largest long-term extension dataset in DME, a leading cause of vision loss in people with diabetes.

“I have been using Vabysmo as a first-line treatment for all the approved indications, including diabetic macular edema, and the positive long-term safety and efficacy results from the RHONE-X study are consistent with my clinical experience for over two years,” said study investigator Arshad M. Khanani, MD, director of clinical research at Sierra Eye Associates and clinical professor at the University of Nevada, Reno, who presented the data at ASRS.

During RHONE-X, all participants were treated with Vabysmo on a personalized treat-and-extend regimen, where the time between Vabysmo treatments could be increased based on retinal fluid levels and visual acuity. Results of the exploratory analysis showed that at the end of four years nearly 80% of participants treated with Vabysmo had extended their treatment intervals to every three or four months. Additionally, people treated with Vabysmo maintained the vision improvements and sustained the drying of retinal fluid they achieved during the initial Phase III studies (YOSEMITE and RHINE). In a pre-specified exploratory endpoint, more than 90% of people treated with Vabysmo achieved absence of DME, defined as central subfield thickness (CST) less than 325 microns. CST is a measure of swelling from fluid in the back of the eye caused by unstable, leaky blood vessels; reducing CST indicates retinal drying.

To date, Vabysmo is approved in nearly 100 countries for DME and wet, or neovascular, age-related macular degeneration (AMD). It is also approved in several countries, including the U.S. and Japan, for the treatment of macular edema following retinal vein occlusion. More than four million doses of Vabysmo have been distributed worldwide since its initial U.S. approval in 2022.

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