Viking's VK2735 Maintains Up to 97% of Weight Loss With Monthly and Biweekly Dosing
核心洞察
Viking Therapeutics reported topline results from its Phase 2 maintenance study of VK2735, a dual GLP-1/GIP agonist, in approximately 180 adults with obesity (搜索).
After 21 weeks of weekly dosing, participants lost 16% to 19% of body weight versus approximately 0% for placebo, with no plateau observed.
Switching to every-other-week dosing preserved up to 97% of weight loss and monthly dosing preserved up to 90%, compared with 61% for placebo.
Viking Therapeutics has reported positive topline results from the Phase 2 VK2735-102 maintenance study, showing that adults with obesity (搜索) who transitioned from weekly dosing of the dual GLP-1/GIP agonist VK2735 to less frequent regimens retained most of their weight loss over an additional 12 weeks. The company said the data support the viability of monthly and every-other-week subcutaneous maintenance dosing, an approach aimed at improving long-term adherence to incretin-based obesity therapy.
Induction Phase Results
The randomized, double-blind, placebo-controlled trial enrolled approximately 180 adults with obesity (搜索) (BMI at or above 30 kg/m2) who were otherwise healthy. All participants received weekly subcutaneous VK2735 or placebo for 21 weeks. Starting at Week 3, VK2735 doses were escalated every two weeks to final doses of 15.0 mg, 17.5 mg, 20.0 mg, or 22.5 mg.
Weight loss after 21 weeks ranged from approximately 16% to 19% across VK2735 cohorts, compared with approximately 0% for placebo (p<0.0001 versus baseline and placebo for all cohorts). Weight loss was progressive in each cohort, with no evidence of plateau through 21 weeks of weekly dosing. In the combined treatment groups, the proportions of participants achieving 5%, 10%, 15%, and 20% weight loss were 98%, 90%, 65%, and 32%, respectively, versus 13%, 0%, 0%, and 0% for placebo (p<0.01 versus placebo for each).
An exploratory control cohort that continued weekly VK2735 17.5 mg (n=13) demonstrated mean weight loss of 21.7% from baseline at Week 33 (p<0.0001 versus baseline), compared with 0.3% weight gain for placebo (p<0.0001 versus placebo). Weight loss in this cohort remained progressive through 33 weeks with no plateau observed.
Maintenance Phase Outcomes
After the 21-week induction period, participants on weekly VK2735 were randomized to monthly (every four weeks) or every-other-week maintenance regimens for 12 weeks. Subjects on every-other-week dosing maintained up to 97% of the mean weight loss achieved during induction, compared with 61% for those randomized to placebo (p<0.0001 versus placebo). Participants on monthly regimens maintained up to 90% of their induction weight loss, also compared with 61% for placebo (p=0.0002 versus placebo). Separation from placebo was observed as early as four weeks after the transition from weekly dosing in both groups.
In the pooled every-other-week cohort, average weight loss maintenance was 90%, while the monthly dosing group averaged 85%, according to BioPharma Dive.
Tolerability During Maintenance
VK2735 showed an encouraging safety and tolerability profile during the 12-week maintenance window. Rates of gastrointestinal adverse events including vomiting, nausea, diarrhea, and constipation were not meaningfully different from placebo. Discontinuation rates, including those due to adverse events, were low during both phases. One discontinuation due to an adverse event occurred during the induction phase, one in the every-other-week group, and three in the monthly cohort.
During induction, one subject (1%) discontinued VK2735 due to an adverse event. The most common adverse events were gastrointestinal, characterized as mild and consistent with GLP-1 receptor (搜索) activation. Despite an accelerated two-week titration schedule, rates of common GI events were similar to those reported in the prior Phase 2 study, which used three-week titration steps. Among combined treatment groups, GI-related adverse event incidence was low and declined over time.
Dosing Flexibility and Clinical Rationale
"The results of our innovative maintenance dosing study continue to demonstrate the significance of VK2735's unique and differentiated half-life and PK profile, which appear to enable an effective new approach to achieving and maintaining the weight loss goals of patients living with obesity (搜索)," said Brian Lian, Ph.D., chief executive officer of Viking.
Lian said the dose-ranging study demonstrated the potential viability of extended dosing approaches for maintenance following induction with an incretin-based therapy, and that tolerability during maintenance may allow evaluation of higher doses and less frequent dosing for both maintenance and induction.
Louis Aronne, MD, FACP, former president of The Obesity (搜索) Society, said the results provide a basis for improved dosing flexibility for clinicians and patients. "The cardiometabolic benefits of maintaining 75% or more of a patient's weight loss are becoming clearer, and these results demonstrating robust maintenance with reduced and less frequent doses are supportive of maintaining people within that margin through either monthly or every-other-week administration," Aronne said. Aronne is a paid consultant to Viking Therapeutics.
Study Design and Next Steps
The maintenance study's objectives were to evaluate the safety, tolerability, and pharmacokinetic profile of VK2735 under monthly, every-other-week, and weekly subcutaneous regimens. Exploratory endpoints assessed change in body weight from baseline and from Week 21 to the end of study at Week 33.
VK2735 is being developed in both subcutaneous and oral formulations for obesity (搜索) and other metabolic disorders, and is currently being evaluated in Phase 3 clinical studies for obesity. Viking plans to explore oral maintenance dosing regimens in an upcoming part 2 of the current study. The company's broader pipeline includes VK3019 (搜索), an amylin receptor agonist, VK2809, an orally available thyroid hormone receptor beta agonist for metabolic and liver disease, and VK0214 for X-linked adrenoleukodystrophy (搜索).
GLP-1 receptor (搜索) activation has been shown to decrease glucose, reduce appetite, lower body weight, and improve insulin sensitivity in patients with type 2 diabetes (搜索), obesity (搜索), or both. Semaglutide, marketed as Ozempic, Rybelsus, and Wegovy, is an approved GLP-1 receptor agonist. Tirzepatide, a dual GLP-1/GIP receptor (搜索) agonist marketed as Mounjaro and Zepbound, is also FDA approved. Viking's approach tests whether less frequent maintenance dosing can address adherence challenges associated with chronic GLP-1 therapy.