Wave Life Sciences announced on Mar. 26 that its investigational RNA interference therapy for obesity showed mixed results in an early-stage clinical trial, leading to a significant drop in the company's stock price. The biotech's shares opened at $5.59, down 54% from the previous close.
The company is testing its siRNA therapeutic WVE-007 in the INLIGHT study, which includes both Phase 1 and planned Phase 2a segments targeting overweight or obese adults. The latest results are from the Phase 1 single-ascending dose portion of the trial.
At six months, participants receiving a single 240-mg dose of WVE-007 saw a statistically significant reduction of visceral fat by 14.3%, up from a previous three-month figure of 9.2%. These patients also experienced a decrease in total fat mass by 5.3%, an increase in lean mass by 2.4%, and reductions in waist circumference and body weight at six months.
However, data from participants given a higher, single-dose of 400 mg were less encouraging at three months: visceral fat loss was only about 5%, with minimal changes to lean mass and total fat loss below one percent. Leerink Partners said Thursday that "Investors are likely discouraged by the 400 mg data at 3 months, which look similar on visceral fat as 240 mg and not as good on total fat and lean mass, though there appear to be some differences in the baseline BMI and body composition of this cohort that could explain some of these observations," according to Reuters.
Wave stated that those enrolled in the higher-dose group had lower initial body mass index (BMI) and healthier levels of visceral fat compared to other cohorts, potentially affecting outcomes. A posthoc analysis indicated a reduction in visceral fat similar to what was seen with the lower dose group.
Despite market reaction, some analysts remained positive about WVE-007's prospects. Oppenheimer analyst Cheng Li said Thursday: "We would be buyers on any weakness, as the results further support the clean safety profile and once/twice-yearly dosing of WVE-007." Analysts at Mizuho Securities also described recent findings as "good data," adding that reducing visceral fat while maintaining lean mass is encouraging for differentiation among obesity treatments.
Looking ahead, Wave plans to start enrolling patients with higher BMI and related health conditions for its upcoming Phase 2a study segment during the second quarter. The company will also explore using WVE-007 alongside incretin-based therapies or after such treatments.
