While participants on a lower dose of Wave Life Sciences’ RNA therapy lost 5.3% total fat at the six-month mark, those receiving the higher dose saw a less than 1% drop at three months.
Wave Life Sciences touted body composition improvements in an early-stage study of its investigational RNA interference obesity therapy—but when it came to the higher 400-mg dose, analysts weren’t impressed. At $5.59 apiece when the opening bell rang on Thursday, the biotech was trading 54% lower than its previous closing price.
Oppenheimer analyst Cheng Li stuck by the candidate, however. “We would be buyers on any weakness, as the results further support the clean safety profile and once/twice-yearly dosing of WVE-007,” Li said Thursday, according to Reuters.
Wave is studying its siRNA therapeutic WVE-007 in the INLIGHT study, which includes a Phase 1 single-ascending dose portion in otherwise healthy adults who are overweight or obese, and a Phase 2a section that will look at several doses of WVE-007. Thursday’s readout comes from the Phase 1 portion of the trial.
The results showed that at six months, participants treated with 240-mg WVE-007 shed 14.3% of their visceral fat, a statistically significant improvement from baseline and up from 9.2% at three months. Total fat mass at six months dropped 5.3% while lean mass increased 2.4%. Patients at this dose level also saw a 3.3% reduction in waist circumference and 0.9% decrease in body weight at six months.
However, when it came to three-month data from a 400-mg cohort, analysts appeared to be expecting more, Bloomberg reported Thursday. Participants in this cohort saw 5% visceral fat loss, 0.2% loss of lean mass and total fat loss of less than 1%.
“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,” Leerink Partners said in a Thursday note, Reuters reported.
Wave noted in its press release that this cohort had a leaner baseline body composition, with lower BMI and more participants with healthy levels of visceral fat. The company also noted that a posthoc analysis showed a 7.8% reduction in visceral fat, a result “similar to that observed in the 240 mg cohort.”
The biotech also presented visceral fat-to-muscle ratio, a metric used to quantify body composition, for the 240-mg dose group at six months. A single dose of 240 mg resulted in a 16.5% drop in this ratio—better than what was achieved by a 2.4-mg dose of Novo Nordisk’s semaglutide at six months, according to Wave—a 12.2% decrease from baseline.
Last December, Wave reported a 9.2% reduction in visceral fat at three months with the 240-mg dose, accompanied by a 0.9% increase in lean mass. Truist analysts at the time called the data “impressive.” Wave’s shares crested 80% following the readout.
Despite the stock crash this week, analysts at Mizuho Securities said in a Thursday note that WVE-007 delivered “good data.” The reduction in visceral fat and waist circumference, “while stabilizing lean mass is particularly encouraging, and continues to showcase WVE-007 as a differentiated mechanism for obesity.”
The firm models around $7 billion in peak worldwide sales for WVE-003.
The biotech now plans to begin the Phase 2a portion of INLIGHT in the second quarter, looking to enroll patients with higher body mass index and weight-related comorbidities, according to the Thursday release. The biotech will also run new trials of WVE-007 as part of incretin-based regimens or as a post-incretin therapy.
