Amid an outpouring of obesity data Monday, Wave Life Sciences and Structure Therapeutics were among the biotechs jockeying to set their weight loss assets apart in an increasingly crowded field as both companies saw their respective shares soar in early trading.
For Wave, interim results from a phase 1 study have emboldened the company’s belief that its small interfering RNA (siRNA) candidate, WVE-007, could offer comparable weight loss to GLP-1 drugs without the associated muscle loss.
And, in Structure’s case, the San Francisco-based biopharma is preparing to ship its oral GLP-1 receptor agonist into phase 3 testing thanks to midstage data the company’s CEO believes demonstrate “best-in-class” potential.
Both biotechs are releasing their readouts into an increasingly busy environment for next-gen obesity drug development, dominated by incumbent metabolic players Novo Nordisk and Eli Lilly, as well as notable clinical-stage challengers like Viking Therapeutics.
Meanwhile, China-based Ascletis Pharma also took part in Monday’s weight loss data blitz, emphasizing a potential tolerability edge in new phase 2 data on its oral GLP-1 obesity candidate ASC30.
Riding the wave to phase 2
Looking at Wave’s interim phase 1 results, the company reported data at the three-month mark after patients received either placebo or a single 240-mg subcutaneous dose of WVE-007, an experimental siRNA drug with a unique delivery system. Wave has engineered WVE-007 to silence INHBE mRNA, which the biotech has highlighted as an “obesity target with strong evidence from human genetics.”
In the trial, the single dose of WVE-007 helped patients reduce their visceral fat by 9.4% and achieve a 4.5% reduction in total body fat, or around 3.5 pounds, all while charting a 3.2% increase in lean mass, Wave said in a Dec. 8 press release. By comparison, no statistically significant changes from baseline were observed in the placebo cohort, which charted a 0.2% reduction in visceral fat, a 0.5% reduction total body fat and a 2.3% increase in lean mass.
Regarding the observed change in total body weight among patients who received Wave’s RNA-based drug, the biotech noted that the “loss of total fat was offset by the gain in lean mass (primarily consisting of muscle) at this interim assessment in this patient population.”
Wave’s data are “[o]verall very positive,” analysts at Mizuho Securities wrote in a note to clients Monday. The team noted that the data reflect the lowest dose of WVE-007 “and at an early time point,” speculating that the medicine’s overall efficacy stats will creep higher in time.
The Mizuho team further stressed that Wave’s drug “completely spared” patients’ lean mass, which they argued differentiates the asset from GLP-1 drugs and showcases that its mechanism works as intended.
Wave’s phase 1 trial, dubbed INLIGHT, has enrolled more than 100 participants who have obesity or are overweight but are otherwise healthy, the company said. Notably, the trial did not have participants make any diet or exercise modifications for the duration of the study.
In addition to its candidate’s potential muscle loss advantage, Wave also figures that its therapy could potentially be dosed far less frequently than GLP-1 comparators. This translated into a major jump in shares, by 116% at 10:30 a.m. ET Monday.
“Today’s update demonstrates the tremendous potential of WVE-007 to transform the obesity treatment paradigm, addressing the biggest disadvantages of GLP-1s: fat loss at the expense of muscle, poor tolerability, including GI and other side effects, along with frequent dosing,” Paul Bolno, M.D., Wave’s CEO, said in a statement.
“These data affirm WVE-007’s significant potential to provide a meaningful treatment for the over one billion people living with obesity, as a once to twice-yearly monotherapy, add-on therapy to incretins, or maintenance therapy post incretin treatment, and planning for Phase 2 trials in these settings is underway,” Bolno continued.
In the early-stage INLIGHT trial, Wave has fully dosed cohorts across 240-mg, 400-mg and 600-mg WVE-007 treatment arms, with successive readouts expected through 2026, the company noted in Monday’s release.
Additionally, the biotech is now “actively planning” phase 2 studies for its candidate as both a monotherapy and as an add-on to incretin drugs in populations with a higher body mass index and related comorbidities. Wave is also planning to assess WVE-007 as a maintenance therapy after patients have stopped treatment with an incretin therapy, such as a GLP-1.
Structure challenges giants with new data
Over to Structure, the clinical-stage small molecule specialist is hoping to stand out among a swelling number of drugmakers advancing oral GLP-1s for weight loss.
Also Monday, the biotech posted that a 120-mg dose of its experimental GLP-1 receptor agonist aleniglipron—taken once daily by mouth—helped patients chart a placebo-adjusted average weight loss of 11.3% in its phase 2b Access study. Those results came at the trial’s 36-week mark, at which point 10.4% of patients across all active arms had quit the study due to adverse events, Structure said in a release.
Structure noted that its medicine appeared to have a tolerability profile on par with other GLP-1 receptor agonists, plus a “compelling off-target safety profile,” which together have convinced the company to move aleniglipron into late-stage studies, likely by the middle of next year.
“The topline results presented today show that aleniglipron is differentiated and delivered clinically meaningful, competitive and dose-dependent weight loss with a safety profile appropriate for chronic use in a disease that impacts millions of people,” Raymond Stevens, Ph.D., Structure’s chief executive, said in a statement.
“For the higher doses, the observed weight loss data at 36 weeks with no weight loss plateau is potentially best-in-class for oral small molecule GLP1s,” Stevens continued. “Most importantly, these findings provide comprehensive information to move into Phase 3 development and reinforce aleniglipron’s potential to become a backbone oral small molecule therapy for obesity—one that is accessible, scalable, and combinable.”
Structure’s phase 2b trial ran for 36 weeks and enrolled 230 adults with obesity or who are overweight and had at least one weight-related comorbidity. Patients received either placebo or a final 45-, 90- or 120-mg dose of aleniglipron once a day, the company explained.
All three therapeutic doses of aleniglipron hit statistical significance on the study’s primary endpoint and all key secondary goals, Structure noted. The biotech's shares had soared by more than 107% by midmorning Monday.
Following the commercial success of Novo’s Wegovy and Lilly’s Zepbound, scores of drugmakers have thrown their hats into the obesity drug development ring. Currently, Novo and Lilly are leading the pack in advancing potential oral GLP-1s for obesity, with Novo anticipating an FDA decision on its version of Wegovy in a pill before the end of the year.
Aside from Structure and Wave's data drops, Ascletis on Monday rolled out results on its own obesity contender, the oral GLP-1 agonist ASC30, in a phase 2 study of 125 patients in the U.S. After 13 weeks in the trial, Ascletis’ drug was linked to placebo-adjusted average weight reductions of 5.4%, 7% and 7.7%, respectively. All three of those readouts qualified as statistically significant, Ascletis noted in a Dec. 8 release.
In particular, Ascletis posited that its drug could edge out potential rivals when it comes to gastrointestinal tolerability.