Viking felled by dropout rates in oral obesity drug trial
Shares in Viking Therapeutics have lost more than 40% of their value after it reported phase 2 results that showed that its oral weight-loss drug was effective, but was linked to a high rate of treatment discontinuations.
At the most effective dose (120mg), dual GIP/GLP-1 agonist VK2735 helped subjects in the study lose 12.2% of their weight over 13 weeks of follow-up, compared to a 1.3% drop in the placebo group.
That puts the peptide-based drug in the same general ballpark as other oral obesity therapies coming through the pipeline, such as Eli Lilly's GLP-1 drug orforglipron and Novo Nordisk's oral GLP-1 semaglutide and GLP-1/amylin agonist amycretin. Still, investors seem to have been spooked by data showing that 38% of people taking the 120mg dose of VK2735 discontinued treatment.
Drugs that act via the GLP-1 pathway are known to cause gastrointestinal side effects that can make them hard to tolerate. In the VENTURE-Oral Dosing trial data drop, Viking revealed that most discontinuations were a result of nausea, seen in 60% of the 40 patients on the 120mg dose, with 15 cases mild, seven moderate and two severe. A 35% rate of vomiting was also seen in that dose group.
The selloff seemed to stem from concerns that the tolerability profile might prevent Viking from taking the most effective dose forward into phase 3, as well as disappointment that the weight loss achieved was quite as strong as seen in studies of its rivals. At lower daily doses of 15mg to 90mg, VK2375 achieved weight loss of 2.3% to 11.1%.
It's worth noting, however, that the weight-loss achieved with oral therapies is acknowledged to be less than that seen with the current injectable GLP-1-based therapies, and their convenient dosing offers the prospect of early intervention and long-term disease management.
Moreover, Viking also reported results from a maintenance dose cohort in which an initial 90mg dose over four weeks was reduced to a more tolerable 30mg dose over the remainder of the 13-week study, with the results showing the initial weight loss was maintained after the reduction.
Viking's chief executive, Brian Lin, said that "the progressive nature of the weight loss curves suggests the potential for further improvement with longer dosing periods," suggesting that VK2375 could still mount a challenge to rival oral therapies, which have been tested over longer periods of a year or more.
Lin added that the experimental maintenance arm of the study "provides an encouraging signal that supports our belief that transitioning patients from higher doses, injectable or oral, to low oral doses represents a promising approach to weight maintenance therapy. We look forward to exploring this further in an upcoming maintenance dosing study."
