A Viking Therapeutics drug that hits two targets to spark weight reduction achieved the targets of a carefully watched mid-stage scientific trial, however with outcomes that additionally present many sufferers stopped the remedy as a result of gastrointestinal issues, which traders considered as denting the each day tablet’s prospects in a rising discipline of oral weight problems medication contenders.
All 5 doses of the drug, VK2735, led to statistically vital variations in comparison with each baseline measures and placebo within the 13-week, dose-finding Section 2 research, Viking mentioned Tuesday. The best weight discount — a mean of 12.2%— was noticed on the highest dose, 120 mg. The preliminary outcomes present reductions in physique weight that have been progressive in any respect doses all through the research. This weight reduction didn’t plateau as of 13 weeks, suggesting sufferers would proceed shedding weight with longer dosing.
Viking additionally reported that as much as 97% of members within the research drug arms achieved 5% or better weight reduction, in contrast with simply 10% of sufferers within the placebo group, a statistically vital end result that met a secondary aim of the research. As much as 80% of sufferers who obtained VK2735 achieved 10% or better weight reduction in contrast with 5% of these within the placebo group.
VK2735 is designed to focus on and activate two intestine receptors, GLP-1 and GIP — the identical targets hit by Eli Lilly’s blockbuster once-weekly injectable drug, Zepbound. Gastrointestinal issues, similar to nausea and diarrhea, are a identified facet impact of metabolic medicines on this drug class. Such hostile results lead many sufferers to cease taking the medication.
Viking is creating subcutaneously injectable and oral formulations of VK2735. The oral model would supply a much less burdensome dosing possibility in comparison with weekly injections. Drugs are additionally envisioned as a possible upkeep remedy after sufferers obtain their goal weight reduction with an injectable weight problems drug. However for any weight problems tablet to fill that function, an appropriate tolerability profile is crucial.
Within the Section 2 check of oral VK2735, discontinuation charges have been dose dependent. The best dose group had the very best discontinuation fee with 38% of members on this cohort stopping remedy early in comparison with an 18% discontinuation fee within the placebo arm. Nausea was the most typical hostile occasion, reported in 58% of sufferers who obtained the research drug. This facet impact was reported in 48% of those that obtained a placebo. Viking mentioned a lot of the nausea was characterised as delicate or average. Vomiting was reported in 26% of sufferers who obtained VK2735, in contrast with 10% of these within the placebo group. The corporate mentioned the gastrointestinal issues have been typically noticed early in remedy and decreased in frequency upon repeated dosing.
The Section 2 research included an exploratory cohort designed to evaluate VK2735 in weight reduction upkeep. On this group, members have been quickly titrated to 90 mg each day doses. After 4 weeks, sufferers obtained 30 mg each day doses for seven weeks. Viking reported this group confirmed fast and progressive weight reduction by the 90 mg remedy interval. This weight reduction was maintained following the transition to the decrease each day dose.
Shares of Viking opened Tuesday at $25.99 every, down greater than 38% from Monday’s closing worth. William Blair analyst Andy Hsieh acknowledged the tolerability points and better discontinuation charges that have been worse than the encouraging Section 1 knowledge reported for the tablet final yr. However in a observe despatched to traders, Hsieh identified that the burden loss marks posted by VK2735 outpace Section 2 outcomes for each Eli Lilly’s oral GLP-1 drug, orforglipron, as effectively the excessive dose of Novo Nordisk’s oral model of its GLP-1 peptide drug semaglutide. Earlier this month, Eli Lilly reported Section 3 knowledge for orforglipron that upset analysts on measures of weight reduction and tolerability, leaving the door open to smaller contenders, similar to Viking.
Leerink Companions analyst Thomas Smith mentioned in a analysis observe that the burden loss achieved by Viking’s tablet is aggressive with Lilly’s orforglipron, however variations in how the medication have been titrated of their respective research make cross-trial comparisons tough. Within the Lilly drug’s Section 2 check, titration various with sufferers within the excessive dose arm reaching that dose by week 12. By comparability, sufferers who obtained the excessive dose of Viking’s drug reached that dose degree by week six. In a Tuesday convention name, Viking administration mentioned the corporate plans extra gradual titration shifting ahead, which Smith mentioned will supply the potential to optimize efficacy and tolerability.
Each Hsieh and Smith see the Viking inventory sell-off as overblown. Whereas the tolerability profile for VK2735 is worse in Section 2 in comparison with Section 1, William Blair sees the 30 mg dose having a placebo-like profile. The agency believes this dose may very well be chosen because the potential upkeep dose within the drug’s pivotal check. Given the upper prices related to producing the upper doses, Hsieh believes it’s unlikely Viking will advance the 2 greater doses to pivotal testing. He added that tolerability may be mitigated and improved by increasing the titration to 4 weeks within the Section 3 research versus two weeks within the shorter Section 2 trial, named VENTURE-Oral. Hsieh is looking forward to an upcoming Section 2 grasp protocol research that can discover the transition from injectable VK2735 to upkeep remedy with as soon as month-to-month injections or each day doses of the oral formulation of the Viking drug.
“On condition that people searching for remedy for power weight administration are possible searching for a fast diploma of preliminary weight reduction, it’s our view that subcutaneous injections will proceed to be most popular through the preliminary course of remedy,” Hsieh mentioned. “Primarily based on the VENTURE-Oral research, 30 mg or 60 mg are each well-positioned within the upkeep setting, which we imagine represents the most important [total addressable market] within the weight problems market pushed by the chronicity of the situation.”
The marketplace for potential oral weight problems medication is aggressive. Apart from the Eli Lilly and Novo Nordisk tablets, Construction Therapeutics is in mid-stage scientific growth with an oral small molecule agonist of GLP-1. Roche is in early scientific growth with an oral GLP-1 drug codenamed CT-996, which comes from its $2.7 billion acquisition of Carmot Therapeutics. Startups are additionally a part of the combo. Response Prescribed drugs lately reported encouraging Section 2 knowledge for its twice-daily tablet, which matches after a novel goal referred to as iMTP.
Not all oral efforts weight problems drug efforts have been profitable. Earlier this yr, Pfizer stopped work on an oral small molecule concentrating on GLP-1 after a liver complication emerged in Section 1 testing.
Picture: Martin Barraud, Getty Photos
