Side effects make Vikings' oral obesity drugs a tough medicine for investors to swallow
A Viking therapy that meets two target weight loss goals achieved the goal of a closely watched mid-term clinical trial, but the results also suggest that many patients have stopped treatment due to gastrointestinal problems, which investors believe is suppressing the prospect of daily medication in the field of increasing competitors for oral obesity drugs.
Viking said Tuesday that all five doses of VK2735 for the drug brought statistically significant differences in the Phase 2 study found at 13 weeks, compared with baseline measures and placebo. At the highest dose of 120 mg, maximum weight loss was observed (mean 12.2%). Preliminary results show that the weight loss has gradually increased throughout the study. This weight loss was stable underdeficiency as of 13 weeks, suggesting that patients will continue to lose weight longer.
Viking also reported that 97% of participants who studied drug arms lost 5% or higher, while only 10% of patients in the placebo group, a statistically significant result that met the secondary goals of the study. Among patients receiving VK2735, up to 80% of patients lost 10% or more in weight, compared with 5% in the placebo group.
VK2735 is designed to target and activate two gut receptors GLP-1 and GIP – the same target that Eli Lilly once hit on a weekly injectable drug Zepbound. Gastrointestinal problems, such as nausea and diarrhea, are known side effects of metabolic drugs in this drug category. This adverse reaction has caused many patients to stop taking medication.
Vikings are developing subcutaneous injection and oral formulas for VK2735. The oral version has a smaller dosage option than weekly injections. The pill is also considered a potential maintenance treatment after patients achieve target weight loss using injectable obesity medications. However, for any obesity pill to fill that role, an acceptable profile of tolerance is critical.
In a phase 2 test of oral VK2735, the rate of discontinuation depends on the dose. The highest dose group had the highest rate of discontinuation, while 38% of participants who stopped treatment in the placebo group had stopped treatment. Nausea is the most common adverse event, reported in 58% of patients receiving the study drug. It is reported that 48% of people who received the placebo have side effects. Viking says most nausea are mild or moderate. It was reported that 26% of patients receiving VK2735 vomited, compared with 10% of patients in the placebo group. The company said gastrointestinal problems are usually observed early in the treatment and the frequency decreases after repeated doses.
The Phase 2 study included an exploratory cohort designed to evaluate VK2735 that maintained weight loss. In this group, participants quickly titrated to a daily dose of 90 mg. Four weeks later, the patient received a dose of 30 mg per day for 7 weeks. Viking reported that during the 90 mg treatment, this group showed rapid and progressive weight loss. Keep weight loss after transitioning to the lower dose.
Vikings stock opened at $25.99 on Tuesday, down more than 38% from Monday's closing price. William Blair analyst Andy Hsieh acknowledged that tolerance issues and higher deactivation rates are worse than the encouraging first phase data reported by the pill last year. However, in a note sent to investors, HSIEH noted that VK2735 posted a weight loss mark that exceeds Eli Lilly's oral GLP-1 drug Orforglipron, and an oral version of Novo Nordisk's high-dose GLP-1 peptide drug Semaglutide. Earlier this month, Eli Lilly reported on Orforglipron's Phase 3 data, disappointing analysts with measures of weight loss and tolerance, leaving the door open to smaller competitors (such as Viking).
Thomas Smith, an analyst at Leerink Partners, said in a study that the weight loss achieved by Viking's Pill is competitive with Lilly's Orforglipron, but the difference in titration of drugs in their respective studies makes cross-trial comparisons difficult. In the Phase 2 test of Eli Lilly drug, titration varies as patients with high-dose arm reach dose at week 12. In contrast, patients receiving high doses of Viking reached this dose level by week 6. Viking Management said on Tuesday's call that the company plans to further titration, which Smith said will provide the potential to optimize efficacy and tolerance.
Both Hsieh and Smith sold Viking stocks into exaggeration. The tolerability curve for VK2735 was poor compared to Phase 1, but William Blair saw a placebo-like profile at the 30 mg dose. The company believes that this dose can be selected as a potential maintenance dose in key tests of the drug. Given the higher costs associated with producing higher doses, HSIEH believes that Vikings are unlikely to raise the two higher doses to critical tests. He added that tolerance can be reduced and improved by expanding the titration to four weeks in the shorter two weeks in the phase 2 trial, called Venture-Oral. HSIEH is seeking an upcoming Phase 2 overall protocol study that will explore the transition from injection of VK2735 to maintenance treatment with monthly injections or daily expression of Viking drugs.
“Given that people seeking chronic weight management treatments may be looking for rapid initial weight loss, we believe that subcutaneous injections will continue to be preferred during the initial treatment,” Hsieh said. “According to the venture capital study, there are good locations in a 30mg or 60mg maintenance environment, we think this represents the biggest [total addressable market] In the obesity market, chronic drivers of disease. ”
The market for potential oral obesity medications is competitive. In addition to Eli Lilly and Novo Nordisk, structural therapy is in mid-stage clinical development with oral small molecule agonists with GLP-1. Roche is in early clinical development with the oral GLP-1 drug codenamed CT-996 from its $2.7 billion Carmot Therapeiutics. Startups are also part of the portfolio. Response Pharmaceuticals recently reported phase 2 data for its two daily drug, which was performed after a novel target called IMTP.
Not all verbal efforts to obesity medication efforts have been successful. Earlier this year, Pfizer stopped working on oral small molecules targeting GLP-1 after hepatic complications in a phase 1 test.
Photo: Martin Barraud, Getty Images
