The side effects make the oral obedience of Viking a difficult pill for investors to swallow

A Viking therapeutic drug which reaches two targets to arouse weight loss has achieved the objectives of a closely watched mid-term clinical trial, but with results that also show that many patients have stopped therapy due to gastrointestinal problems, which investors have considered the decline in prospects of the daily pill in an increasing field of oral medicine of obesity medicine.

The five doses of the drug, VK2735, led to statistically significant differences compared to the basic measures and the placebo in the study of 13 weeks of phase 2 of dose research, said Viking on Tuesday. The largest reduction in weight – an average of 12.2% – was observed in the highest dose, 120 mg. The preliminary results show reductions in body weight which were progressive at all doses throughout the study. This weight loss was not tackled from 13 weeks, which suggests that patients would continue to lose weight with longer dosage.

Viking has also reported that up to 97% of participants in the study’s medication weapons had allowed 5% or more weight loss, compared to only 10% of patients in the placebo group, a statistically significant result that achieves a secondary objective of the study. Up to 80% of patients who received VK2735 reached 10% or more weight loss, compared to 5% of those in the placebo group.

VK2735 is designed to target and activate two intestinal, GLP -1 and GIP receptors – the same targets struck by Eli Lilly’s blockbuster, an injectable medication once a week, Zepbound. Gastrointestinal problems, such as nausea and diarrhea, are a known side effect of metabolic drugs in this class of drugs. These side effects lead many patients to stop taking medication.

Viking develops injectable and oral subcutaneous formulations of VK2735. The oral version would offer a less heavy dosage option compared to weekly injections. Pills are also considered as potential maintenance treatment after patients have reached their target weight loss with an injectable obesity medication. But for any obesity pill to fulfill this role, an acceptable tolerability profile is essential.

In the Phase 2 test of the oral VK2735, the stop rates depended on the dose. The highest dose group had the highest stop rate with 38% of participants in this cohort stop treatment early compared to a stop rate of 18% in the placebo arm. Nausea was the most common unwanted event, reported in 58% of patients who received the study medication. This side effect was reported in 48% of those who received a placebo. Viking said most of the nausea were characterized as light or moderate. Vomiting was reported in 26% of patients who received VK2735, compared to 10% of those in the placebo group. The company said that gastrointestinal problems were generally observed at the start of treatment and decreased in frequency after repeated dosage.

The phase 2 study included an exploratory cohort designed to assess the VK2735 in weight loss maintenance. In this group, the participants were quickly titled at 90 mg of daily doses. After four weeks, patients received 30 mg of doses per day for seven weeks. Viking reported that this group showed rapid and gradual weight loss during the 90 mg treatment period. This weight loss was maintained after the transition to the lower daily dose.

Viking shares opened on Tuesday at $ 25.99 each, down more than 38% compared to the closing price on Monday. William Blair analyst Andy Hsieh recognized the problems of tolerability and higher stop rates that were worse than the encouraging data of phase 1 reported for the pill last year. But in a note sent to investors, Hsieh stressed that the weight loss lines displayed by VK2735 Ossu Ossin Phase 2 results for the Oral GLP-1 medication of Eli Lilly, Orforglipron, as well as the high dose of the oral version of Novo Nordisk of his semaglutide of drugs to Peptide GLP-1. Earlier this month, Eli Lilly reported phase 3 data for Orforglipron who disappointed analysts on weight loss and tolerability measures, leaving the door open to smaller suitors, such as Viking.

Leerink Partners’ analyst Thomas Smith said in a research note that the weight loss obtained by the Viking pill was competitive with Lilly Orforglipron, but the differences in the way the drugs have been titled in their respective studies make comparisons in quarter. In the phase 2 test of the drug Lilly, the titration varied with patients in the high dose arm reaching this dose by week 12. In comparison, patients who received the high dose of the Viking medication reached this dose level by week six. During a conference call on Tuesday, Viking Management said that the company provided more progressive titration in the future, which, according to Smith, will offer the potential to optimize efficiency and tolerability.

Hsieh and Smith consider that Viking’s actions sell as exaggerated. While the tolerability profile for VK2735 is worse in phase 2 compared to phase 1, William Blair sees the 30 mg dose with a placebo type profile. The company believes that this dose could be selected as a potential maintenance dose in the drug test test. Given the higher costs associated with the production of higher doses, Hsieh believes that it is unlikely that Viking will advance the two higher doses to pivotal tests. He added that tolerability can be attenuated and improved by widening the titration at four weeks in the study of phase 3 against two weeks in the shorter phase 2 trial, named Venture-Oral. Hsieh is considering a next 2 -2 master 2 -master protocol study which will explore the transition from VK2735 injectable to maintenance treatment with monthly injections or daily doses of the oral formulation of the Viking drug.

“Since people looking for treatment for chronic weight management probably seek a rapid degree of initial weight loss, we believe that subcutaneous injections will continue to be preferred during the initial treatment,” said Hsieh. “Based on the Venture-Ororal study, 30 mg or 60 mg are both well placed in the context of maintenance, which, in our view, represents the largest [total addressable market] in the obesity market driven by the chronicity of the condition. »»

The potential oral obesity drug market is competitive. In addition to the Eli Lilly and Novo Nordisk pills, therapeutics structure is in mid-term clinical development with an oral agonist with small GLP-1 molecules. Roche is at the start of clinical development with a CT-996 of the drug GLP-1 oral, which comes from its acquisition of $ 2.7 billion in Carmot Therapeutics. Startups are also part of the mixture. Pharmaceutical response has recently reported encouraging phase 2 data for its pill twice a day, which goes after a new target called IMTP.

All oral efforts have not succeeded. Earlier this year, Pfizer stopped work on a small oral molecule targeting GLP-1 after a liver complication emerged during phase 1 tests.

Photo: Martin Barraud, Getty Images