Today Viking Therapeutics reported results from its phase 2 study using its oral dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor drug VK2735 for the treatment of patients with obesity. It was revealed that the highest dose used in this mid-stage trial, 120 mg of VK2735, resulted in an average weight loss of up to 12.2% over a 13-week period from baseline. In terms of comparing this drug to a placebo, the proof-of-concept of this drug was shown. The reason why is because the patients who were given a placebo instead during the same period of time only achieved an average weight loss of 1.3%.
This was a highly extensive study because a total of 280 patients were recruited into this phase 2 VENTURE-Oral Dosing trial. Not only that, but the goal of the company was to test a variety of doses as well. There were 6 dosing arms of the oral VK2735 drug being tested compared to placebo. As I noted above, the highest dose of 120 mg is what achieved the best outcome in terms of percentage weight loss. However, it is key to note that the particular weight loss of 12.2% over the 13-week period is only when you are making a comparison to that of baseline. Meaning, the initial point when patients are first measured to the amount of weight loss achieved over an extended period of time.
Thus, when you are making the comparison of VK2735 on a placebo-adjusted basis, the percentage weight loss at the highest dose changes to 10.9%. The bottom line is that this drug was able to achieve statistical significance compared to placebo with all of the doses I noted above. In terms of safety, the drug fared pretty well, as treatment-emergent adverse events [TEAEs] of VK2735 were pretty much equal to that of placebo, with 90% and 85%, respectively. Therefore, this is definitely not what caused the stock price to crater as it did. What spooked investors was the reveal of how many patients discontinued treatment early. Roughly 38% of patients had to stop being treated with this GLP-1/GIP receptor drug because of adverse events.
The road for Viking Therapeutics is not completely closed, and there may be a path forward for it. The reason why is because in this main part of the study, there was the incorporation of an exploratory maintenance cohort. The significance of this is that it was a good move for management to include this since it may offer a path forward in a larger study to be tested. What this cohort entailed was the titration of 90 mg of VK2735 given daily. Patients took this amount of dosing for a total of four weeks and then were down-titrated to a lower dose of 30 mg daily. From there, this specific dosing was continued daily for a total of seven weeks. The purpose of this trial is to show that despite immediate weight loss being observed in these obesity patients, they can later on be moved to much lower dosing and still achieve a good amount of weight loss.
The point being that the company still has a path forward to test out the use of 90 mg of VK2735 and then down-titrate patients, possibly to a much lower dose below that of 30 mg. There might be two issues at play on why the stock price traded so much lower today. The first issue is the discontinuation of oral VK2735 because of adverse events. This is likely to be an issue because the company is trying to penetrate the large obesity space, which is highly crowded. Just a few weeks ago, Eli Lilly noted that patients taking its oral GLP-1 receptor agonist in the phase 3 ATTAIN-1 study achieved a weight loss of 12.4% at week 72. This is just an example and should be taken with a grain of salt.
That’s because, first and foremost, cross-trial comparisons are not ideal because there are many differentiating factors that go into running clinical studies. Not only that, but the trial that Eli Lilly ran was a longer 72-week study, compared to this study where Viking Therapeutics only treated patients for a 13-week period. Speaking of which, the company believes that with longer treatment, it might be possible for the patients being treated in the phase 2 VENTURE-Oral Dosing trial to achieve significantly more weight loss, although this remains to be seen. Novartis, though, might still have a slight edge, as its injectable semaglutide obesity drug can allow patients to achieve weight loss of 13.7%.
In terms of the science, it goes back to what I stated beforehand in that VK2735 is is a dual GLP-1/GIP receptor agonist. The dual component of it is believed to potentially allow for greater weight loss. The GLP-1 receptor is what is put in place to control blood sugar levels in a person and, of course, to suppress appetite. With a lower food intake, this is one component of allowing an obese person to lose weight. The other side, which involves the mechanism of action (MOA) of GIP agonism, also controls appetite. In essence, GIP receptor agonism is said to enhance that of the GLP-1 mode of action. The effect of such dual MOA has been proven with the FDA-approved weight loss drug Zepbound from Eli Lilly, which is a dual GLP-1/GIP receptor agonist.
The thing for Viking, though, is that its oral drug is quite behind, as the data just revealed only entails phase 2 clinical testing. It is going to need to see if it can perform well with oral VK2735 in a larger phase 3 study when given the green light to do so. Especially, it needs to establish further proof-of-concept that titrating down from 90 mg dosing to a much lower dose in terms of maintenance pays off.