Viking Therapeutics has reported phase 2 data on its oral obesity drug candidate, linking the peptide to weight loss of up to 12.2% after 13 weeks. But, with 38% of patients discontinuing treatment at the most effective dose, investors sent the stock down 37% in premarket trading.
The study compared multiple doses of an oral formulation of VK2735 to placebo in 280 adults. After 13 weeks of daily dosing, patients on placebo had lost 1.3% of their weight, while weight loss across the VK2735 arms ranged from 2.3% to 12.2%. Viking CEO Brian Lian, Ph.D., said on a call with investors that patients had further weight loss at 16 weeks, suggesting bigger reductions are possible in longer trials.
Further weight loss could take Viking up to and beyond the levels achieved by Novo Nordisk and Eli Lilly. Novo reported 15.1% weight loss after 68 weeks of treatment with oral semaglutide, although that trial used a higher dose than the one the pharma has submitted for approval. Lilly reported 12.4% weight loss after 72 weeks. Both sets of data disappointed investors, sending each respective pharma's stock sliding at the time.
However, there are questions about whether Viking can advance the most efficacious dose. The rate of discontinuations was dose dependent, rising from 20% at the bottom two doses to 38% at the top dose. Discontinuation of treatment was primarily driven by nausea. Lian said slowing the rate of dose titration could improve the tolerability of VK2735.
At the top dose, Viking reported rates of mild, moderate and severe nausea of 38%, 18% and 5%, respectively. The rate of vomiting was 35% on that dose.
Viking saw adverse events on placebo, too, with 40% of patients reporting mild nausea and 10% having vomiting. Lian said rates of nausea and vomiting on placebo in other recent trials have been higher than in the past, potentially because of expectations.
“Everybody knows somebody who's on a GLP-1 therapy and everybody knows the GI adverse events that are sort of expected from this mechanism,” Lian said. “That likely contributed to maybe a little bit of a sensitivity to people looking for it and it reported a little bit higher. I don't know, but there's nothing in the formulation that would have led to an elevated adverse event profile.”
Analysts have questioned which doses are commercially viable given the amount of peptide that they contain. Lian said 30 mg, the second from the bottom dose, “is absolutely commercially viable, and I think higher doses are also commercially viable.” Novo is seeking approval for a 25-mg dose. Meanwhile, Lilly is developing a small molecule that is cheaper and easier to manufacture than peptides.
The data raise questions about which doses Viking should advance. Lian declined to provide answers to analysts, telling people on the conference call that “it’s premature to identify the go-forward doses until we have the full complement of data.”
One possibility is that Viking manages the tolerability and commercial viability concerns by titrating up to a high dose and then dropping down to a lower maintenance dose. The company explored that approach in an exploratory cohort that received 90 mg before dropping down to 30 mg. Weight loss continued to increase on the lower dose, rising to 9.2% by Week 13.
“These results suggest that low-dose maintenance therapy may represent an effective means of retaining and potentially further extending weight loss that has already been achieved,” Lian said. “In addition, these data, along with the gradual weight loss observed in the 15 mg daily cohort, suggest that doses below 30 mg daily may also provide effective weight maintenance.”
Yet, investors have doubts about whether Viking can find a tolerability, efficacy and commercial viability profile that beats the more advanced assets in development at Lilly and Novo. Shares in the biotech fell 37% to $26.36 in premarket trading, sinking even further to $24.3 per share as of 12 p.m. ET.
Analysts with William Blair viewed the stock drop as "extreme and unwarranted," according to an Aug. 19 note.
"Overall, at the highest doses, oral VK2735 met the lofty goals of achieving 10%-11% weight loss on a placebo-adjusted basis at week 13," the analysts wrote, adding that the data "easily" outpace Lilly's candidate during the same timeframe, at 6% weight loss in a phase 2 study, and Novo's high-dose semaglutide, with 4% weight loss in a phase 3.
William Blair said it was "puzzled" by the fixation on the tolerability profiles of the higher doses, as it doesn't believe Viking will further the 90 mg or 120 mg daily regimen. The analyst said it expects Viking may move forward with the 30 mg dose as a potential maintenance dose for the pivotal study and noted that tolerability profiles can improve when the titration step-up is expanded to four weeks instead of two.
Editor's note: This article was updated at 12:15 p.m. ET to include analyst commentary.