Viking Therapeutics’ dual-targeting oral weight loss drug has disappointed investors after it showed lower efficacy than offerings from pharma giants Novo Nordisk and Eli Lilly.
Though VK2735, a glucagon-like receptor 1 and glucose-dependent insulinotropic polypeptide agonist (GLP-1/GIP-RA), met its primary endpoint – triggering a statistically significant weight loss of up to 12.2% from baseline during the Phase II VENTURE-Oral Dosing trial (NCT06068946). However, this number was lower than both Lilly’s orforglipron or Nordisk’s oral Wegovy (semaglutide) in terms of efficacy. The trial investigated five doses of Viking’s drug, ranging from 15mg to 120mg.
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Investors are unhappy with the results, as Viking’s stock value dropped by 42% from $42.09 at market close on 18 August to $25.99 at market open on 19 August following the debut of the Phase II results.
One of the main causes of concern for investors were adverse events (AEs), with 38% of patients in the 120mg group, where the 12.2% weight loss was seen, discontinuing treatment – signalling that lower doses will likely be needed to ensure tolerability. Most AEs were gastrointestinal (GI).
In response to this, Viking’s CEO Brian Lian assured investors that “GI adverse events tended to happen early,” and that they “resolve fairly rapidly with continued dosing”.
Lian also expressed excitement over the results, noting that the “progressive nature” of the weight loss curves observed could tout VK2735’s potential to increase weight loss during longer dosing periods.
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By GlobalDataThe company will also explore VK2735’s use as a maintenance therapy moving forward, as an exploratory assessment found that a 30mg maintenance dose following a 90mg daily regimen could prevent weight regain.
Novo Nordisk remains ahead
Viking’s top-line efficacy data will be welcome news for Danish pharma Novo Nordisk, as its oral version of Wegovy will remain top of the charts in terms of efficacy in the obesity pill niche – triggering weight loss of 13.6% after 64 weeks in the OASIS4 trial (NCT05035095).
Novo Nordisk is currently awaiting the US Food and Drug Administration’s (FDA) decision on oral Wegovy in obesity, with the regulator expecting to announce its verdict by Q4 of 2025. If approved, analysts at Pharmaceutical Technology’s parent company, GlobalData, forecast that the drug will make $5.2bn in 2031.
However, Eli Lilly could be poised to snatch some of Novo Nordisk’s market share if its oral candidate, orforglipron, was to receive approval – though Phase III data puts the drug just behind Rybelsus in terms of efficacy in obesity. Lilly plans to file for regulatory review by the end of 2025.
Though obesity pills from Viking, Novo Nordisk and Lilly have all shown promise in the obesity category, Costanza Alciati, Pharma Analyst for GlobalData, stated that at present a pill is “unlikely to be able to surpass the efficacy of injectable formats like Wegovy and Zepbound in terms of weight loss”, though companies should aim to achieve comparable efficacy.
Aliciati also noted that the future obesity pill market will look a little different to its injectable counterpart – likely attracting patients who are resistant to injectable GLP-1RA treatments.
“This makes it hard to know how the introduction of GLP-1RA pills will impact injectable sales, as the pill offers other benefits like patient-centric administration, easier storage and potential lower costs,” Aliciati said.
Though there are many unknowns in this prospective market, Aliciati believes that there is “still promise in Viking’s candidate”, as efficacy has been proven and no drug has yet reached the oral GLP-1RA obesity market.
“Prior to the Phase III ATTAIN-1 readout, we believe the consensus view positioned orforglipron as the de facto maintenance option for patients aiming to curtail weight rebound following achievement of their weight loss goal,” said William Blair analyst Andy Hsieh in a research note.
“However, given the underwhelming weight loss magnitude, coupled with potential uncertainties associated with the persistent rate of adverse events (as observed in the Phase III ACHIEVE-1 study in type 2 diabetes), we believe the setback creates a clinical void for smaller competitors, such as Viking, to fill.
“Overall, we continue to believe that Viking’s obesity franchise offers a unique set of attractive qualities that will be viewed favorably through the lens of big pharma from an M&A perspective,” Hsieh added.
