Viking Therapeutics' Oral Obesity Drug Shows Promise, but Faces Challenges

Viking Therapeutics has reported promising phase 2 data for its oral obesity drug candidate, VK2735, demonstrating significant weight loss potential. However, the results have been met with mixed reactions from investors due to concerns about tolerability and commercial viability.

Efficacy and Weight Loss Results

The phase 2 study, which included 280 adults, compared multiple doses of VK2735 to placebo over a 13-week period. Key findings include:

• Placebo group: 1.3% weight loss
• VK2735 treatment groups: Weight loss ranging from 2.3% to 12.2%
• Highest efficacy: 12.2% weight loss at the top dose after 13 weeks

Viking CEO Brian Lian, Ph.D., noted that patients experienced further weight loss at 16 weeks, suggesting the potential for greater reductions in longer trials. These results position VK2735 competitively against other obesity treatments in development, such as Novo Nordisk's oral semaglutide (15.1% weight loss after 68 weeks) and Eli Lilly's candidate (12.4% weight loss after 72 weeks).

Tolerability Concerns and Discontinuation Rates

Despite the promising efficacy data, the study revealed significant tolerability issues, particularly at higher doses:

• Discontinuation rates were dose-dependent, ranging from 20% at lower doses to 38% at the top dose
• Nausea was the primary reason for treatment discontinuation
• At the highest dose, rates of nausea were:
  • Mild: 38%
  • Moderate: 18%
  • Severe: 5%
• Vomiting occurred in 35% of patients at the top dose

Dr. Lian suggested that slowing the rate of dose titration could potentially improve the tolerability of VK2735. The company is also exploring alternative dosing strategies, such as titrating up to a high dose and then dropping down to a lower maintenance dose, which showed continued weight loss increase to 9.2% by Week 13 in an exploratory cohort.

Commercial Viability and Future Development

The study results have raised questions about which doses of VK2735 are commercially viable, considering the amount of peptide they contain. Viking's CEO asserted that the 30 mg dose "is absolutely commercially viable," and higher doses may also be feasible. However, the company faces competition from Novo Nordisk, which is seeking approval for a 25-mg dose of its oral semaglutide, and Eli Lilly, which is developing a small molecule that could be cheaper and easier to manufacture than peptides.

Viking has not yet identified which doses will be advanced to further trials, with Dr. Lian stating that it's premature to make such decisions until they have the full complement of data. The company is considering various approaches to balance efficacy, tolerability, and commercial viability, including the potential for low-dose maintenance therapy to retain and extend weight loss.

Despite the promising aspects of the VK2735 data, investor reaction has been cautious. Viking Therapeutics' stock fell 37% to $26.36 in premarket trading following the announcement, reflecting concerns about the drug's competitive position against more advanced assets from Lilly and Novo Nordisk.