Recent early-stage clinical data on oral weight loss drug candidates have sparked interest in the competitive landscape of obesity treatments. However, the data released by three major players—Novo Nordisk, Roche, and Terns Pharmaceuticals—present a mix of promising results and critical questions that leave analysts cautious about drawing definitive conclusions.

At the European Association for the Study of Diabetes (EASD) annual meeting, all three companies shared their findings from four-week trials of their oral obesity candidates. The data revealed some early efficacy numbers, but analysts cautioned that the results are complicated by differences in trial design and other variables that make direct comparisons challenging.

Weight Loss Figures: Who Leads the Pack?

According to the data, the three drugs showed varying degrees of weight loss after four weeks of treatment:

• Roche’s CT-996 led the pack with a placebo-adjusted weight loss of 6.1%.
• Terns Pharmaceuticals’ TERN-601 followed closely with a 4.9% weight loss.
• Novo Nordisk’s amycretin showed a 4% weight loss.

These results placed Roche and Terns among the stronger contenders, with Roche’s candidate standing out for the greatest weight loss achieved. Other recent data from competitors, such as Viking Therapeutics’ VK2735 (3.2%), Eli Lilly’s orforglipron (3.9%), and Pfizer’s danuglipron (5.2%), further emphasized the competitive dynamics. However, this ranking is far from straightforward.

Analysts noted that it’s difficult to determine whether the differences in efficacy are due to the molecules themselves or to factors related to trial designs, such as dosing schedules or patient populations. As a result, there remains considerable uncertainty about how these drugs will perform in the real world.

Roche’s Bold Approach: Efficacy vs. Tolerability

Roche’s CT-996 delivered the most impressive weight loss figures, but the company’s approach to rapid dose titration—quickly increasing doses during the trial—raised red flags about tolerability. Analysts from Jefferies highlighted that while Roche’s drug appeared effective, the high rate of side effects, including nausea, diarrhea, and vomiting, was a significant concern. For instance, the study saw nausea in 83.3% of participants, with diarrhea and vomiting in 50% and 33.3%, respectively, even in the cohort that received slower dose increases.

Jefferies analysts argued that Roche’s aggressive dosing strategy might explain the efficacy but warned that the true competitive profile of CT-996 wouldn’t be clear until the company completes larger Phase II trials, where dosing regimens may be adjusted to improve tolerability without compromising efficacy.

Despite these concerns, Roche remains a strong contender in the obesity drug market, with BMO analysts noting that the company is still relevant, even if it is a step behind leaders like Novo Nordisk and Eli Lilly.

Novo Nordisk’s Amycretin: Promising but with Manufacturing Challenges

Novo Nordisk’s oral obesity candidate, amycretin, combines GLP-1 and amylin agonism, acting on glucose regulation and appetite through a novel dual mechanism. While the drug’s tolerability data was underwhelming, it wasn’t seen as a major downside compared to other oral GLP-1 treatments. Analysts from BMO emphasized the growing importance of amylin in the obesity space, as the combination offers benefits beyond those seen with traditional GLP-1 therapies.

However, a critical issue for Novo Nordisk is the potential manufacturing challenges posed by amycretin. Jefferies analysts pointed out that, due to the peptide-based nature of amycretin, scaling up production to meet market demand could be a challenge. With projections indicating that Novo would need over 30 tons of active pharmaceutical ingredient (API) annually to meet sales expectations, reformulation or improved bioavailability might be necessary to streamline production and reduce costs.

Terns Pharmaceuticals: Innovative but Still Uncertain

Terns Pharmaceuticals has taken a unique approach with its candidate, TERN-601, which focuses on maximizing the drug’s effective exposure by utilizing high plasma protein binding, low solubility, and high gut permeability. This formulation strategy is intended to mimic the behavior of a long-acting oral drug, potentially allowing for higher doses that maximize weight loss while minimizing side effects.

Jefferies analysts noted that this could make Terns’ drug stand out from other oral GLP-1 candidates, which typically require lower doses to avoid intolerable side effects. However, this approach isn’t without its challenges. For one, the need for patients to take multiple tablets in high doses could lead to variability in dosing, complicating treatment consistency.

Despite these hurdles, Terns’ novel approach has caught the attention of analysts, with some predicting that the company could find a sweet spot in future trials where tolerability matches or even surpasses that of competitors like Eli Lilly’s orforglipron.

Looking Ahead: Unanswered Questions and Future Potential

While the early-stage data on these oral obesity drugs provides some promising insights, it’s clear that much remains uncertain. Key questions about long-term efficacy, tolerability, and scalability still need to be answered in larger Phase II and Phase III trials.

• Efficacy Comparisons: While Roche’s CT-996 showed the highest weight loss in the four-week study, concerns about tolerability and dosing need to be addressed.
• Manufacturing Issues: Novo Nordisk’s amycretin may face challenges in scaling production, which could hinder its ability to meet peak sales expectations.
• Novel Mechanisms: Terns Pharmaceuticals’ innovative approach has captured attention, but its long-term success will depend on resolving issues with dosing variability and ensuring effective treatment in larger populations.

As these companies continue to advance their candidates through clinical trials, the race to develop an effective, well-tolerated, and scalable oral obesity drug is far from over. Analysts will be closely watching how these drugs perform in future trials to determine which companies will emerge as the leaders in the obesity treatment market.

For now, the competition remains wide open, with multiple contenders vying for a slice of the lucrative weight loss market.

 

 

Source: https://www.biospace.com/drug-development/obesity-pill-races-heats-up-as-novo-roche-and-terns-share-data