Ironwood Phase 3 results

March 1, 2024

This is not investment advice. We used AI and automated software tools for most of this research. A human formatted the charts based on data / analysis from the software, prompted the AI to do some editing, and did some light manual editing. We did some fact checking but cannot guarantee the accuracy of everything in the article. We do not have a position in or a relationship with the company.

Ironwood Pharmaceuticals recently announced the successful results of their global Phase III STARS trial, focusing on the efficacy and safety of apraglutide in treating adults with Short Bowel Syndrome with Intestinal Failure (SBS-IF). SBS-IF is a challenging condition where patients are significantly dependent on parenteral support (PS) due to their inability to absorb nutrients effectively through their intestines. The condition affects approximately 18,000 adults across the U.S., Europe, and Japan.

The trial, which was a multicenter, double-blind, randomized, and placebo-controlled study, tested the impact of once-weekly subcutaneous injections of apraglutide on reducing PS dependency. It was reported that apraglutide met its primary endpoint, showing a significant relative change from baseline in actual weekly PS volume at week 24. Specifically, the change for apraglutide versus placebo was -25.5% vs. -12.5%, with a p-value of 0.001, indicating a substantial reduction in PS dependency among participants treated with apraglutide.

Furthermore, apraglutide demonstrated clinically meaningful improvements, with a notable percentage of patients achieving at least one day off PS per week at the 24-week mark. This outcome underscores the potential for apraglutide to reduce the treatment burden on patients, enhancing their quality of life.

• The trial also explored several key secondary endpoints, where apraglutide showed statistical significance in the first two, related to patients achieving at least one day off PS per week and improvement in weekly PS volume in the stoma population.
• However, in the colon-in-continuity patients, while apraglutide was numerically favorable, it did not reach statistical significance for the latter secondary endpoints focused on days off PS and reaching enteral autonomy at week 48.

Safety-wise, apraglutide was well-tolerated, with a safety profile consistent with previous studies. This aspect is crucial, as it indicates that the treatment's benefits do not come at the expense of significant adverse effects.

Given these positive outcomes, Ironwood plans to submit a New Drug Application (NDA) and other regulatory filings for apraglutide as a once-weekly GLP-2 analog for adult patients with SBS dependent on PS. The trial's success marks a significant advancement in the potential treatment options for SBS-IF, offering hope for improved management of this severe condition. Ironwood's commitment to presenting further data at upcoming medical conferences and working with regulators to make apraglutide available highlights the potential impact of this treatment on the standard of care for SBS-IF patients.

Market opportunity

The market opportunity for apraglutide presents a complex scenario that warrants a rigorous and objective analysis. Ironwood Pharmaceuticals' investment in apraglutide, a long-acting GLP-2 analog intended for the treatment of Short Bowel Syndrome with Intestinal Failure (SBS-IF), is significant, underlined by a $1 billion acquisition and subsequent Phase 3 clinical trial. However, the immediate market reaction to the Phase 3 results reflects investor skepticism regarding apraglutide's competitive market position. Here are the critical points to consider:

• Clinical Efficacy Compared to Competitors
  • Apraglutide vs. Gattex (Teduglutide): The Phase 3 STARS trial showed apraglutide led to a 25.5% reduction in parenteral support (PS) volume, compared to a 12.5% reduction with placebo. In contrast, Takeda's Gattex, a daily GLP-2 analog, showed a more tangible outcome with a 4.4-liter decline in PS from a baseline of 12.9 liters over 24 weeks. Given the limitations of cross-trial comparisons, these results do not definitively position apraglutide as superior to Gattex in terms of reducing PS volume.
  • Apraglutide vs. Glepaglutide: Zealand Pharma's glepaglutide, another long-acting GLP-2 analog with twice-weekly dosing, reported a 5.13-liter drop in PS volume in its trial. Although the baseline for this reduction was not disclosed, the absolute reduction figure poses a competitive challenge to apraglutide, particularly if glepaglutide's baseline is comparable to Gattex's.
• Market Dynamics and Unmet Needs

  The SBS-IF market is niche, with an estimated 18,000 patients globally. Despite its size, the market is characterized by a high unmet need for treatments that can significantly reduce or eliminate the dependency on PS, thus improving patients' quality of life.

  Apraglutide's once-weekly dosing offers a potential advantage in terms of convenience over daily treatments like Gattex. However, the clinical benefit, as perceived through the reduction in PS volume and the drug's ability to meet secondary endpoints, especially in colon-in-continuity (CIC) patients, remains a concern. CIC patients represent a significant portion of the SBS-IF population, and apraglutide's failure to demonstrate efficacy in this subgroup could limit its market penetration.

• Commercial Prospects

  Ironwood's strategy to position apraglutide as a potentially best-in-class option hinges on its potency, selectivity, and dosing convenience. Yet, the market's initial reaction suggests skepticism about its ability to outcompete existing and forthcoming therapies, particularly considering the impending threat of generic versions of Gattex and the advancement of glepaglutide.

Conclusion

The market opportunity for apraglutide in SBS-IF is nuanced. While there is a clear unmet need for more convenient and effective treatments, apraglutide's market opportunity is clouded by competitive pressures and the mixed clinical results reported in the Phase 3 trial. The advantage of once-weekly dosing may appeal to a subset of patients and clinicians looking for less frequent dosing regimens. However, overcoming the skepticism reflected in the stock market's reaction and proving its value over competitors will require strategic pricing, effective marketing, and possibly further evidence of its benefits across a broader range of patient subgroups, including those with CIC.

In summary, while apraglutide presents a potential improvement in the treatment landscape for SBS-IF, its market opportunity appears challenging. Success will depend on Ironwood's ability to differentiate apraglutide from its competitors and to address the concerns raised by the Phase 3 trial outcomes.