REC-4881 Shows Early Promise in FAP, But Questions Remain on Consistency and Safety

The preliminary results of Recursion Pharmaceuticals’ (NASDAQ: RXRX) REC-4881 in Familial Adenomatous Polyposis (FAP) trials have sparked cautious optimism in the rare disease space. The Phase 1b/2 TUPELO trial data, released March 17, 2025, highlights a median 43% reduction in polyp burden—a key efficacy milestone—while also underscoring challenges in safety and variability of response. For investors, the data presents a compelling narrative for a first-in-class therapy targeting an unmet medical need, but the path to commercial success hinges on resolving critical uncertainties.

Efficacy: A Glimmer of Breakthrough Potential

In the Phase 2 cohort (n=6), REC-4881 (4 mg once daily) reduced polyp burden by a median 43% at Week 13—a stark improvement over historical benchmarks of 20–30% reduction observed in six months with other investigational agents. Five of six patients saw reductions between 31% and 82%, but one patient’s polyp burden surged by 595%, complicating the narrative. The Spigelman stage, a measure of upper GI severity, improved in half the patients, though two cases worsened or stagnated.

The data’s most striking feature is its speed: a 43% reduction in just three months compared to historical six-month metrics. Dr. Jewel Samadder of the Mayo Clinic called this “highly encouraging,” noting that FAP patients currently lack FDA-approved therapies. With an estimated 50,000 affected individuals in the U.S. and EU5, REC-4881’s potential market is both niche and high-value.

Safety: Balancing Risks with Class Effects

The safety profile raises red flags, particularly given MEK inhibitors’ known cardiac and metabolic risks. Among 19 patients in Phase 1b/2, 79% experienced Grade 1 or 2 treatment-related adverse events (TRAEs), including acneiform rash, diarrhea, and decreased left ventricular ejection fraction (LVEF). Three patients had Grade 3 TRAEs (e.g., rash, elevated CRP), and three discontinued treatment due to side effects.

Recursion’s decision to limit enrollment to patients aged ≥55—a cohort less prone to severe TRAEs—suggests a strategy to mitigate risks. However, the exclusion of younger patients raises questions about the drug’s broader applicability, as FAP often manifests in adolescents. The need for cardiac monitoring and dose adjustments adds layers of complexity for future trials and potential regulatory submissions.

Regulatory and Commercial Context

REC-4881 has secured Fast Track and Orphan Drug designations in the U.S., and Orphan status in the EU, accelerating its path to market. If approved, it could command premium pricing for rare disease therapies, potentially reaching $100,000–$200,000 annually per patient. However, the small trial size (n=6 efficacy evaluable) and outlier responses pose hurdles.

The 8 mg cohort’s exclusion of three patients due to “zero baseline polyp burden” further complicates the dose-response analysis, leaving efficacy questions unresolved. Recursion’s AI-driven TechBio platform, which identified REC-4881 by analyzing APC gene loss models, offers a unique selling point but cannot yet compensate for the data’s limitations.

Conclusion: A Promising Start, but Execution Remains Key

REC-4881’s preliminary efficacy—particularly its rapid polyp burden reduction—positions it as a potential first-in-class therapy for FAP. With no approved treatments, the market is wide open, and Recursion’s regulatory tailwinds could fast-track approval. However, the trial’s small size, inconsistent responses (including the 595% outlier), and safety concerns demand rigorous validation in larger Phase 2/3 trials.

Investors should weigh the 43% reduction against the risks: the stock’s price (currently around $15/share) reflects high expectations, but execution in late-stage trials and safety monitoring will be critical. If Recursion can replicate these results in a broader cohort while managing adverse events, REC-4881 could transform FAP care—and deliver significant returns. For now, the data is a step forward, but the finish line remains distant.

The journey ahead is fraught with uncertainty, but for a company built on AI-driven drug discovery, this trial is a proof point of Recursion’s ability to tackle rare diseases. The next 12 months—when additional TUPELO data is expected—will be pivotal in determining whether REC-4881 can live up to its early promise.