In a Rare Disease Battleground, REC-4881 Shows the First Glimmer of Control
Recursion’s Early Trial Data Reveals Promising Efficacy in Familial Adenomatous Polyposis—But Challenges Loom in Turning a Niche Asset Into a Scalable Franchise
SAN DIEGO — Beneath the vaulted halls of the 2025 Digestive Disease Week conference, Recursion Pharmaceuticals took the stage to unveil data that could alter the course of a devastating hereditary cancer syndrome. REC-4881, an experimental MEK1/2 inhibitor developed through the company’s AI-driven Recursion OS platform, demonstrated a median 43% reduction in gastrointestinal polyp burden after just 13 weeks of treatment in patients with Familial Adenomatous Polyposis —a rare genetic disorder that, if left untreated, carries a near-certain risk of colorectal cancer.
For a disease with no FDA-approved pharmacologic treatments and where surgery is the only viable defense, the signal from REC-4881 represents more than just another clinical readout—it suggests the first steps toward therapeutic control in a condition long defined by inevitability.
A High-Stakes Trial in an Orphan Arena
FAP affects approximately 50,000 individuals in the U.S. and EU5. Caused by inherited mutations in the APC gene, patients often develop hundreds to thousands of polyps throughout the gastrointestinal tract. Despite advances in endoscopy and surgical prophylaxis, most face the prospect of multiple operations, impaired quality of life, and a lifetime tethered to surveillance.
Recursion’s TUPELO trial—a Phase 1b/2 study—seeks to change that paradigm. In its Phase 2 open-label cohort of post-colectomy patients aged 55 and older, five of six participants receiving 4 mg of REC-4881 daily saw reductions in polyp burden ranging from 31% to a striking 82%. At the 13-week evaluation point, three had also improved their Spigelman stage—a measure of disease severity in the upper GI tract—highlighting the compound’s potential beyond the colon.
“This is the first time we’ve seen a MEK inhibitor deliver such a rapid and deep signal in FAP,” noted one analyst attending the conference. “The biological rationale is strong—APC loss hyperactivates the MAPK pathway, and MEK1/2 sits right in the middle of that cascade. But translating that into real clinical effect in three months? That’s meaningful.”
An Early Win—But From a Small Hand
Still, caveats persist. The sample size remains modest—only six patients in the efficacy cohort at this stage. One outlier saw a 595% increase in polyp burden, suggesting potential heterogeneity in disease biology or drug response. In addition, while the 43% median reduction outpaces other treatments, it has yet to be tested against a placebo arm or over longer durations.
Comparison with historical benchmarks shows REC-4881 holds its ground, even in an unblinded study:
| Treatment | Median Polyp Reduction | Timeframe |
|---|---|---|
| REC-4881 (4 mg QD) | 43% | 13 weeks |
| Celecoxib (400 mg BID) | 30.7% | 6 months |
| Sulindac + Erlotinib | 37.9% | 6 months |
| eRapa (mTOR inhibitor) | 17% | 12 months |
These results place REC-4881 at the head of the pack in terms of early polyp regression, and perhaps more importantly, do so in a shorter treatment window. The implications for patient compliance and clinical trial design could be profound.
Safety Under the Microscope
While REC-4881’s efficacy drew attention, its safety profile will determine whether it becomes a true mainstay in FAP treatment. Across 19 patients evaluated across Phase 1b and 2, 79% experienced treatment-related adverse events , most of them Grade 1 or 2. However, 16% of patients developed Grade 3 side effects—including acneiform rash, elevated C-reactive protein, and decreased left ventricular ejection fraction .
No Grade 4 events have been reported so far, and dose modifications were infrequent. Still, experts are watching closely.
“MEK inhibitors carry a class risk,” said one clinical investigator involved in prior MEK-targeted studies. “Cardiovascular monitoring is essential, especially in older patients. The decision to limit Phase 2 enrollment to those over 55 years may help balance efficacy with tolerability, but this needs larger datasets.”
Notably, similar adverse effects have been reported with other MEK inhibitors like cobimetinib, where rash and diarrhea often define dose-limiting toxicity. In the TUPELO study, three patients discontinued treatment due to TRAEs, underscoring the need for vigilant long-term monitoring.
A Market Ripe but Limited by Numbers
Despite its rarity, FAP represents a high-value opportunity due to its intense clinical burden and orphan designation advantages. Market research estimates suggest the FAP treatment space could grow from $1.6 billion in 2022 to $4.85 billion by 2030, driven by prophylactic interventions, surgeries, and emerging therapeutics.
Assuming a conservative 25% penetration rate and net pricing of $150,000 per year—a common figure in orphan oncology—a viable REC-4881 franchise could exceed $600 million in peak annual revenue across the U.S. and EU5.
Importantly, the allosteric nature of REC-4881 may distinguish it from ATP-competitive MEK inhibitors, which have historically struggled with tolerability. Small molecule status also ensures low production costs and oral once-daily dosing, improving both margins and patient compliance.
Beyond the Clinic: Platform and Pipeline Implications
REC-4881 is more than a single-asset story. It is the first molecule to emerge from Recursion’s AI-guided discovery platform with Phase 2 data. The company’s partnership with NVIDIA to build large-scale biological foundation models—combined with earlier collaborations with Roche—suggests ambitions well beyond FAP.
“Even if REC-4881 stalls, Recursion’s platform has now proven it can take an asset from cellular imaging to clinical signal,” one investor remarked. “That’s a huge proof point for the model.”
Further, the APC gene is mutated in other tumor types, including subsets of colorectal and gastric cancers. If REC-4881 can suppress polyp formation through MEK inhibition in FAP, follow-on trials in sporadic adenomas or early-stage CRC prevention could open new indications.
Regulatory and Payer Terrain
With Orphan Drug and Fast Track designations secured in both the U.S. and Europe, REC-4881 is well-positioned to leverage accelerated pathways. Regulators have previously accepted endoscopic endpoints—like polyp burden and Spigelman staging—as surrogates in FAP trials, notably in the approval process for celecoxib.
Still, reimbursement may be complex. High drug costs and limited population size mean payers will demand robust data showing not just polyp reduction, but meaningful delays in colectomy or cancer progression. Modeling suggests cost-effectiveness will hinge on reducing the rate of surgical interventions and lifetime CRC incidence.
Next Milestones: Dose Escalation and Phase 3 Planning
Three patients have now been enrolled in an 8 mg QD cohort. However, none had measurable disease at baseline, making them inevaluable for efficacy at this stage. Future dosing arms will be closely scrutinized to determine whether higher concentrations lead to better durability—or unacceptable toxicity.
Key questions remain:
- Will REC-4881’s effects persist beyond treatment, or are polyps quick to rebound?
- Can long-term suppression prevent cancer, not just reduce burden?
- Will the FDA consider polyp metrics sufficient, or require histologic or survival endpoints?
Recursion has stated that updated efficacy and safety data from ongoing cohorts will be released in the second half of 2025. Phase 3 planning is already underway, and observers expect a randomized, placebo-controlled trial with at least 100 patients and endpoints tied to both upper and lower GI progression.
The Verdict: Cautious Optimism With Real Intrigue
REC-4881 has given Recursion its first tangible shot at a commercial product in a competitive, high-stakes space. Its efficacy is faster and deeper than any known competitor, its safety profile manageable so far, and its development story bolstered by AI-led discovery and regulatory tailwinds.
The challenge now is to sustain that momentum: expand the dataset, tighten the confidence intervals, and prepare for the rigorous demands of Phase 3. With a credible route to >$600 million in peak sales and minimal direct competition in FAP, the risk-reward calculus may increasingly favor bold investors and forward-looking clinicians alike.
“In a landscape dominated by surgery and surveillance, this could be the first true systemic option for FAP,” one researcher summarized. “It’s early, but it’s real.”
As the trial expands and new data arrives, the medical and investor communities will be watching closely—for both scientific validation and commercial traction. For now, REC-4881 stands as a rare beacon of possibility in a disease where patients have long had none.