Mesoblast’s first randomized Phase 3 trial in chronic discogenic low back pain reported a more than three-fold increase in opioid cessation at 36 months for patients receiving a single intradiscal injection of rexlemestrocel-L plus hyaluronic acid versus saline (p=0.008) among the 168 baseline opioid users in the 404-patient study. FDA feedback from a recent Type B meeting acknowledged that effects on pain intensity favored the active arm and indicated that a clinically meaningful pain reduction at 12 months can support efficacy for a Biologics License Application. The agency also indicated that robust, well-controlled data on opioid reduction could be included in the Clinical Studies section of labeling.
The core development is FDA’s guidance to Mesoblast on a potential BLA for rexlemestrocel-L in chronic low back pain due to inflammatory degenerative disc disease, with 12-month pain reduction as the approvable endpoint. A confirmatory, 300-patient, randomized, placebo-controlled Phase 3 trial (MSB-DR004) using that endpoint is over 50% enrolled across 40 U.S. sites and is expected to complete enrollment within three months. The program holds RMAT designation, enabling rolling review and eligibility for priority review at filing. Secondary endpoints emphasize function and quality of life, and the trial is intentionally enriched for patients with disease duration under five years and includes those using opioids.
Strategically, Mesoblast is leaning into FDA’s 2025 draft guidance on non-opioid analgesics by pairing a conventional pain endpoint with long-horizon opioid-sparing data. Positioning opioid cessation in labeling—even within the Clinical Studies section rather than as an indication—could be commercially meaningful in a category where payer scrutiny is intense and prescriber behavior is increasingly shaped by opioid stewardship. The company is also narrowing biological and procedural variability by focusing on inflammatory DDD, employing an HA delivery vehicle, and standardizing a single intradiscal administration. The tension remains the field’s historical placebo sensitivity and heterogeneity of CLBP phenotypes, which demand tight site controls and consistent patient selection to replicate prior signals.
For sites, the program favors interventional capabilities and radiologic rigor, with implications for staffing, training, imaging criteria, and sterility procedures to mitigate injection-related risks. Longitudinal follow-up to 12 months for the primary and beyond for opioid outcomes will require robust retention infrastructure, ePRO/eCOA systems tuned to pain intensity, and objective capture of opioid use—ideally via EHR and PDMP data integration rather than self-report alone. CROs and vendors supporting this trial will need to harmonize procedural SOPs across 40 centers, manage cold-chain logistics for an allogeneic, cryopreserved product, and ensure consistent opioid tapering protocols to reduce confounding. For regulators and payers, the emerging template—pain reduction as approvable with opioid reduction included in labeling—could influence future chronic pain development programs and coverage frameworks.
The near-term watch items are completion of MSB-DR004 enrollment and any clarity on timing for a rolling BLA. The pivotal question is reproducibility of a clinically meaningful 12-month pain reduction alongside consistent functional gains, with acceptable procedure-related safety across a broader site network. Investigators and sponsors should watch how opioid cessation is operationalized in MSB-DR004—standardized taper plans, verification methods, and handling of rescue medications will shape interpretability and labeling relevance. Manufacturing scale-up and lot-to-lot consistency will come under increased scrutiny if the program advances to review. Ultimately, the FDA’s openness to embedding opioid-use outcomes in labeling sets a precedent; whether rexlemestrocel-L can deliver a durable, regulator-ready signal across pain, function, and opioid reduction will determine how far that precedent carries into practice.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
