What were the primary and secondary endpoints in Memoblast clinical trials and were they met?

1. What the trials defined as the primary endpoint — straightforward company and regulator alignment

Mesoblast and regulatory correspondence clarify the planned Phase 3 primary outcome: pain reduction assessed at 12 months (with company materials framing the pivotal primary endpoint as a composite of at least 50% reduction in low back pain and a 15‑point improvement in ODI plus no additional interventions) — the company website and trial descriptions consistently present the 50% VAS pain reduction + 15‑point ODI + no intervention composite as the efficacy bar ^{[2] [3]}. OTAT/FDA feedback accepted pain reduction at 12 months as the primary endpoint for the next US trial, with functional improvement and opioid‑usage reduction designated as secondary endpoints in the program plan ^[1].

2. Secondary endpoints reported in company and public filings

Mesoblast’s program explicitly lists functional improvement (ODI change) and opioid use reduction as key secondary endpoints; ClinicalTrialsArena and a Mesoblast SEC filing note that quality of life, function and decline in opioid usage are among the principal secondary measures the company will evaluate in the Phase 3 program ^{[5] [1]}. Company web pages reiterate the combination of pain and function as primary focus while calling out opioid and QoL outcomes as supportive evidence ^{[2] [3]}.

3. What the trials actually achieved — trial readouts and peer‑reviewed analysis

The peer‑reviewed report on the 36‑month randomized study concluded that although all treatment groups showed substantial within‑group improvement from baseline in least‑squares mean low back pain and ODI, the primary efficacy endpoint did not reach statistical significance for either treatment group compared with control across all subjects; none of the secondary endpoints showed significant differences between treatment and control in the full study population ^[4]. Mesoblast’s corporate communications highlight durable reductions in back pain out to three years from a single injection, but the SEC filing and scientific report make clear that the controlled primary comparison in the completed trial failed to meet statistical significance in the full cohort ^{[1] [4]}.

4. Where interpretations diverge — company messaging vs. formal analysis

Mesoblast’s presentations emphasize durable pain reductions and subgroup signals (for example subjects with shorter pain duration) and argue these effects support further confirmatory trials ^{[1] [3]}. Independent reporting and the ScienceDirect article stress that the randomized trial did not achieve its primary endpoint in the overall trial population and that secondary endpoints likewise lacked significance — the peer‑reviewed conclusion recommends a targeted confirmatory trial focused on subjects with shorter LBP duration to corroborate apparent subgroup benefits ^[4].

5. Why the company is moving forward — regulatory reasoning and strategy

OTAT’s feedback to Mesoblast accepted pain reduction at 12 months as the appropriate primary endpoint for a new Phase 3 registration trial and agreed that functional improvement and opioid reduction can serve as secondary endpoints, effectively green‑lighting a redesigned confirmatory trial after review of the completed data ^[1]. That regulatory acceptance explains why Mesoblast has initiated another pivotal study with a 12‑month pain primary endpoint and predefined secondary measures ^{[5] [1]}.

6. Limitations, open questions and the evidence gap

Available sources show clear disagreement between company emphasis on long‑term, within‑group benefits and the formal randomized analysis that the primary endpoint was not met in the full cohort; sources do not provide patient‑level subgroup p‑values here beyond suggesting benefit in subjects with LBP <68 months, so the strength of those subgroup claims is not fully documented in the materials provided ^{[4] [1]}. Available sources do not mention whether the company adjusted statistical hierarchy or multiplicity plans for opioid endpoints in the new trial beyond noting FDA interest in how opioid metrics will be handled ^{[6] [1]}.

7. Bottom line for clinicians, patients and investors

Regulators accepted a clear 12‑month pain reduction primary for the next confirmatory study and listed function and opioid reduction as key secondaries ^{[1] [5]}. The completed randomized program produced promising within‑patient improvements and long follow‑up but did not meet the prespecified primary efficacy comparison in the overall cohort and failed to show significant secondary differences versus control in the published analysis ^[4]. Readers should therefore treat Mesoblast’s durability claims alongside the peer‑reviewed finding that the controlled primary endpoint was not achieved and watch the new, FDA‑agreed pivotal trial for a definitive regulatory‑grade result ^{[4] [1]}.