Lantheus Holdings, Inc. and POINT Biopharma Global Inc. announced statistically significant topline results from the pivotal Phase 3 SPLASH study evaluating the efficacy and safety of 177Lu-PNT2002, a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), in patients with metastatic castration-resistant prostate cancer (mCRPC) after progression on an androgen receptor pathway inhibitors (ARPI). The SPLASH trial met its primary endpoint, demonstrating a median radiographic progression-free survival (rPFS) per blinded independent central review of 9.5 months for patients treated with ARPI in the control arm, a statistically significant 29% reduction in the risk of radiographic progression or death (hazard ratio [HR] 0.71; p=0.0088). At the time of the analysis, interim overall survival (OS) results were immature (46% of protocol-specified target OS events reached), the HR was 1.11.

The companies expect additional, follow-up data in 2024 prior to the potential submission of a New Drug Application (NDA). 177Lu-PNT2002 demonstrated a favorable safety profile with grade 3 treatment-emergent adverse events (TEAEs) per Common Terminology Criteria for Adverse Events (CTCAE), serious TEAEs, and TEAEs leading to discontinuation occurring at lower rates in the 177Lu-PNT2002 arm than in the ARPI arm (30.1%, 17.1%, and 1.9% vs. 36.9%, 23.1%, and 6.2%, respectively).

The open-label study randomized 412 patients with PSMA-expressing mCRPC who had progressed on ARPI therapy and either declined or were not eligible for chemotherapy, in a 2:1 randomization ratio (177Lu-PNT2002: control group). About 177Lu-PNT2002 is a PSMA-targeted, lutetium 177-based radioligand therapy candidate that combines a PSMA-targeted ligand, PSMA-I&T, with the beta-emitting radioisotope no-carrier-added lutetium-177. Lantheus Holdings, Inc., in-licensed exclusive worldwide commercialization rights (excluding certain Asian territories) to 177Lu-PNT2002 from POINT in December of 2022.

In April of 2023, the FDA granted Fast Track designation for 177Lu-PNT2002 for the treatment of mCRPC. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and address unmet medical needs. Such forward-looking statements are based upon current plans, estimates and expectations that are subject to risks and uncertainties that could cause actual results to materially differ from those described in the forward-looking statements include (i) the outcome of the SPLASH trial after full data is available; (ii) a delay in obtaining, or failure to obtain, a positive positive positive results in the SPLASH trial.