ESMO: Lantheus' Phase 3 Radiotherapy Results Insufficient to Surpass Pluvicto, Analysts Say

Lantheus recently presented the latest data from its SPLASH study of Lu-PNT2002 at the European Society for Medical Oncology Congress (ESMO). This radioligand therapy targets prostate-specific membrane antigen (PSMA) and is being tested in patients with metastatic castration-resistant prostate cancer (mCRPC) who have already undergone treatment with an androgen receptor pathway inhibitor (ARPI). The 412-participant study revealed an overall response rate of 38.1% for Lu-PNT2002, compared to 12% for those who only received an ARPI. Previously, in December 2023, Lantheus reported that the study met its primary endpoint, showing a median radiographic progression-free survival (rPFS) of 9.5 months for Lu-PNT2002-treated patients, versus six months for those on an ARPI.

However, analysts at William Blair reviewed the ESMO data and expressed skepticism about Lu-PNT2002's market potential. They noted that the therapy's opportunities would be "significantly limited" to scenarios where Novartis's approved radiotherapy Pluvicto is unavailable. They referenced the phase 3 PSMAfore trial of Pluvicto, which demonstrated an objective response rate of 51%, higher than the 38% response rate for Lu-PNT2002 in the SPLASH study. Additionally, while overall survival rates have been debated in the investment community, the analysts pointed out an overall survival hazard ratio over the control arm of 1.11 for Lu-PNT2002, compared to 1.16 for Pluvicto.

The SPLASH trial administered Lu-PNT2002 at 6.8 GBq every eight weeks for up to four cycles. Despite reducing the maximum cumulative dose of Lu-PNT2002 to 27.2 GBq (versus 44.4 GBq for Pluvicto in the PSMAfore trial), the analysts remarked that this reduction did not result in better tolerability compared to Pluvicto. They concluded that Lu-PNT2002 is unlikely to disrupt the radioligand market due to its inferior clinical efficacy and comparable tolerability compared to Pluvicto. They speculated that Pluvicto would likely maintain market leadership in the post-novel hormone therapy mCRPC setting, following its anticipated approval based on positive phase 3 PSMAfore study results.

Despite this critical analysis, Oliver Sartor, M.D., Director of Radiopharmaceutical Trials and Professor of Medical Oncology at the Mayo Clinic in Rochester, Minnesota, expressed optimism about the SPLASH data. He noted that Lu-PNT2002 showed improvements in radiographic progression-free survival, positive interim crossover-adjusted overall survival hazard ratios, and enhanced quality of life. Sartor emphasized the significance of PSMA-targeted RLTs, including Lu-PNT2002, as viable treatment options for patients with limited choices after failing ARPI therapy.

Lantheus acquired Lu-PNT2002 from POINT Biopharma in 2022 for $260 million upfront. Jeff Humphrey, M.D., Lantheus's Chief Medical Officer, highlighted that the interim analysis demonstrated Lu-PNT2002's superior performance compared to the control arm and its potential to improve patients' quality of life.

In summary, while Lu-PNT2002 has shown promising results in certain areas, its future market impact may be constrained by competition from Pluvicto, which appears to offer superior efficacy and comparable tolerability. Nonetheless, the ongoing development and evaluation of PSMA-targeted therapies like Lu-PNT2002 continue to provide hope for mCRPC patients seeking new treatment options after ARPI therapy.