Agreement reached for public reimbursement of Pluvicto in Canada

Novartis has successfully completed an agreement with the pan-Canadian Pharmaceutical Alliance (pCPA) to secure public reimbursement of lutetium (¹⁷⁷Lu) vipivotide tetraxetan injection (Pluvicto; formerly ¹⁷⁷Lu-PSMA-617) for patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) across Canada.¹

Earlier this year, Novartis completed an FDA submission for an expanded label of Pluvicto in the US.

“This outcome is very good news for patients and their families,” said Ricardo Rendon, MD, FRCSC, President of the Canadian Urological Association, in the news release.¹ “Over the years, I have treated many patients who have exhausted all treatments, facing devastating challenges. This development offers hope, bringing us closer to providing patients with advanced prostate cancer public access to a therapy they have long awaited.”

However, the process is not yet fully complete, as Pluvicto still needs to be added to each province and territory’s formularies before patients can access the therapy.

On this, Novartis commented, “We look forward to timely collaboration with participating jurisdictions to ensure that eligible prostate cancer patients that are urgently awaiting treatment will have access without further delay.”

Additional news on Pluvicto

Pluvicto was approved by Health Canada in August 2022, making it the first targeted radioligand therapy approved in Canada for patients with mCRPC. The therapy is indicated for adult patients with PSMA-positive mCRPC who have received at least 1 androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy.

The therapy was also approved by the US FDA in March 2022 under the same indication.² Earlier this year, Novartis completed an FDA submission for an expanded label of Pluvicto to include patients with mCRPC in the pre-taxane-based chemotherapy setting.³

This announcement was made in response to additional positive data from the phase 3 PSMAfore trial (NCT04689828), which showed that “Updated overall survival (OS) results from a pre-planned analysis at approximately 75% information fraction demonstrates an OS hazard ratio less than 1.0 (HR<1.0) in the intent-to-treat (ITT) population unadjusted for cross-over.”⁴

At the time of initial data report from PSMAfore in 2023, the unadjusted ITT OS analysis was confounded, with 84% of patients who discontinued treatment with ARPI due to radiographic progression crossing over to receive Pluvicto.⁵ The pre-specified crossover-adjusted OS analysis showed a HR of 0.80 (95% CI, 0.48-1.33).

In the updated data report, Novartis noted that radiographic progression-free survival (rPFS) and other key secondary end points were consistent with data reported in 2023, as well as the safety profile for Pluvicto, which included an additional 8 months of follow-up.

In October 2023, Novartis published data from the PSMAfore trial showing superior rPFS with Pluctivo compared with an ARPI in patients with PSMA-positive mCRPC who had progressed on a previous ARPI and had not received treatment with taxane-based regimen.⁵ Overall, the trial met its primary end point by showing that Pluvicto more than doubled the median rPFS to 12.0 months, compared to 5.6 months among patients who received a change in ARPI (HR, 0.43; 95% CI, 0.33-0.54; P < .0001).

Data also showed that a PSA decline of at least 50% was more than 2.5 times more frequent with Pluvicto than with a change in ARPI. Specifically, a PSA decline greater than 50% was observed in 57.6% of patients who received Pluvicto, vs 20.4% of patients who received a change in ARPI.

Additionally, patients who received Pluvicto demonstrated improved quality of life, with their FACT-P total score maintained for 7.5 months vs 4.3 months among those with a change in ARPI. Further, the delay in worsening pain score was maintained with Pluvicto for 5.0 months vs 3.7 months with a change in ARPI.

Grade 3 to 4 adverse events (AEs) were reported in 33.9% of patients who received Pluvicto and 43.1% of patients who received a change in ARPI. Serious AEs were observed among 20.3% and 28.0% of patients, respectively. AEs leading to a dose adjustment were experienced by 3.5% of patients in the Pluvicto cohort and 15.1% of patients in the change in ARPI cohort, and AEs leading to treatment discontinuation occurred in 5.7% and 5.2% of patients, respectively.

AEs among those who received Pluvicto were primarily grade 1 and 2 and included dry mouth (57.3%), asthenia (31.7%), nausea (31.3%), anemia (24.2%) and fatigue (22.9%).

In total, the open-label PSMAfore study included 469 patients with PSMA-positive mCRPC who had not received treatment with a taxane-based regimen. Those included in the study had tumors that had previously progressed on a second-generation ARPI consisting of either abiraterone, enzalutamide, darolutamide, or apalutamide.

Patients were randomly assigned 1:1 to receive Pluvicto or a change in ARPI. Those in the change in ARPI cohort were able to cross over to receive Pluvicto after experiencing radiographic progression as confirmed by blinded independent central review.

The study remains ongoing, with anticipated completion in September 2025.⁶

References

1. Novartis and the pan-Canadian Pharmaceutical Alliance achieve milestone agreement for PLUVICTO. News release. Novartis Pharmaceuticals Canada Inc. December 13, 2024. Accessed December 17, 2024. https://www.biospace.com/press-releases/novartis-and-the-pan-canadian-pharmaceutical-alliance-achieve-milestone-agreement-for-pluvicto

2. Novartis Pluvicto approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. News release. Novartis. March 23, 2022. Accessed December 17, 2024. https://www.novartis.com/news/media-releases/novartis-pluvictotm-approved-fda-first-targeted-radioligand-therapy-treatment-progressive-psma-positive-metastatic-castration-resistant-prostate-cancer

3. Novartis continues strong momentum in Q3 with 10% sales growth, 20% core operating income growth, and important innovation milestones; raises FY 2024 guidance. News release. Novartis. October 29, 2024. Accessed December 17, 2024. https://www.novartis.com/news/media-releases/novartis-continues-strong-momentum-q3-10-sales-growth-20-core-operating-income-growth-and-important-innovation-milestones-raises-fy-2024-guidance

4. Novartis confirms plans to file for Pluvicto pre-taxane label expansion in H2 2024 based on latest data from Phase III PSMAfore study. News release. Novartis. April 4, 2024. Accessed December 17, 2024. https://www.novartis.com/news/novartis-confirms-plans-file-pluvicto-pre-taxane-label-expansion-h2-2024-based-latest-data-from-phase-iii-psmafore-study

5. Novartis Pluvicto shows clinically meaningful and highly statistically significant rPFS benefit in patients with PSMA-positive metastatic castration-resistant prostate cancer in the pre-taxane setting. News release. October 23, 2023. Accessed December 17, 2024. https://www.novartis.com/news/media-releases/novartis-pluvictotm-shows-clinically-meaningful-and-highly-statistically-significant-rpfs-benefit-patients-psma-positive-metastatic-castration-resistant-prostate-cancer-pre-taxane-setting

6. 177Lu-PSMA-617 vs. androgen receptor-directed therapy in the treatment of progressive metastatic castrate resistant prostate cancer (PSMAfore). ClinicalTrials.gov. Last updated August 27, 2024. Accessed December 17, 2024. https://clinicaltrials.gov/study/NCT04689828