Positive survival data for Novartis investigational radioligand therapy 177Lu-PSMA-617 published in The New England Journal of Medicine

• VISION manuscript shows that ¹⁷⁷Lu-PSMA-617 plus standard of care (SOC) significantly improved overall survival and radiographic progression-free survival for patients with metastatic castration-resistant prostate cancer (mCRPC) compared to SOC alone¹

• US Food and Drug Administration (FDA) granted Breakthrough Therapy designation to ¹⁷⁷Lu-PSMA-617; regulatory submissions to US and EU Health Authorities on track for 2H21
  

• Novartis is a global leader in radioligand therapy, uniquely positioned with broad commercial experience, established manufacturing and supply chain capabilities, and extensive development expertise.

Basel, June 23, 2021 — VISION data published today in The New England Journal of Medicine (NEJM) shows that ¹⁷⁷Lu-PSMA-617 plus standard of care (SOC) significantly improved both overall survival (HR = 0.62 [95% CI: 0.52−0.74]; P<0.001; median 15.3 vs 11.3 months) and imaging-based progression-free survival (HR = 0.40 [99.2% CI: 0.29−0.57]; P<0.001; median, 8.7 vs 3.4 months) versus SOC alone in patients with progressive PSMA-positive mCRPC¹. VISION data were first presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting on June 6 (see media release).

“We are proud of these data showing that ¹⁷⁷Lu-PSMA-617 can significantly shrink tumors and extend life for patients with prostate cancer, who have been heavily pre-treated and currently have limited treatment options,” said Jeff Legos, Global Head of Oncology Development, Novartis. “We believe that radioligand therapy with ¹⁷⁷Lu-PSMA-617 has great potential to improve outcomes in advanced prostate cancer and have already started two new Phase III studies in earlier lines of treatment.”

Other data highlighted in the publication and ASCO presentation:

• Median time to first symptomatic skeletal event or death was 11.5 months in the ¹⁷⁷Lu-PSMA-617 plus SOC arm versus 6.8 months in the SOC only arm (P<0.001; α=0.05; HR = 0.50 [95% CI: 0.40, 0.62])¹
• Overall response rate in patients with measurable or non-measurable disease at baseline was 29.8% partial or complete response in the ¹⁷⁷Lu-PSMA-617 plus SOC arm compared to 1.7% partial response in the SOC only arm (two-sided p-value: <0.001)¹
• The incidence of grade ≥3 treatment-emergent adverse effects was 52.7% in the ¹⁷⁷Lu-PSMA-617 plus SOC arm vs 38.0% in the SOC only arm¹
• Serious drug-related treatment emergent adverse events occurred in 9.3% of patients in the ¹⁷⁷Lu-PSMA-617 plus SOC arm compared to 2.4% in the SOC only arm²

Two additional studies with ¹⁷⁷Lu-PSMA-617 radioligand therapy in earlier lines of treatment for metastatic prostate cancer are ongoing, investigating potential clinical utility in the mCRPC pre-taxane setting (PSMAfore) and in the metastatic hormone-sensitive setting (PSMAddition). Novartis is also evaluating opportunities to investigate ¹⁷⁷Lu-PSMA-617 radioligand therapy in earlier stages of prostate cancer.

The NEJM publication is available online at www.NEJM.org

About ¹⁷⁷Lu-PSMA-617
¹⁷⁷Lu-PSMA-617 is an investigational PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer. It is a type of precision cancer treatment combining a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle)^3-5. After administration into the bloodstream, ¹⁷⁷Lu-PSMA-617 binds to prostate cancer cells that express PSMA⁶, a transmembrane protein, with high tumor-to-normal tissue uptake^3,7,8. Once bound, emissions from the radioisotope damage tumor cells, disrupting their ability to replicate and/or triggering cell death^9-11. The radiation from the radioisotope works over very short distances to limit damage to surrounding cells^1,3,7.

About VISION
VISION is an international, prospective, randomized, open-label, multicenter, phase III study to assess the efficacy and safety of ¹⁷⁷Lu-PSMA-617 (7.4 GBq administered by intravenous infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen standard of care in the investigational arm, versus standard of care in the control arm¹. Patients with PSMA PET-scan positive mCRPC, and progression after prior taxane and androgen receptor pathway inhibitors, were randomized in a 2:1 ratio in favor of the investigational arm¹. The alternate primary endpoints were rPFS and OS¹. The study enrolled 831 patients¹.

Disclaimer
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About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 110,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

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References

1. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. New England Journal of Medicine 2021. doi: 10.1056/NEJMoa2107322
2. Morris M, et al. Phase 3 study of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). Oral presentation at: ASCO Annual Meeting; June 6, 2021
3. Kratochwil C, Giesel FL, Stefanova M, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with ¹⁷⁷Lu-labeled PSMA-617. J Nucl Med 2016;57(8):1170–6 [https://pubmed.ncbi.nlm.nih.gov/26985056/]
4. Eder M, Schäfer M, Bauder-Wüst U, et al. 68Ga-complex lipophilicity and the targeting property of a urea-based PSMA inhibitor for PET imaging. Bioconjug Chem 2012;23(4):688–97.
5. Benešová M, Schäfer M, Bauder-Wüst U, et al. Preclinical evaluation of a tailor-made DOTA-conjugated PSMA inhibitor with optimized linker moiety for imaging and endoradiotherapy of prostate cancer. J Nucl Med 2015;56(6):914–20
6. Haberkorn U, Eder M, Kopka K, et al. New Strategies in Prostate Cancer: Prostate-Specific Membrane Antigen (PSMA) Ligands for Diagnosis and Therapy. Clin Cancer Res 22(1):9-15.2016
7. Violet J, Jackson P, Ferdinandus J et al. Dosimetry of (177)Lu-PSMA-617 in metastatic castration-resistant prostate cancer: correlations between pretherapeutic imaging and whole-body tumor dosimetry with treatment outcomes. J Nucl Med 2019;60(4):517–23
8. Current K, Meyer C, Magyar CE et al. Investigating PSMA-targeted radioligand therapy efficacy as a function of cellular PSMA levels and intra-tumoral PSMA heterogeneity. Clin Cancer Res 2020;26(12):2946–55
9. Kassis A. Therapeutic Radionuclides: Biophysical and Radiobiologic Principles. Semin Nucl Med. 2008; 38(5): 358–366
10. Fendler W, Stuparu A, et al. Establishing 177Lu-PSMA-617 Radioligand Therapy in a Syngeneic Model of Murine Prostate Cancer. J Nucl Med 2017; 58: 1786–1792
11. Ruigrok E, van Vliet N, et al. Extensive preclinical evaluation of lutetium-177-labeled PSMA-specific tracers for prostate cancer radionuclide therapy. Eur J Nucl Med Mol Imaging. 2020; 48: 1339-1350

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