Novartis reports positive health-related quality of life data for 177Lu-PSMA-617 radioligand therapy in patients with advanced prostate cancer at ESMO 2021

New quality of life data for 177Lu-PSMA-617 plus standard of care shows delay in worsening of health-related quality of life (HRQoL) and pain in heavily pre-treated patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) compared to standard of care alone1 US Food and Drug Administration (FDA) granted Breakthrough Therapy designation to 177Lu-PSMA-617; Submission to FDA and European Medicines Agency on track for 2H21 Novartis committed to reimagining prostate cancer with targeted radioligand therapy; two Phase III studies with 177Lu-PSMA-617 in earlier lines of treatment ongoing with goal to investigate earlier stages of diseaseBasel, September 17, 2021 — Novartis today announced positive health-related quality of life (HRQoL) data from its Phase III VISION study evaluating 177Lu-PSMA-617, an investigational targeted radioligand therapy, plus standard of care for metastatic castration-resistant prostate cancer (mCRPC) versus standard of care alone. Many patients with mCRPC live with reduced physical functioning as well as significant pain2,3. This data from a quality of life assessment of the VISION trial, referred to as HRQoL, showed delayed worsening of these difficult to bear symptoms in the 177Lu-PSMA-617 plus standard of care arm compared to standard of care alone arm. No new or unexpected safety concerns, including changes in creatinine clearance, were noted1. These results will be presented at the European Society for Medical Oncology (ESMO) Congress, 17-21 September 2021.HRQoL ad hoc analysis showed that the 177Lu-PSMA-617 plus standard of care arm resulted in an estimated 54% risk reduction in the worsening of HRQoL (measured by Functional Assessment of Cancer Therapy – Prostate (FACT-P) scale) from baseline (hazard ratio: 0.46 with 95% confidence interval (CI): (0.35, 0.61)) compared to the standard of care only arm1. In addition, 177Lu-PSMA-617 plus standard of care also resulted in an estimated 55% risk reduction of worsening of pain intensity (measured by Brief Pain Inventory – Short Form (BPI-SF) scale) from baseline (hazard ratio: 0.45 with 95% (CI): (0.33, 0.60)) compared to the standard of care only arm1.“Patients with mCRPC suffer from many complications associated with advanced disease that can impact their quality of life2,3,” said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development, Novartis. “These new data emphasize the potential impact on quality of life that investigational 177Lu-PSMA-617 may provide as a potential new treatment option, beyond previously reported improvements in overall survival and radiographic progression-free survival4.”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.About Advanced Prostate CancerProstate cancer is a form of cancer that develops in the prostate gland, a small walnut shaped gland in the pelvis of men. In castration resistant prostate cancer (CRPC), the tumor shows signs of growth, such as rising Prostate Specific Antigen (PSA) levels, despite the use of hormone treatments that lower testosterone5. In metastatic CRPC (mCRPC), the tumor spreads to other parts of the body, such as neighboring organs or bones and remains unresponsive to hormone treatment5. The five-year survival rate for patients with metastatic prostate cancer is approximately 30%6.About Phenotypic Precision Medicine in Advanced Prostate CancerDespite advances in prostate cancer care, there is a high unmet need for new targeted treatment options to improve outcomes for patients with mCRPC. More than 80% of prostate cancer tumors highly express a phenotypic biomarker7 called Prostate Specific Membrane Antigen (PSMA) 8-10,11,12, making it a promising diagnostic (through positron emission tomography (PET) scan imaging) and potential therapeutic target for radioligand therapy13. This differs from ‘genotypic’ precision medicine which targets specific genetic alterations in cancer cells7.About 177Lu-PSMA-617177Lu-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)14-16. After administration into the bloodstream, 177Lu-PSMA-617 binds to prostate cancer cells that express PSMA17, a transmembrane protein, with high tumor-to-normal tissue uptake14,18,19. Once bound, emissions from the radioisotope damage tumor cells, disrupting their ability to replicate and/or triggering cell death20-22. The radiation from the radioisotope works over very short distances to limit damage to surrounding cells13,14,18.About VISIONVISION 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 arm4. 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 arm4. The study met both alternate primary endpoints of radiographic progression free survival and overall survival; secondary endpoints were also met4. The study enrolled 831 patients4.DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.About NovartisNovartis 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 109,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.Novartis is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnewsFor Novartis multimedia content, please visit https://www.novartis.com/news/media-libraryFor questions about the site or required registration, please contact [email protected].     Novartis data on File 2.     Kuppen MCP, Westgeest HM, van den Eertwegh AJM et al. Health-related Quality of Life and Pain in a Real-world Castration-resistant Prostate Cancer Population: Results From the PRO-CAPRI Study in the Netherlands. Clin Genitourin Cancer 2020;18(3):e233–e2533.     Sullivan PW, Mulani PM, Fishman M et al. Quality of life findings from a multicenter, multinational, observational study of patients with metastatic hormone-refractory prostate cancer Qual Life Res. 2007;16:571–5754.     Sartor O, J. de Bono KN, Chi K, et al Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. NEJM 2021; doi: 10.1056/NEJMoa21073225.     Kirby M, Hirst C, Crawford ED. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract 2011;65(11):1180–926.     SEER. Cancer stat facts: prostate cancer July 2021. [https://seer.cancer.gov/statfacts/html/prost.html]7.     Sant GR, Knopf KB, Albala DM. Live-single-cell phenotypic cancer biomarkers-future role in precision oncology? NPJ Precision Oncology 2017;1(1):218.     Hupe MC, Philippi C, Roth D, et al. Expression of prostate-specific membrane antigen (PSMA) on biopsies is an independent risk stratifier of prostate cancer patients at time of initial diagnosis. Front Oncol 2018;8:6239.     Bostwick DG, Pacelli A, Blute M, et al. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 1998;82(11):2256–6110.   Pomykala KL, Czernin J, Grogan TR, et al. Total-body 68Ga-PSMA-11 PET/CT for bone metastasis detection in prostate cancer patients: potential impact on bone scan guidelines. J Nucl Med 2020;61(3):405–1111.   Minner S, Wittmer C, Graefen M, et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 2011;71(3):281–812.   Hope TA, Aggarwal R, Chee B, et al. Impact of 68Ga-PSMA-11 PET on management in patients with biochemically recurrent prostate cancer. J Nucl Med 2017;58(12):1956–6113.   Hofman MS, Violet J, Hicks RJ et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol 2018;19(6):825–3314.   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):1170–615.   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):688–97.16.   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):914–2017.   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):9-15.201618.   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):517–2319.   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):2946–55.20.   Kassis A. Therapeutic Radionuclides: Biophysical and Radiobiologic Principles. Semin Nucl Med. 2008; 38(5): 358–36621.   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: 1786–179222.   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# # #Novartis Media RelationsE-mail: [email protected] von TreskowNovartis Global Media Relations+41 79 392 8697 [email protected] Julie MasowNovartis US External Engagement +1 862 579 8456 [email protected] LevineAdvanced Accelerator Applications, a Novartis Company+1 917 375 [email protected] Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: [email protected] North America Samir Shah+41 61 324 7944Sloan Simpson+1 862 345 4440Thomas Hungerbuehler+41 61 324 8425Alina Levchuk+1 862 778 3372Isabella Zinck+41 61 324 7188Parag Mahanti+1 973-876-4912