Pluvicto® demonstrated consistent efficacy across key patient subgroups in metastatic hormone-sensitive prostate cancer

• Improved radiographic progression-free survival (rPFS) regardless of disease volume or metastatic presentation achieved with Pluvicto plus standard of care (ARPI + ADT) in PSMAddition
• Consistent secondary endpoint results, including PSA progression and time to mCRPC, and safety profile reinforce broad clinical applicability
• Promising Phase 1 data for Novartis actinium-based RLT also presented, supporting two Phase 3 trials and reinforcing Novartis global RLT leadership

East Hanover, May 31, 2026 – Novartis today announced results showing consistent radiographic progression-free survival (rPFS) improvement across key subgroups with Pluvicto^® (lutetium Lu 177 vipivotide tetraxetan) plus standard of care (SoC; androgen receptor pathway inhibitor [ARPI] + androgen deprivation therapy [ADT]) compared to SoC alone in PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC). These PSMAddition data were presented as an oral presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.

The subgroup analysis evaluated outcomes by disease volume (high or low) and disease presentation (de novo or recurrent mHSPC). Pluvicto demonstrated a similar rPFS improvement across key subgroups, consistent with the previously reported primary endpoint showing a 28% reduction in the risk of radiographic progression or death (HR 0.72; 95% CI: 0.58, 0.90). Secondary endpoints for disease progression were also consistent. Together, these data support use of Pluvicto as early as PSMA+ metastatic prostate cancer diagnosis.

Subgroup	rPFS hazard ratio for Pluvicto arm vs. control arm
Overall (n=1,144)	0.72 (0.58 – 0.90)
High volume disease (n=779)	0.72 (0.56 – 0.92)
Low volume disease (n=365)	0.73 (0.42 – 1.27)
De novo (n=572)	0.74 (0.54 – 1.01)
Recurrent (n=523)	0.74 (0.53 – 1.04)
Disease volume per CHAARTED criteria; data from second interim analysis for rPFS, DCO 13 Jan 2025

“Metastatic hormone-sensitive prostate cancer is a heterogeneous disease, with disease burden and presentation often dictating how aggressively a patient’s cancer will progress,” said Fred Saad, Professor and Chairman, Department of Surgery, University of Montreal. “The consistent findings demonstrated with Pluvicto across key subgroups, regardless of initial presentation or disease volume, reinforce its potential as a cornerstone of early treatment for a broad range of patients.”

The safety profile was generally consistent across subgroups within each treatment arm, with similar incidence of adverse events (AEs). In PSMAddition, Grade ≥3 AEs were reported in 50.7% of patients in the Pluvicto plus SoC arm, compared to 43% on SoC alone. The most common all-grade AEs were dry mouth, fatigue, nausea, hot flush and anemia.

More than 186,000 men are diagnosed annually with mHSPC, now also known as metastatic androgen pathway modulation-naïve/sensitive prostate cancer (mAPMN/S), globally^*1. Most patients progress to castration-resistant, or modulation-resistant (mAPMR) disease within 20 months^2,3. The PSMA biomarker is present in more than 80% of patients with prostate cancer^4-8.

Novartis has filed regulatory submissions in the US, China and Japan based on results from PSMAddition, with first decisions expected in H2 2026.

Promising Phase 1 data from AcTION for actinium-based RLT ²²⁵Ac-PSMA-617
Novartis also presented data for its actinium-based RLT, ²²⁵Ac-PSMA-617, from the Phase 1 AcTION trial. The data showed promising early antitumor activity with PSA declines and radiographic responses, as well as a manageable safety profile which supports further clinical development in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC).

“Novartis helped redefine treatment for metastatic prostate cancer with Pluvicto, and we are continuing to push the bar even higher,” said Mark Rutstein, Global Head of Oncology Development at Novartis. “Our actinium program represents the next frontier in radioligand therapy, and with two Phase 3 trials underway, we are working to extend the promise of RLTs to more patients.”

²²⁵Ac-PSMA-617 is an investigational actinium-based RLT that targets PSMA with a proven ligand to deliver short-ranged, high-energy alpha-particle radiation directly to prostate cancer cells. ²²⁵Ac-PSMA-617 is designed to induce potent tumor cytotoxicity while minimizing exposure to surrounding healthy tissues, reflecting Novartis’ strategy to advance differentiated RLTs across multiple disease stages.

Novartis is enrolling two Phase 3 trials for ²²⁵Ac-PSMA-617:

• PSMAcTION evaluating ²²⁵Ac-PSMA-617 in mCRPC after Pluvicto, chemotherapy and ARPI
• AcTFirst evaluating ²²⁵Ac-PSMA-617 in frontline mCRPC

Radioligand Therapy (RLT) at Novartis
Novartis is reimagining cancer care with RLT for patients with advanced cancers. By harnessing the power of targeted radiation, RLT is designed to deliver treatment directly to target cells anywhere in the body. 

As a global leader in this space, Novartis has built integrated capabilities across research, manufacturing, logistics, and patient and provider support to help ensure approved RLTs reach patients reliably and efficiently. Novartis is investigating a broad portfolio of isotopes, ligands, and combination therapies to expand the use of RLT beyond prostate and neuroendocrine tumors.

Important Safety Information for Pluvicto

What is PLUVICTO^® (lutetium Lu 177 vipivotide tetraxetan)?

PLUVICTO is a prescription treatment used to treat adults with prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer (PSMA-positive mCRPC) already treated with:

• hormone therapy and are considered appropriate to delay chemotherapy or
• hormone therapy and chemotherapy

IMPORTANT SAFETY INFORMATION
What is the most important information I should know about PLUVICTO?

Use of PLUVICTO involves exposure to radioactivity. Long-term, accruing radiation exposure is associated with an increased risk for cancer. Drink plenty of water and urinate as often as possible during the first hours after administration.

To minimize radiation exposure to others following administration of PLUVICTO, limit close contact (less than 3 feet) with household contacts for 2 days or with children and pregnant women for 7 days. Refrain from sexual activity for 7 days, and sleep in a separate bedroom from household contacts for 3 days, from children for 7 days, or from pregnant women for 15 days.

PLUVICTO may cause serious side effects, including:

Low level of blood cell counts. Tell your doctor right away if you develop any new or worsening symptoms, including:

• Tiredness or weakness
• Pale skin
• Shortness of breath
• Bleeding or bruising more easily than normal or difficulty stopping bleeding
• Frequent infections with signs such as fever, chills, sore throat, or mouth ulcers

Kidney problems. You should stay well-hydrated before and after treatment. Tell your doctor right away if you develop any new or worsening urinary symptoms.

All radiopharmaceuticals, including PLUVICTO, have the potential to cause harm to an unborn baby.

• You should use effective contraception during treatment with PLUVICTO and for 14 weeks after your last dose

PLUVICTO may cause temporary or permanent infertility.

The most common side effects of PLUVICTO include:

• Decreased blood cell counts
• Tiredness
• Dry mouth
• Nausea
• Appetite loss
• Joint pain
• Constipation
• Back pain

These are not all of the possible side effects of PLUVICTO. Call your doctor for advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full Prescribing Information.

Disclaimer
This 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,” “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; 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 Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 300 million people worldwide.

Reimagine medicine with us: Visit us at https://www.novartis.us and connect with us on LinkedIn US, X/Twitter US and Instagram US.

*Global incidence includes the United States, China, Japan, France, Germany, Italy, Spain and the United Kingdom

References

1. Novartis data on file.
2. Verry C, Vincendeau S, Massetti M, et al. Pattern of clinical progression until metastatic castration-resistant prostate cancer: an epidemiological study from the European Prostate Cancer Registry. Target Oncol. 2022;17(4):441-451.
3. Wenzel M, Siech C, Hoeh B, et al. Contemporary treatment patterns and oncological outcomes of metastatic hormone-sensitive prostate cancer and first- to sixth- line metastatic castration-resistant prostate cancer patients. Eur Urol Open Sci. 2024;66:46-54.
4. 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;8:623.
5. 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):2256-2261.
6. 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):281-288.
7. 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):1956-1961.
8. 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):405-411.