Breakthrough: Lutathera Shows Significant Progress in Advanced Neuroendocrine Tumor Therapy

Breakthrough: Lutathera Shows Significant Progress in Advanced Neuroendocrine Tumor Therapy

(IN BRIEF) Novartis has announced successful results from its Phase III NETTER-2 trial involving Lutathera, a treatment for neuroendocrine tumors (NETs). When used as a first-line treatment in combination with long-acting octreotide, Lutathera significantly improved progression-free survival in patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) compared to those receiving octreotide alone. The trial also confirmed the safety profile of Lutathera. NETs, though rare, have seen a significant increase in incidence, necessitating more treatment options. This marks Lutathera’s second Phase III success, following the NETTER-1 trial, and offers hope for patients facing this challenging disease. The trial results will be presented at a medical meeting and discussed with regulatory authorities.

(PRESS RELEASE) BASEL, 25-Sep-2023 — /EuropaWire/ — Novartis (SWX: NOVN), a Swiss multinational pharmaceutical company, is pleased to announce the successful outcome of the Phase III NETTER-2 trial involving Lutathera® (INN: lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate). This groundbreaking trial has achieved its primary objective, marking a significant advancement in the treatment of neuroendocrine tumors (NETs).

In the Phase III NETTER-2 trial, Lutathera, when used as a first-line treatment in combination with long-acting octreotide, demonstrated a remarkable improvement in progression-free survival (PFS) for patients diagnosed with somatostatin receptor (SSTR)-positive, Grade 2 and 3, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This improvement in PFS was observed in comparison to patients receiving high-dose long-acting octreotide alone.

Importantly, the study revealed no new or unexpected safety concerns, with the data aligning closely with Lutathera’s well-established safety profile.

Neuroendocrine tumors (NETs) represent a unique category of cancers originating in neuroendocrine cells across the body. While many NETs are characterized by slow growth, some exhibit rapid progression and a grim prognosis. Often, NET diagnoses occur at advanced stages, emphasizing the critical need for more effective treatment options.

The NETTER-2 trial results represent the second Phase III success for Lutathera, following the pivotal NETTER-1 trial, which led to the initial approval of Lutathera. NETTER-1 demonstrated significant and clinically meaningful improvements in PFS for patients treated with Lutathera in combination with long-acting octreotide compared to those receiving high-dose (60 mg) long-acting octreotide. NETTER-1 primarily focused on patients with inoperable midgut neuroendocrine tumors (NETs) who were progressing despite standard treatment.

“These positive results for Lutathera are quite remarkable and they represent the potential for radioligand therapy to make a meaningful impact for newly diagnosed patients living with advanced GEP-NETs,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development at Novartis. “Exploring the use of radioligand therapies in earlier lines of treatment for patients with cancer is part of our larger, collaborative effort to precisely deliver novel treatment modalities directly to the cancer cells to improve patient outcomes.”

The findings from the NETTER-2 trial will be presented at an upcoming medical conference and will be discussed with relevant regulatory authorities. These results hold great promise for patients with advanced neuroendocrine tumors, offering new hope in the fight against this challenging disease.

About NETTER-2
NETTER-2 (NCT03972488) is an open-label, multi-center, randomized, comparator-controlled Phase III trial assessing whether Lutathera plus long-acting octreotide when taken as a first line treatment can prolong PFS in patients with high-proliferation rate tumors (G2 and G3), compared to treatment with high-dose (60 mg) long-acting octreotide². Eligible patients were diagnosed with SSTR-positive advanced GEP-NETs within 6 months before enrollment².

About Lutathera^®
Lutathera^® (INN: lutetium (¹⁷⁷Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate) is an Advanced Accelerator Applications RLT approved in the United States for the treatment of SSTR-positive GEP-NETs, including foregut, midgut and hindgut neuroendocrine tumors in adults and in Europe for unresectable or metastatic, progressive, well-differentiated (G1 and G2), SSTR-positive GEP-NETs in adults^10–11.

Novartis and Radioligand Therapy (RLT)
Novartis is reimagining cancer care with RLT for patients with advanced cancers. By harnessing the power of radioactive atoms and applying it to advanced cancers, RLT is theoretically able to deliver radiation to target cells anywhere in the body^12-13. Novartis has established global expertise, specialized supply chain and manufacturing capabilities across its network of RLT production sites. In order to support growing demand for our RLT platform, we have expanded our RLT production capabilities in Millburn, New Jersey (U.S.), Zaragoza (Spain) and Ivrea (Italy), and are building a new radioligand manufacturing facility in Indianapolis, Indiana (U.S.), which is planned to be operational later in 2023. We are continually evaluating additional opportunities to expand capacity.

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,” “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 Novartis
Novartis is reimagining medicine to improve and extend people’s lives. We deliver high-value medicines that alleviate society’s greatest disease burdens through technology leadership in R&D and novel access approaches. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. About 103,000 people of more than 140 nationalities work together to bring Novartis products to nearly 800 million people around the world. Find out more at https://www.novartis.com

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References

1. Novartis Data on File.
2. ClinicalTrials.gov. NETTER-2 (NCT03972488). Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET (NETTER-2). Accessed September 15, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03972488
3. Strosberg JR, Caplin ME, Kunz PL, et al. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial [published correction appears in Lancet Oncol. 2022 Feb;23(2):e59]. Lancet Oncol. 2021;22(12):1752-1763. doi:10.1016/S1470-2045(21)00572-6
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9. Novartis. Press Release. Available online: https://www.novartis.com/news/media-releases/advanced-accelerator-applications-receives-fda-approval-lutathera-treatment-gastroenteropancreatic-neuroendocrine-tumors. Last accessed September 2023.
10. Lutathera. Full Prescribing Information. 2018. Revised March 2023. https://www.novartis.com/us-en/sites/novartis_us/files/lutathera.pdf
11. Lutathera. Summary of Product Characteristics (SmPC). 2018. Revised February 2023. https://www.ema.europa.eu/en/documents/product-information/lutathera-epar-product-information_en.pdf
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