Octreotide depot (GP Pharm SA)

The phase 3 win allows Novartis to "really move forward in educating the community" about Lutathera's benefits as a first-line therapy in certain neuroendocrine tumors, CEO Vas Narasimhan recently said. Novartis hopes new data will open a $1 billion market opportunity for its radioligand therapy, Lutathera, as a first-line treatment.  Friday, the company’s ambition received a boost from the phase 3 readout of the NETTER-2 trial. In the study, Lutathera, plus long-acting release (LAR) octreotide, slashed the risk of disease progression or death by 72% versus high-dose octreotide LAR alone in newly diagnosed patients with grade 2 or 3 advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that are somatostatin receptor (SSTR)-positive. Patients in the Lutathera arm went a median 22.8 months without progression, compared with 8.5 months for those in the control arm. The data were shared at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. The Lutathera results offer “a new, safe treatment option in a field with no established standard of care,” lead study author Simron Singh, M.D., from the University of Toronto said in a statement facilitated by ASCO. Lutathera’s current situation in the U.S. is a bit awkward. As Novartis CEO Vas Narasimhan noted during an investor call in October, Lutathera technically enjoys a broad indication that covers its first-line use in the U.S. Thanks to an FDA approval in 2018, the radioligand therapy can be used in SSTR-positive GEP-NETs regardless of a patient’s prior treatment history. But because the approval-enabling NETTER-1 trial was only conducted in patients with previously treated disease and in those with grade 1 and 2 tumors, the majority of Lutathera patients in the real world are getting the drug in the second line. “In the case of the U.S., we wouldn't need further label expansion,” Narasimhan said of the new NETTER-2 win. “And we plan to really move forward in educating the community on the importance of this data to move Lutathera into frontline setting.” A Novartis spokesperson confirmed to Fierce Pharma that the company won’t submit for a supplemental new drug application in the U.S. Outside the U.S., Novartis recently said it plans to file for a frontline grade 3 tumor indication in Europe this year. The spokesperson said the company isn’t able to offer more specific timings at this point. Novartis believes Lutathera could notch more than $1 billion in peak sales as a first-line therapy. In the first nine months of 2023, Lutathera chalked up $458 million in sales, good for growth of 34% growth year over year. By the Swiss pharma’s calculations, more than half of GEP-NET patients in the U.S. are treated in the first-line setting, compared with 30% in the second line and around 10% to 15% in the third line. The company estimates that the U.S. has about 170,000 NET patients, with roughly 55% to 70% of them being GEP-NET cases. Novartis needs to move fast, as the market for progressive NET is likely to get crowded. Exelixis and partner Ipsen recently celebrated positive phase 3 results for their drug Cabometyx in patients with previously treated NET arising in the pancreas or elsewhere. Exelixis is working with the Alliance for Clinical Trials in Oncology, which conducted the phase 3 study, to discuss a potential filing with the FDA this year, the California company said a few days ago. Besides Lutathera’s first-line use, Novartis is also focusing on a potential market expansion for another approved radioligand therapy, Pluvicto, which recently showed that it can stave off disease worsening when used before chemotherapy in PSMA-positive, metastatic castration-resistant prostate cancer. Still, unfavorable but immature survival data from the trial have forced the company to postpone an FDA filing pending a longer follow-up. Novartis figured the pre-chemo setting and a potential expansion in metastatic hormone-sensitive prostate cancer could together translate into more than $2 billion in peak sales for Pluvicto.

Lantheus announced Thursday that the FDA has accepted its application to market a generic version of Novartis' Lutathera (lutetium Lu 177 dotatate). The radiopharmaceutical is currently approved in the US as a treatment for somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (NETs) in adults.If the FDA signs off on the generic version, dubbed 177Lu-PNT2003, Lantheus said it believes it would be the first applicant to have filed a substantially complete ANDA for Lutathera containing a Paragraph IV certification under provisions of the Hatch-Waxman Act, and that it would be eligible for 180 days of generic marketing exclusivity in the US.Lutathera became the first peptide receptor radionuclide therapy to secure approval when the FDA signed off on it in 2018. That decision was based on pivotal NETTER-1 data showing that adding it to standard care with octreotide LAR led to a 79% reduction in the risk of disease progression or death in patients with inoperable midgut NETs, compared to octreotide LAR alone. The treatment was originally developed by Advanced Accelerator Applications, which was subsequently acquired by Novartis for around $3.9 billion.Lantheus licensed commercialisation rights to 177Lu-PNT2003, along with another radiotherapeutic agent, from POINT Biopharma at the end of 2022 for up to $2.2 billion. Earlier this week, Lantheus also paid $28 million upfront for an option to exclusively license Perspective Therapeutics' radiopharmaceutical Pb212-VMT-⍺-NET, which is in a Phase I/II trial to treat NETs.Meanwhile, Novartis has been working to boost its manufacturing capabilities for radioligand therapies, including the prostate cancer treatment Pluvicto (lutetium 177 vipivotide tetraxetan). Last week, the company announced that the FDA had authorised a new production facility in Indianapolis, Indiana.