ASCO: Novartis' radiotherapy ambition takes a small hit as Lutathera relegated to 'clinically relevant' survival edge

Novartis headquarters
Novartis' Lutathera extended the lives of patients with midgut neuroendocrine tumors by nearly a year, but the difference was not statistically significant. (Novartis)

Radiopharmaceuticals, along with cell and gene therapy, is one of the advanced drug platforms Novartis has pegged for long-term growth. But that ambition has hit a small setback.

Lutathera, the first radioligand therapy Novartis introduced to the market, failed to significantly prolong the lives of patients with midgut neuroendocrine tumors, according to data unveiled at the American Society of Clinical Oncology.

When used alongside Novartis’ own Sandostatin LAR in the phase 3 Netter-1 trial, Lutathera reduced the risk of death by 16% compared with solo Sandostatin LAR. But the improvement didn’t clear the statistical significance bar.

But Jonanthan Strosberg, M.D., principal investigator of the trial, was quick to note that adding Lutathera to the mix extended the median time patients lived by nearly a year; patients treated with the Lutathera regimen lived a median 48 months, versus 36.3 months for the control group.

“While not statistically significant, I consider this difference to be clinically relevant for these patients,” Strosberg said in a statement.

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Multiple factors may have hurt Lutathera’s survival stats, Novartis said. A large number of patients in the control arm—about 36%—actually crossed over to receive Lutathera, Strosberg noted. Patients in the Netter-1 trial were allowed to receive other anti-cancer treatments after disease progression on their randomized treatment or upon finishing an 18-month treatment period.

Lutathera earned its initial FDA go-ahead in early 2018 for gastroenteropancreatic neuroendocrine tumors, after Netter-1 showed it could reduce the risk of disease progression or death by a whopping 79%. At that time, a planned interim analysis pointed to an estimated 48% reduction in the risk of death for Lutathera.

For a rare cancer type, Lutathera brought in sales of $445 million in 2020, in line with the prior year. The drug has so far been administered to more than 9,000 patients in Europe and U.S., according to Novartis Chief Medical Officer John Tsai.

“We believe in the potential of targeted radioligand therapy and are investing in new discovery and expansion of this important platform, including exploration of new radioisotopes and combinations with complementary mechanisms of action, such as immunotherapy and inhibitors of DNA damage response,” Tsai said in a statement Thursday.

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Lutathera came to Novartis by way of its acquisition of Advanced Accelerator Applications. Netter-1 tested it in patients with well-differentiated, or G1, tumors. Novartis is now testing the drug in newly diagnosed patients with moderately- or poorly differentiated G2 and G3 tumors.

Also at ASCO, Novartis reported a phase 3 win for another radiotherapy dubbed 177Lu-PSMA-617, which it scored via the $2.1 billion buyout of Endocyte. The drug reduced the risk of death by 38% in patients with metastatic castration-resistant prostate cancer.

In addition to AAA and Endocyte, the Swiss drugmaker recently licensed rights to radioligand treatments targeting fibroblast activation protein, or FAP, from iTheranostics.