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Novartis prostate cancer drug extends survival in key test of radiopharmaceutical therapy

A radioactive particle, delivered precisely to prostate cancer cells in men whose disease had spread, helped slow tumor growth and extend survival, results from a late-stage study run by the medicine’s developer Novartis show.

Treatment with the so-called radioligand therapy, which was given alongside standard drugs, cut the risk of death by nearly 40% compared to those drugs alone. Participants who received Novartis’ therapy in the clinical trial also went a median of five months longer before their cancer progressed.

The study results were disclosed Thursday ahead of the American Society of Clinical Oncology’s annual meeting and will be presented online over the weekend.

Radioligand therapy builds on decades of experience with using radiation to destroy fast-dividing cancer cells, extending that approach into an era of targeted treatment. Radioactive isotopes are bound to a small molecule that’s designed to guide the resulting medicine to cells showing certain protein flags. In prostate cancer, the target protein is called PSMA and highly expressed on tumors in about 80% of patients.

Critically, PSMA is not typically expressed at high levels on healthy cells, allowing for more selective treatment of tumor cells.

“Radioligand therapy is sort of like targeted delivery of radioactive isotopes,” said Jeff Legos, global head of oncology development at Novartis. “We use a small molecule, or peptide, as a GPS to deliver this radioactive lutetium to the cancer cells,” he added, referring to the specific isotope contained in the drugmaker’s medicine, known by technical name 177Lu-PSMA-617.

Radioligand therapy is sometimes referred to as radiopharmaceutical therapy.

With results from the study positive, Novartis plans to ask regulators in the U.S. and Europe for clearance of the medicine.

“Use of this PSMA radioligand therapy, if it obtains regulatory approval, could indeed become an important treatment option for these patients with refractory disease,” said Lori Pierce, president of ASCO and a radiation oncologist, in a conference call ahead of this weekend’s meeting.

For its study, Novartis enrolled 831 men with metastatic, castration-resistant prostate cancer that was positive for PSMA. Participants were sick, having previously received hormone therapy as well as one to two chemotherapy regimens.

About two-thirds of the trial participants received the radioligand therapy together with standard drugs chosen by their physician, while the other third were only given standard treatment.

The study met all of the primary and secondary goals set by Novartis. Median overall survival — considered the most definitive measure of a cancer drug’s benefit — was 15.3 months among those who received Novartis’ drug and 11.3 months among those who didn’t.

A comparison of median progression free survival, as measured by radiographs of patient tumors, also showed a benefit to the experimental treatment, with a 60% reduction in risk versus standard drugs.

Radioligand therapy was associated with much higher rates of side effects, however. Roughly 28% of participants on 177Lu-PSMA-617 experienced “treatment-emergent” adverse events classified as severe, compared to about 4% in the control group. Low blood cell counts, fatigue and dry mouth were the most common side effects reported in the study.

Novartis’ Legos explained those side effects were generally expected, as the healthy cells that do express PSMA are typically found in the bone marrow, salivary gland and kidney. (Rates of kidney-related side effects were slightly higher among patients who received the radioligand therapy.)

Along with being the treatment target, PSMA also functions as a biomarker by which patients were selected for the study.

Michael Morris, the study’s lead author, noted the enrollment criteria for Novartis’ trial were more inclusive than past clinical tests of radioligand therapies.

“Even with the looser criteria, you saw the survival advantage and the [progression-free survival] advantage,” Morris said in a press conference ahead of the meeting. “It is nice to see that with relatively lax criteria for allowability that [in] the general population the majority of those patients are eligible and would benefit from this treatment.”

About 70% of people screened for the study were enrolled, according to a study abstract.

Novartis has begun opening sites for two studies testing 177Lu-PSMA-617 in earlier lines of treatment, both before chemotherapy and in patients whose cancers are still responsive to hormone therapy. Dosing of the first patients in both studies is expected to begin “imminently,” according to Legos, and the trials could deliver results by 2023 or 2024.

Novartis acquired 177Lu-PSMA-617 through its 2018 buyout of Endocyte, one of a series of investments the Swiss drugmaker has made in radioligand therapies. That same year Novartis won U.S. approval for Lutathera, a radioligand drug it had bought through an earlier takeover of Advanced Accelerator Applications.

Other large pharmaceutical companies, including Bayer and AstraZeneca, are also pursuing research on drug candidates using radioisotopes, including for prostate cancer.

On Thursday, Bayer announced it would buy two small biotech companies that are developing a radioisotope-containing therapy targeted at PSMA.