The U.S. Food and Drug Administration (FDA) has approved Erleada (apalutamide) for the treatment of men with metastatic castration-sensitive prostate cancer (mCSPC), or those whose cancer still responds to androgen deprivation therapy (ADT).

The decision is based on the double-blind TITAN Phase 3 trial (NCT02489318), as it showed that adding Janssen’s Erleada to ADT significantly extended both overall survival and progression-free survival (PFS) – the period without cancer progression –, which were the trial’s primary goals.

Compared to ADT and a placebo, treatment with Erleada and ADT reduced the risk of death by 33%, and the likelihood of disease worsening (as assessed by radiography) or death by 52%.

After a median follow-up of 22.7 months, 84% of the patients on Erleada and ADT reached the two-year mark alive, compared to 78% of those on ADT and placebo.

TITAN included 1,052 mCSPC patients regardless of extent of disease and of being newly diagnosed or having been treated with up to six cycles of docetaxel. It was funded by Johnson & Johnson-owned Aragon Pharmaceuticals and Janssen Research and Development (also owned by Johnson & Johnson).

The frequency of serious adverse events was 19.8% for Erleada and 20.3% for placebo. A total of 42 and 28 patients (8% and 5.3%) discontinued treatment because of adverse events. Also, adverse events leading to death occurred in 10 (1.9%) patients on Erleada and in 16 (3.0%) on placebo.

The study’s findings were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine.

Erleada is an oral therapy that targets the androgen receptor, blocking its activation by androgens such as testosterone. In turn, ADT, a mainstay of prostate cancer treatment, reduces the amount of androgens in the body.

“Prostate cancer is more difficult to treat once it spreads, and for patients with castration-sensitive disease, it is clear that androgen deprivation therapy alone is often not enough,” Kim Chi, principal investigator in TITAN and medical oncologist at BC Cancer-Vancouver, said in a press release. “Results from the TITAN study showed that, regardless of the extent of disease, patients with metastatic castration-sensitive prostate cancer have the potential to benefit from treatment with [Erleada] in addition to ADT.”

Margaret Yu, MD, Janssen Research & Development’s vice president and prostate cancer disease area leader, said Erleada may change “how patients with prostate cancer are treated … by delaying disease progression and prolonging survival.” Yu added that the FDA’s approval “highlights Janssen’s commitment to improve the standard of care for patients with prostate cancer as we continue to develop innovative treatments.”

Taking together TITAN and the SPARTAN Phase 3 trial (NCT01946204), the adverse reactions at least 2% more frequent in patients on Erleada than in those on a placebo were fatigue, joint pain, rash, reduced appetite, falls, weight loss, hypertension, hot flush, diarrhea, and fractures.

The approval follows the FDA’s assessment of Janssen’s supplemental New Drug Application under the Real-Time Oncology Review program, which enables the agency to start reviewing clinical data before an official application has been submitted.

Based on results from SPARTAN, Erleada had already been approved as a treatment for patients with non-metastatic (localized) castration-resistant prostate cancer in both the United States and the European Union. In this indication, Earleada decreased the risk of cancer spreading or death by 72 percent compared to a placebo, and delayed the cancer’s metastasis by more than two years.

Janssen said this decision to broaden Erleada’s indications will make the therapy available for the nearly 40,000 people diagnosed with mCSPC every year in the U.S.