The two companies have completed the phase III clinical trial (ARAMIS) of darolutamide, the novel oral androgen receptor antagonist for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).
The primary endpoint of the trial was met: Darolutamide significantly extended metastasis-free survival compared to placebo. The safety profile and the tolerability of darolutamide observed in the ARAMIS trial were consistent with previously published data on darolutamide.
Bayer plans to discuss the data from the ARAMIS trial with health authorities regarding the submission for marketing authorization application. As a rule, Orion will provide information on the progress of the marketing authorization application process in a press release or in its financial reports. Darolutamide has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment in men with nmCRPC.
The ARAMIS trial
Commenced in 2014, the ARAMIS trial evaluated the efficacy and safety of darolutamide in patients with non-metastatic castration-resistant prostate cancer who are currently being treated with androgen deprivation therapy (ADT) as standard of care and are at risk of developing metastatic disease. In the double-blind, placebo-controlled trial, more than 1,500 patients were randomized to receive 600 mg of darolutamide or matching placebo twice a day. The primary endpoint was metastasis-free survival, defined as time between randomization and evidence of metastasis or death from any cause.
Darolutamide was developed jointly by Orion and Bayer, and the partnership was announced in a stock exchange release on 2 June 2014. Bayer has covered the majority of the darolutamide development costs. According to the agreement, Bayer has the right to commercialize darolutamide globally while Orion has the option of co-promoting the product in Europe. In addition, Orion will manufacture the product for global markets. Orion is eligible to receive milestone payments from Bayer upon first commercial sale of darolutamide as follows:
- EUR 45 million upon first commercial sale in the United States
- EUR 20 million upon first commercial sale in the EU
- EUR 8 million upon first commercial sale in Japan
Besides milestone payments, Orion will also receive tiered royalties on the product sales, which will be approximately 20 percent, including production revenue. With sales increase, royalties may increase slightly. Orion also has the possibility to receive one-off payments from Bayer if certain sales targets are met.
In addition to the completed ARAMIS trial, Orion and Bayer have an ongoing phase III clinical trial (ARASENS) which evaluates the safety and efficacy of darolutamide in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Expected to be completed in 2022, there are no separate milestone payments related to the ARASENS trial.
“Prostate cancer is the second most commonly diagnosed malignancy in men in worldwide, and approximately 70 percent of patients have the non-metastatic form of the disease. While conventional hormone therapy is effective in the treatment of non-metastatic cancer, the efficacy is often eventually lost as the sole form of treatment. Additional treatment options in the early stages of the cancer that delay the time to metastases with a manageable safety profile are long awaited. They are significant for the patient’s overall well-being,” says Christer Nordstedt, Senior Vice President, Research and Development at Orion.
Photo of Christer Nordstedt, Senior Vice President, Research and Development at Orion: Orion