What Is Darolutamide (Nubeqa)? FDA Approval, Licensing and Reimbursement in Turkey

• FDA approved: Yes (initial approval: July 30, 2019) 
• Brand name: Nubeqa
• Active ingredient: Darolutamide
• Administration: Oral tablet
• Class: Antiandrogens, hormones/antineoplastic agents
• Category: Hormonal medicine
• Manufacturer: Bayer HealthCare Pharmaceuticals Inc. 
• Distributor in Turkey: Bayer
• Approved cancer indications: Prostate cancer

What Is Nubeqa?

Nubeqa, containing the active ingredient darolutamide, is an antineoplastic medicine known as a second-generation androgen receptor inhibitor (ARi). It is used particularly in the treatment of prostate cancer and targets the function of androgen receptors (AR) to stop the growth of prostate cancer cells.

Mechanism of Action:

Darolutamide binds to androgen receptors and inhibits them, preventing androgens such as testosterone from binding to these receptors. Normally, testosterone binds to these receptors and triggers gene expression within the cell, sending signals that accelerate cell division. Prostate cancer cells have become dependent on this process.

Darolutamide inhibits both wild-type androgen receptors and mutant receptors. This means it may also stop the growth of cells that have developed resistance to certain other antiandrogens. By binding to the receptors, darolutamide:

1. Blocks androgen binding.
2. Inhibits androgen receptor transport to the nucleus (movement into the nucleus).
3. Stops DNA interaction and gene transcription.

These effects inhibit tumor cell growth and stop cancer progression. One of darolutamide's most important features is its lower penetration of the blood-brain barrier compared with similar medicines, resulting in fewer central nervous system side effects, particularly a lower risk of seizures.

FDA Approval History:

• June 3, 2025: Darolutamide Receives New FDA Approval in Metastatic Castration-Sensitive Prostate Cancer
• August 5, 2022: Nubeqa was approved for use in metastatic hormone-sensitive prostate cancer in combination with docetaxel.
• July 30, 2019: It received its first FDA approval for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC).

Licensing in Turkey:

Nubeqa, containing darolutamide, is licensed by the Turkish Ministry of Health for the following indications.

• For adult men with nonmetastatic castration-resistant prostate cancer at high risk of developing metastatic disease (PSA doubling time ≤ 10 months and PSA level above 2 ng/ml), with an ECOG performance status of 0-1.

• In combination with docetaxel and androgen deprivation therapy for adult men with metastatic hormone-sensitive prostate cancer (mHSPC) and high-volume disease (visceral metastases or ≥ 4 bone metastases, with at least 1 outside the spine and pelvis). Docetaxel must be started within the first 6 weeks after the initial NUBEQA dose.

Is It Reimbursed?

It is covered by Turkey's Social Security Institution (SGK).

• The Institution reimburses its use in adult men with nonmetastatic castration-resistant prostate cancer (nmCRPC), an ECOG performance status of 0-1 and a high risk of metastasis (PSA doubling time ≤ 6 months, N0-1, PSA level above 2 ng/dl, testosterone at castration levels (<50 ng/dl), and no previous cytotoxic chemotherapy).
• It is indicated in combination with docetaxel and androgen deprivation therapy for adult men with metastatic hormone-sensitive prostate cancer (mHSPC) and high-volume disease (visceral metastases or ≥ 4 bone metastases, with at least 1 outside the spine and pelvis). Docetaxel must be started within the first 6 weeks after the initial darolutamide dose.
• The Institution reimburses sequential use of medicines containing enzalutamide, apalutamide, darolutamide and abiraterone only when the Ministry of Health has granted off-label medicine use approval.

Price: As of August 2025, the pharmacy retail price for Nubeqa film-coated tablets, 300 mg, a pack of 112 tablets, is 47153.56  Turkish lira.

Resistance Mechanism:

Prostate cancer cells can develop resistance to androgen suppression. Darolutamide interacts with androgen receptors more specifically and effectively to overcome this resistance, making it less susceptible to mechanisms of resistance that develop against other antiandrogen medicines.

Absorption:

Darolutamide's oral bioavailability increases 2 to 2.5 times when taken with food. Absorption is dose-dependent, and maximum plasma concentration is reached in approximately 4 hours.

Distribution:

Darolutamide is 92% bound to plasma proteins. Its keto-darolutamide form is 99.8% protein-bound.

Metabolism:

The medicine is metabolized primarily in the liver by CYP3A4 and UGT1A9/UGT1A1 enzymes. One metabolite, keto-darolutamide, is biologically active, but only a small proportion circulates freely.

Dosage Range:

• Nonmetastatic Castration-Resistant Prostate Cancer: 600 mg twice daily.
• Metastatic Hormone-Sensitive Prostate Cancer: 600 mg twice daily, in combination with docetaxel.

Drug Interactions:

• CYP3A4 inhibitors: They may increase plasma darolutamide levels, raising the risk of side effects.
• CYP3A4 inducers: They may reduce the medicine's effectiveness.
• P-glycoprotein and BCRP inhibitors: They may cause darolutamide to interact with other medicines.

Precautions:

• Ischemic heart disease: Patients at risk of ischemic heart disease should be monitored carefully.
• Seizure risk: Darolutamide may increase the risk of seizures.
• Pregnancy: Male patients should use effective contraception to prevent pregnancy.

Side Effects:

The most common side effects are:

1. Fatigue
2. Pain in the arms and legs
3. Rash
4. Low white blood cell count
5. Abnormal liver function tests

Less common side effects include:

1. Ischemic heart disease
2. Seizures
3. Pulmonary embolism
4. Infections