NUBEQA SIDE EFFECTS

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Non-Metastatic Castration Resistant Prostate Cancer

The safety of NUBEQA was evaluated in ARAMIS, a randomized (2:1), double-blind, placebo-controlled, multi-center clinical study, that enrolled patients who had non-metastatic castration-resistant prostate cancer (nmCRPC). Patients received either NUBEQA at a dose of 600 mg, or a placebo, twice a day. All patients in the ARAMIS study received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. Among patients who received NUBEQA, the median duration of exposure was 14.8 months (range: 0 to 44.3 months).

Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo.

Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo. Fatal adverse reactions in patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%).

Permanent discontinuation of NUBEQA due to adverse reactions occurred in 9% of patients receiving NUBEQA. The most common adverse reactions requiring permanent discontinuation in patients who received NUBEQA included cardiac failure (0.4%), and death (0.4%).

Dosage interruptions due to adverse reactions occurred in 13% of patients treated with NUBEQA. The most common adverse reactions requiring dosage interruption in patients who received NUBEQA included hypertension (0.6%), diarrhea (0.5%), and pneumonia (0.5%).

Dosage reductions due to adverse reactions occurred in 6% of patients treated with NUBEQA. The most common adverse reactions requiring dosage reduction in patients treated with NUBEQA included fatigue (0.7%), hypertension (0.3%), and nausea (0.3%).

The most common (>2% with a ≥2% increase compared to placebo) adverse reactions, including laboratory test abnormalities, were AST increased, neutrophil count decreased, fatigue, bilirubin increased, pain in extremity, and rash.

Table 1 summarizes the adverse reactions in ARAMIS.

Table 1: Adverse Reactions (>2% with a ≥2% increase compared to placebo) in Patients with Non-Metastatic Castration Resistant Prostate Cancer in ARAMIS

Clinically relevant adverse reactions occurring in 2% or more of patients treated with NUBEQA included ischemic heart disease (4%) and heart failure (2.1%).

Table 2 summarizes the laboratory test abnormalities in ARAMIS.

Table 2: Laboratory Test Abnormalities in ARAMIS

Metastatic Hormone-Sensitive Prostate Cancer

The safety of NUBEQA, in combination with docetaxel, was evaluated in ARASENS, a randomized (1:1), double-blind, placebo-controlled, multi-center clinical study, that enrolled patients who had mHSPC. Patients were to receive either NUBEQA at a dose of 600 mg, or a placebo, twice a day in combination with docetaxel at a dose of 75 mg/m² every 21 days for 6 cycles. All patients in the ARASENS study received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. Patients with a medical history of seizure were allowed to enter the study. Among patients who received NUBEQA, the median duration of exposure was 41 months (range: 0.1 to 56.5 months) vs. 16.7 months (range 0.3 to 55.8) with placebo. Eighty-eight percent and 86% of patients received the 6 planned cycles of docetaxel, in the NUBEQA with docetaxel arm and placebo with docetaxel arm, respectively.

Serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel and in 42% of patients receiving placebo with docetaxel, respectively. Serious adverse reactions in ≥ 2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), neutrophil count decreased (2.8%), musculoskeletal pain (2.6%) and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel and 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID­19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%).

Permanent discontinuation of NUBEQA due to adverse reactions occurred in 14% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions which resulted in permanent discontinuation of NUBEQA were rash (1.1%), musculoskeletal pain (0.9%), and aspartate aminotransferase (AST) increased (0.9%).

Dosage interruptions of NUBEQA due to adverse reactions occurred in 23% of patients treated in the NUBEQA with docetaxel arm. The most common (>2%) adverse reactions requiring dosage interruption of NUBEQA were alanine aminotransferase (ALT) increased (3.2%), AST increased (3.1%) and febrile neutropenia (2.1%).

Dosage reductions of NUBEQA due to adverse reactions occurred in 9% of patients treated in the NUBEQA with docetaxel arm. The most common (>2%) adverse reactions requiring dosage reduction of NUBEQA were ALT increased (2.8%) and AST increased (2.5%).

The most common (>10% with a ≥2% increase over placebo with docetaxel) adverse reactions are constipation, decreased appetite, rash, hemorrhage, weight increased, and hypertension. The most common laboratory test abnormalities (≥30%) are anemia, hyperglycemia, lymphocyte count decreased, neutrophil count decreased, AST increased, ALT increased, and hypocalcemia.

Table 3 summarizes the adverse reactions in ARASENS.

Table 3: Adverse Reactions (≥10% with a ≥2% increase compared to placebo with docetaxel) in ARASENS

Clinically relevant adverse reactions in < 10% of patients who received NUBEQA with docetaxel included fractures (8%), ischemic heart disease (2.9%), seizures (0.6%), and drug-induced liver injury (0.3%).

Table 4 summarizes laboratory test abnormalities in the ARASENS study.

Table 4: Laboratory Test Abnormalities (≥30%) in ARASENS

Clinically relevant laboratory test abnormalities in < 30% of patients who received NUBEQA with docetaxel included blood bilirubin increased (all grades 20%, Grade 3-4 0.5%) compared to placebo with docetaxel (all grades 10%, grades 3-4 0.3%).