UKONIQ SIDE EFFECTS

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Infections
• Neutropenia
• Diarrhea and Non-infectious Colitis
• Hepatotoxicity
• Severe Cutaneous Reactions

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 compared to rates in the clinical trials of another drug and may not reflect the rates observed in the general patient population.

The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to UKONIQ as monotherapy at a dosage of 800 mg orally once daily in 335 adults with hematologic malignancies in studies TGR-1202-101, TGR-1202-202, UTX-TGR-205, and UTXTGR- 501. Among these 335 patients who received UKONIQ, 52% were exposed for 6 months or longer and 30% were exposed for greater than one year.

Relapsed Or Refractory Follicular Lymphoma And Marginal Zone Lymphoma

The safety of UKONIQ was evaluated in a pooled safety population that included 221 adults with marginal zone lymphoma (37%) and follicular lymphoma (63%) enrolled in three singlearm, open-label trials (Study TGR-1202-101, TGR-1202-202, and UTX-TGR-205) and one open-label extension trial (Study UTX-TGR-501).These trials required hepatic transaminases ≤ 2.5 times upper limit of normal (ULN), total bilirubin ≤ 1.5 times ULN, and creatinine clearance ≥ 30 mL/min. No patients had prior exposure to a PI3K inhibitor. Patients received UKONIQ 800 mg orally once daily. Among these 221 patients who received UKONIQ, 60% were exposed for 6 months or longer and 34% were exposed for greater than one year.

The median age was 66 years (range: 29 to 88 years), 43% were female, and 97% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Race was reported in 92% of patients; of these patients, 89% were White, 6% were Black, and 3% were Asian. Patients had a median of 2 prior therapies (range 1 to 10).

Serious adverse reactions occurred in 18% of patients who received UKONIQ. Serious adverse reactions that occurred in ≥2% of patients were diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%). Fatal adverse reactions occurred in <1% of patients who received UKONIQ, including exfoliative dermatitis.

Permanent discontinuation of UKONIQ due to an adverse reaction occurred in 14% of patients. Adverse reactions which resulted in permanent discontinuation of UKONIQ in ≥5% of patients included diarrhea-colitis (6%) and transaminase elevation (5%).

Dose reductions of UKONIQ due to an adverse reaction occurred in 11% of patients. Adverse reactions which required dose reductions in ≥4% of patients included diarrhea-colitis (4%).

Dosage interruptions of UKONIQ due to an adverse reaction occurred in 43% of patients. Adverse reactions which required dosage interruption in ≥5% of patients included diarrheacolitis (18%), transaminase elevation (7%), neutropenia (5%), vomiting (5%), and upper respiratory tract infection (5%).

The most common (≥15%) adverse reactions, including laboratory abnormalities, were increased creatinine, diarrhea-colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash.

Table 1 provides the adverse reactions in the pooled safety population of 221 patients with marginal zone lymphoma and follicular lymphoma who received the recommended dosage.

Table 1: Adverse Reactions Reported (≥10%) in Patients With Marginal Zone Lymphoma and Follicular Lymphoma Who Received UKONIQ in Pooled Safety Population

Clinically relevant adverse reactions in <10% of patients who received UKONIQ included urinary tract infection (9%), dyspnea (7%), pneumonia (6%), sepsis (3%), colitis (2%), pneumonitis (<1%), and exfoliative dermatitis (<1%).

Table 2 provides the laboratory abnormalities in the pooled safety population of 221 patients with marginal zone lymphoma and follicular lymphoma who received the recommended dosage.

Table 2: Select Laboratory Abnormalities (≥20%) That Worsened from Baseline in Patients with Marginal Zone Lymphoma and Follicular Lymphoma Who Received UKONIQ in Pooled Safety Population