What are the benefits of this drug (results of trials used to assess efficacy)?

The table below summarizes efficacy results established on the basis of the rate of complete remission (CR)/complete remission with partial hematologic recovery (CRh), the duration of CR/CRh (DOR), and the rate of conversion from transfusion dependence.

Table 2: Efficacy Results in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)-Trial 1

CI: confidence interval; NE: not estimable; NR: not reached; Only responses prior to HSCT were included in response rate.

*CR was defined as an absolute neutrophil count ≥1.0 x 109/L, platelets ≥100 x 109/L, normal marrow differential with <5% blasts, must have been red blood cells, platelet transfusion independent and no evidence of extramedullary leukemia.

†CRh was defined as marrow blasts <5%, partial hematologic recovery absolute neutrophil count ≥0.5 x 109/L and platelets ≥50 x 109/L, no evidence of extramedullary leukemia and could not have been classified as CR.

‡The 95% CI rate was calculated using the exact method based on binomial distribution.

§DOR was defined as the time from the date of either first CR or CRh until the date of a documented relapse of any type.

Deaths were counted as events.

¶Response was ongoing.

XOSPATA Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

The table below summarizes efficacy results by demographic subgroups. These analyses were exploratory and therefore should be interpreted with caution.

Table 3. Subgroup Analyses of Complete Remission Rate by Sex, Race, and Age

Adapted from FDA Review

What are the possible side effects (results of trials used to assess safety)?

The tables below summarize adverse reactions and laboratory abnormalities that occurred in patients from the combined three clinical trials.

Table 4. Adverse Reactions Reported in ≥10% (Any Grade) or ≥5% (Grade 3-5) of Patients with Relapsed or Refractory AML

*Grade 3-5 includes serious, life-threatening and fatal adverse reactions
†Grouped terms: arthralgia, back pain, bone pain, myalgia, musculoskeletal pain, neck pain, non-cardiac chest pain, pain and pain in extremity
‡Grouped terms: aspartate aminotransferase increased, alanine aminotransferase increased, transaminases increased, liver function test increased, hepatic failure, hepatocellular injury and hepatotoxicity
§Grouped terms: blood bilirubin increased and hyperbilirubinemia
¶Grouped terms: asthenia, fatigue and malaise
#Grouped terms: body temperature increased and fever
þGrouped terms: edema, face edema, fluid retention, generalized edema, localized edema, edema peripheral, peripheral swelling and swelling face
ßGrouped terms: diarrhea and diarrhea hemorrhagic
àGrouped terms: aphthous ulcer, mucosal inflammation, mouth hemorrhage, mouth ulceration, oral mucosal blistering, oral mucosal erythema, stomatitis and tongue ulceration
èGrouped terms: hematemesis and vomiting
ðGrouped terms: acute respiratory failure, acute respiratory distress syndrome, dyspnea, dyspnea exertional, hypoxia, pulmonary edema, respiratory distress, respiratory failure, tachypnea and wheezing
øGrouped terms: dermatitis, dermatitis bullous, dermatitis contact, drug eruption, dermatitis exfoliative, eczema asteatotic, lichen planus, erythema, palmar-plantar erythrodysethesia syndrome, photosensitivity reaction, psoriasis, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculo-papular, rash papular, rash pruritic, seborrheic dermatitis, skin exfoliation and toxic skin eruption
ýGrouped terms: pneumonia, lung infection, pneumonia fungal, respiratory syncytial virus infection, respiratory tract infection, lung infiltration, organizing pneumonia, lower respiratory tract infection bacterial, pneumonia aspiration, pneumonitis, interstitial lung disease, lower respiratory tract infection and pneumonia viral
₤Grouped terms: sepsis, bacteremia, septic shock, bacterial sepsis and neutropenic sepsis
¥Grouped terms: blood pressure decreased, hypotension and orthostatic hypotension
ŒGrouped terms: blood pressure increased, hypertension and orthostatic hypertension
ɶGrouped terms: headache and tension headache
ÐGrouped terms: dizziness, dizziness postural and vertigo
AGrouped terms: acute kidney injury, blood creatinine increased, chronic kidney disease, oliguria, renal disorder, renal failure, renal impairment, renal injury and renal tubular necrosis
BGrouped terms: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, epigastric discomfort and gastrointestinal pain

XOSPATA Prescribing Information

Table 5. Most Common (≥20%) New or Worsening Laboratory Abnormalities Reported in Patients with Relapsed or Refractory AML

XOSPATA Prescribing Information

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Tables below summarize adverse events during the clinical trials by sex, age and race subgroups in safety population.

Table 6. Subgroup Analyses of Common Adverse Events by Sex

Table 7. Subgroup Analyses of Common Adverse Events by Race

*Risk difference for Black and White subgroups

Table 8. Subgroup Analyses of Common Adverse Events by Age

FDA Review

Who participated in the trials?

The table below summarizes demographics of all patients in the three clinical trials combined who received XOSPATA at recommended dose (safety population).

Table 9. Baseline Demographics of Patients in the Clinical Trials (safety population)

FDA Review

The table below presents demographics of patients who participated in trial used to establish XOPATA efficacy (efficacy population).

Table 10. Baseline Demographics of Patients in the Clinical Trial 1 (efficacy population)