Phase III Lusutrombopag study shows positive efficacy
Shionogi & Co. announced it will present positive efficacy and safety results from a global phase III study (L-PLUS 2) of lusutrombopag (S-888711), an investigational, once-daily, orally administered, small molecule thrombopoietin (TPO) receptor agonist, at the 2017 American Association for the Study of Liver Diseases (AASLD) Liver Meeting to be held October 20-24 in Washington, D.C.
L-PLUS 2 was a multi-national, double-blind, placebo-controlled study conducted in 22 countries to evaluate lusutrombopag for the treatment of thrombocytopenia in patients with chronic liver disease undergoing planned, non-emergent invasive procedures. L-PLUS 2 was the second of two phase III studies of lusutrombopag demonstrating confirmatory data to support the previously reported L-PLUS 1 trial. A total of 215 patients were randomized 1:1 to receive 3mg of lusutrombopag (n=108), or placebo (n=107), up to seven days. Therapy was initiated on Day 1 and invasive procedures were performed between day nine and day 14. A pre-procedure platelet transfusion was mandated by the study protocol if a patient's platelet count prior to the invasive procedure had not reached 50,000/µL.
Key findings from the L-PLUS 2 study will be presented in a late-breaking oral session on Monday, October 23 and include the following:
- Lusutrombopag met the phase III study's primary endpoint, which was defined as the proportion of patients who required no platelet transfusion prior to the procedure and no rescue therapy for bleeding through seven days following the procedure (64.8% of lusutrombopag patients versus 29.0% of placebo patients).
- 8% of patients taking lusutrombopag achieved a platelet count of at least 50,000/µL and had an increase in platelet count of at least 20,000/µL from baseline, compared to 13.1% of patients taking placebo.
- Among patients taking lusutrombopag who required no platelet transfusion (n=74), platelet count of at least 50,000/µL was maintained for a median of 19 days.
- 7% of lusutrombopag patients versus 48.6% of placebo patients experienced adverse events after initiation of study treatment
- Adverse events related to thrombosis were reported in 1.9% of patients in each treatment group. These events included portal vein thrombosis (PVT) which is known as a potential risk in patients with severe chronic liver disease. The L-PLUS 2 study protocol stipulated proactive assessment of thrombosis in the portal vein system by diagnostic imaging devices at the screening and after the invasive procedures (regardless of absence or presence of symptoms of thrombosis). As a result, three PVT events were observed: one patient (0.9%) taking lusutrombopag versus two patients (1.9%) taking placebo. All PVT events were incomplete occlusion therefore considered not clinically significant and resolved with therapy.
- Adverse events related to bleeding occurred in 2.8% of patients in the lusutrombopag group versus 5.6% of patients in the placebo group, respectively. No patients taking lusutrombopag and two patients (1.9%) taking placebo required rescue therapy for bleeding.
- Lusutrombopag was generally well tolerated, with adverse events deemed treatment-related by the investigator in 5.6% of patients taking lusutrombopag versus 12.1% of patients taking placebo.
"There is a clear, unmet need for additional treatment options for our chronic liver disease patients with significant thrombocytopenia, as platelet transfusion is currently their only choice." said Dr. Nezam Afdhal, Director of Hepatology at Beth Israel Deaconess Medical Center and Professor of Medicine at Harvard Medical School. "The safety and efficacy of lusutrombopag may give clinicians an additional option for the treatment of thrombocytopenia in liver disease patients undergoing invasive procedures."
Lusutrombopag has been granted Fast Track designation by the FDA for the treatment of thrombocytopenia in patients with chronic liver disease who are at increased risk for bleeding associated with elective invasive procedures. Shionogi has initiated rolling submission of a New Drug Application to the FDA. Shionogi plans to present L-PLUS 2 study data at the 25th United European Gastroenterology Week in Spain later this month, and at the American Society of Hematology meeting in December.