NIH study in NEJM shows Novartis drug eltrombopag as first-line therapy with standard treatment improves responses in severe aplastic anemia - Seite 2

"Our research in NEJM shows that eltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed and robustness of hematologic recovery in patients with SAA compared to historical controls," said the study's lead author, Danielle Townsley, MD, researcher in the NHLBI.

In the NIH study, the primary efficacy endpoint of complete response rate with eltrombopag plus standard immunosuppressive treatment at six months exceeded the historic rate (10%) across all three treatment cohorts (cohorts differed in length of eltrombopag administration; dose adjusted by age)[1]. Patients in cohort 1 received eltrombopag from day 14 to six months and achieved a complete response rate of 33%. The complete response was lowest in cohort 2 (26%), in which eltrombopag exposure was shortest (day 14 to three months). Furthermore, overall increases in platelet and neutrophil blood level counts were higher in comparison to the historic cohort, which is a key treatment goal for SAA[1],[4]. The overall survival rate at a median follow-up of two years was 97% (95% CI, 94-100%) for all cohorts[1].

"We are committed to improving the care of people living with serious conditions over the long term, particularly those with few options and great unmet need," said Vasant Narasimhan, Global Head, Drug Development and Chief Medical Officer, Novartis. "Eltrombopag is the  only thrombopoietin receptor agonist to be used in the second-line treatment of SAA, and these results from the NIH study now show its potential as a first-line treatment, which we look forward to discussing with health authorities."

The study also looked at clonal evolution, which is a major complication of SAA (with potential for development of myelodysplastic syndrome and acute myeloid leukemia)[1]. As of May 25, 2016, the addition of eltrombopag did not increase the rate of clonal evolution and was not higher compared to historical data[1],[5],[6],[7]. Clonal cytogenetic evolution occurred in 7 patients at 2 years (95% CI, 1-14%)[1].

The safety profile was consistent with the known safety profile of eltrombopag. Eltrombopag was briefly discontinued during the first two weeks in 7 patients who experienced transient liver enzyme elevations. Two severe adverse events, grade 2-3 cutaneous eruptions, were attributed to eltrombopag and required discontinuation of the drug. Adverse events not attributed to eltrombopag were due to neutropenic infections and known toxicities from immunosuppressive therapy[7]. One death occurred on study in a non-responding patient with thymoma three months following treatment, due to paraneoplastic encephalopathy[1].