On August 6, 2020, FDA granted accelerated approval to Bayer Healthcare’s
LAMPIT® (nifurtimox) “for the treatment of Chagas disease (American Trypanosomiasis), caused by Trypanosoma cruzi.” Of note: Bayer Healthcare received Orphan designation and a tropical disease priority review voucher. Key findings from the FDA’s
Multidiscipline Review: The applicant provided substantial evidence of effectiveness through
Study 16027 (NCT02625974; n=330), a phase 3, randomized, double-blind clinical trial with a historical control arm.
Intent of the historical control When designing Study 16027, the applicant used a surrogate endpoint to measure effectiveness: change in serologic results or a 20% decrease in optical density. The applicant intended to compare the treatment group to a historical control, using the surrogate endpoint.
Protocols for historical control generation The applicant created a historical control using two published randomized controlled trials:
Sosa Estani (1998) and
De Andrade (1996). The applicant determined a 16% placebo control rate would be appropriate, given the published studies.
Outcome of the historical control submissions FDA concluded that there were limited data supporting the applicant’s selection of a 16% placebo control rate. FDA therefore based its efficacy assessment on a comparison of the randomized treatment arms, instead of the historical control. FDA used the historical control in its assessment of the exploratory endpoint of F29 ELISA serological testing, a “non-conventional” form of serological testing. The reviewer concluded that the historical control provided evidence of effectiveness in the secondary endpoint.
RWE included in the application FDA also provided a prospective and retrospective cohort study,
Fabbro (2007), to support the finding that seroconversion to negative is linked to a lower risk of cardiac abnormalities. The applicant provided post-marketing data to support nifurtimox’s safety profile. For its review of safety, FDA noted that the postmarketing data show a risk of hypersensitivity and skin reactions, as well as thrombocytopenia, which are cited in the label. The label also mentions that postmarketing data do not show a link between nifurtimox and birth defects.
