FDA Investigating Patient Death Following Recombinant ADAMTS13 Therapy

The Food and Drug Administration is investigating the risk of neutralizing antibodies with serious, including life-threatening or fatal, outcomes following treatment with Takeda’s recombinant ADAMTS13 therapy. The investigation follows postmarketing reports of neutralizing antibodies in patients with congenital thrombotic thrombocytopenic purpura (cTTP), including one pediatric death, associated with ADAMTS13, recombinant-krhn.

The fatal case involved a pediatric cTTP patient who developed neurologic symptoms approximately 10 months after starting prophylactic treatment with ADAMTS13, recombinant-krhn, who was later found to have neutralizing antibodies to ADAMTS13. The patient had a prior history of severe allergic reactions to fresh-frozen plasma.

According to FDA, the therapy contains two forms of recombinant ADAMTS13, including a variant that differs from the native sequence by a single amino acid. The agency also noted that current assays cannot distinguish neutralizing antibodies directed at recombinant ADAMTS13 from those targeting endogenous ADAMTS13.

The U.S. prescribing information for ADAMTS13, recombinant-krhn, includes warnings about the potential development of neutralizing antibodies. However, neutralizing antibodies were not reported during clinical trials, and the existing labeling does not reflect these postmarketing cases of serious or fatal outcomes.

Suspected adverse events, including the development of neutralizing antibodies, may be reported to FDA’s MedWatch program.