FDA Investigates Patient Death Linked to Takeda's Enzyme Replacement Therapy Adzynma

The U.S. Food and Drug Administration (FDA) has launched an investigation into Takeda's recombinant protein medication Adzynma following reports of adverse events, including one patient death. The probe focuses on the development of neutralizing antibodies in patients treated with the enzyme replacement therapy for congenital thrombotic thrombocytopenic purpura (cTTP).

Patient Death and Neutralizing Antibodies

The FDA reported that a pediatric cTTP patient died after receiving treatment with Adzynma. The patient, who had previously experienced severe allergic reactions to fresh frozen plasma, developed progressive neurological symptoms approximately 10 months after starting Adzynma treatment. Tests revealed the presence of anti-ADAMTS13 antibodies.

The regulator stated that the death "appears to be related to Adzynma," noting that current assays cannot differentiate between antibodies produced against the recombinant enzyme and those targeting the endogenous protein. This limitation complicates the assessment of the antibody response's origin.

Takeda, however, maintains that their thorough assessment found "no confirmed causal relationship" between Adzynma use and the patient death. A company spokesperson emphasized that the "health and safety of the patients we serve is our top priority" and stated that Takeda had been keeping the FDA informed since becoming aware of the situation in July.

Adzynma: First Approved Enzyme Replacement Therapy for cTTP

Adzynma, approved by the FDA in November 2023, is the first recombinant protein product for preventive or on-demand enzyme replacement therapy in adults and children with cTTP. The rare genetic blood-clotting disorder affects fewer than 1 in 1,000 people and results from mutations in the ADAMTS13 gene, which produces an enzyme crucial for regulating blood clotting.

The medication contains two versions of recombinant ADAMTS13: a native sequence and a variant sequence differing by a single amino acid. Its current U.S. label includes information about the potential risk of patients developing neutralizing antibodies following treatment but does not mention postmarketing reports of such antibodies associated with serious or fatal outcomes.

FDA's Ongoing Safety Evaluations

This investigation into Adzynma follows two other high-profile safety probes conducted by the FDA over the past year. In December, the agency investigated reports of patients developing blood cancer after receiving bluebird bio's gene therapy Skysona, leading to restricted use of the treatment. More recently, the FDA examined two patient deaths linked to Sarepta Therapeutics' gene therapy Elevidys for Duchenne muscular dystrophy, resulting in label limitations.

As the investigation unfolds, the FDA continues to evaluate the need for further regulatory action regarding Adzynma. The agency advises patients to consult their healthcare providers about monitoring potential inhibitors to ADAMTS13 through blood testing.