The FDA has opened an investigation into Takeda’s recombinant protein med Adzynma following the reported death of a pediatric patient who received the drug.
The probe comes as the regulator says it has received multiple postmarketing reports of patients developing neutralizing antibodies to ADAMTS13, the enzyme-creating gene that underpins Takeda’s drug. The single reported patient death “appears to be related to Adzynma,” the FDA said in a Nov. 21 safety communication.
Takeda’s medicine was approved in November of 2023 as the first recombinant protein product for use as a preventive or on-demand enzyme replacement therapy in adults and children with the rare genetic blood-clotting disorder, congenital thrombotic thrombocytopenic purpura (cTTP). The condition is believed to be caused by a disease-triggering mutation in the ADAMTS13 gene, which produces an enzyme responsible for regulating clotting.
"The health and safety of the patients we serve is our top priority and we are saddened by the death of this patient," a Takeda spokesperson told Fierce Pharma in an emailed statement. The company reported the event to the FDA and has been keeping the agency apprised since it became aware of the situation in July, the spokesperson explained.
"We have also conducted a thorough assessment and determined that there was no confirmed causal relationship to the use of Adzynma (ADAMTS13, recombinant-krhn) and the patient death," the spokesperson continued.
The company representative added that "[t]here are no changes to the overall risk/benefit profile of Adzynma at this time."
Regarding the pediatric death, the patient had severe allergic reactions to fresh frozen plasma prior to Adzynma treatment, the FDA said in its Friday announcement, laying the case for why it believes Takeda’s treatment is connected.
The patient presented neurologic symptoms, which the FDA said “progressed.” Ultimately, neutralizing antibodies to ADAMTS13 were identified in the patient some 10 months after starting prophylactic treatment with Adzynma, per the regulator.
The FDA caveated that current assays can’t distinguish between neutralizing antibodies to recombinant ADAMTS13—the core ingredient of Takeda’s drug—and those targeting the endogenous form of the gene.
Adzynma contains two versions of recombinant ADAMTS13: a native sequence and a variant sequence that differs from the first by “a single amino acid,” according to the FDA.
The drug’s U.S. label already includes information noting the potential risk that patients may develop neutralizing antibodies following Adzynma treatment. As it stands, patients are advised to talk to their healthcare providers about monitoring potential inhibitors to ADAMTS13 via blood testing.
Under Adzynma’s current U.S. approval, the drug’s label does not include information highlighting “postmarketing reports of neutralizing antibodies associated with serious, including fatal, outcomes,” the FDA pointed out.
The agency’s investigation into Abzynma follows two other high-profile safety probes over the past year.
Last December, the FDA said it was eyeing “further regulatory action” as it launched an investigation into reports of patients developing blood cancer after receiving bluebird bio’s cerebral adrenoleukodystrophy gene therapy Skysona (Bluebird bio recently rebranded as Genetix Biotherapeutics.)
In August, the FDA formally restricted Skysona, updating the gene therapy’s indication to cover use exclusively in patients who do not have an available human leukocyte antigen (HLA)-matched donor for stem cell transplant. The FDA ultimately ruled that Skysona shouldn’t be used in patients with treatment alternatives, given the concerns around an increased risk of blood cancer.
Notably, the FDA also kicked off an investigation this summer into a pair of Duchenne muscular dystrophy (DMD) patient deaths following treatment with Sarepta Therapeutics’ gene therapy Elevidys.
“FDA is investigating the risk of acute liver failure with serious outcomes, including those such as hospitalization and death, following Elevidys, and is evaluating the need for further regulatory action,” the regulator said at the time.
The incident proved contentious and also marked a test of new leadership at the FDA, with controversial CBER chief Vinay Prasad, M.D., briefly departing—and then returning to his post—in the aftermath of a tug-of-war between Sarepta and the regulator over its gene therapy.
Last week, the FDA officially limited Elevidys’ label, restricting access to the gene therapy for DMD patients who are no longer able to walk independently. Further, the drug’s label now only covers ambulatory DMD patients who are at least 4 years of age.
Editor's note: This story was updated at 4:20 p.m. ET on Nov. 11 to include a statement from Takeda.