Final trial analysis confirms benefits of approved TTP treatment for all ages
Drug has fewer side effects than blood-based therapy for rare bleeding disorder
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The final results of a now-completed global clinical trial have confirmed that the approved infusion therapy Adzynma (ADAMTS13 recombinant-krhn) prevents acute disease episodes in people with severe congenital thrombotic thrombocytopenic purpura (TTP).
Further, this prophylactic med causes fewer treatment-related side effects than plasma-based therapy among people with the ultra-rare disease, according to the researchers.
These findings come from a late-stage crossover study, launched in 2017, that involved children, teenagers, and adults with the bleeding disorder. Its main goal had been to compare the number of disease events seen among people born with severe TTP when given Adzynma versus standard treatment. Interim data from the Phase 3 clinical trial (NCT03393975) had supported the drug’s approval for both preventive and on-demand treatment of congenital TTP.
Now, a final data analysis concluded that the drug “demonstrated clinical benefits by preventing acute … TTP events and reducing the occurrence of TTP manifestations for patients of all ages.”
The researchers wrote that, “consistent with the interim analysis, results with a longer follow-up support the continued clinical benefit of [Adzynma] prophylaxis in congenital TTP.”
The study, “Recombinant ADAMTS13 in congenital thrombotic thrombocytopenic purpura: final analysis from a randomized phase 3 trial,” was published in the journal Blood. The work was funded by Takeda Pharmaceuticals, the company that markets Adzynma. Nine of the study’s 23 authors are employed by Takeda Development Center Americas.
Congenital TTP is caused by genetic mutations that lead to a severe deficiency of ADAMTS13, an enzyme that helps regulate blood clotting. Without enough ADAMTS13 activity, blood clots form in small vessels, leading to thrombocytopenia, or low levels of platelets — the tiny cell fragments that help blood to clot — and other TTP symptoms. Organs can also be damaged.
Preventive treatment has long relied on plasma-based therapies. Plasma is the noncellular portion of blood that contains several proteins and enzymes, including ADAMTS13. Plasma-based treatments, which typically use fresh frozen plasma (FFP) from healthy donors, are often used to provide the missing enzyme.
While generally effective, these treatments deliver variable amounts of ADAMTS13 and require large, lengthy infusions that can cause allergic reactions.
Adzynma has been approved in US since 2023
Adzynma is an enzyme replacement therapy that delivers a lab-made, functional version of ADAMTS13 to the body. Administered intravenously, or directly into the bloodstream, it was approved for congenital TTP in the U.S. in 2023 and in Europe in 2024.
This Phase 3 trial, which led to those approvals, enrolled people ages 3 to 68 with congenital TTP, defined by ADAMTS13 activity below 10%. It aimed to evaluate Adzynma’s safety and effectiveness for both preventive and on-demand treatment.
The on-demand group comprised five participants who received Adzynma or plasma-based therapy to treat an acute TTP event. Three later entered the preventive-treatment group, which involved 48 participants randomly assigned to intravenous, or into-the-vein, Adzynma at 40 international units per kilogram (IU/kg), or plasma-based therapy. Treatment was given once weekly or every two weeks.
After six months, the participants switched treatments for another six months, after which all received Adzynma for an additional six months.
At the interim analysis, 32 participants — all adults or adolescents — had completed the trial. Effectiveness findings showed no acute TTP events during Adzynma prophylaxis versus one during plasma-based therapy. Additionally, the data showed fewer TTP symptoms and substantially higher ADAMTS13 activity with Adzynma.
Safety data, available from all 48 participants, also showed fewer treatment-related side effects with Adzynma than with plasma-based therapy.
Patients rank therapy higher for convenience, effectiveness
The researchers have now reported the final results from the completed trial, extending the effectiveness analysis to all age groups, including children younger than 12.
In line with the interim findings, no acute TTP events occurred during Adzynma prophylaxis, while one event, triggered by a viral infection, occurred during plasma-based therapy.
Less severe, or subacute, TTP events were also less frequent with Adzynma, although the difference was not statistically significant, the team reported.
Thrombocytopenia also occurred less often with Adzynma, with estimated annualized rates of 0.91 versus 1.62. Neurological symptoms, abdominal pain, and elevated lactate dehydrogenase (LDH), a marker of tissue damage, also tended to occur less often with Adzynma.
Findings in children showed a similar pattern, the researchers noted, with no acute TTP events during Adzynma prophylaxis and fewer subacute events and other TTP manifestations than with plasma-based therapy. However, only eight participants were younger than 12, limiting conclusions for this age group, the researchers noted.
Adzynma also continued to show a more favorable safety profile than standard treatment. Therapy-related side effects occurred in 4% of participants with Adzynma versus 46% with plasma-based therapy. No serious side effects were considered related to Adzynma, while one serious case of fever was linked to plasma-based therapy, the team noted.
No hypersensitivity, or allergic, reactions occurred during Adzynma prophylaxis, compared with 24 hypersensitivity-related events during plasma-based therapy. With plasma therapies, such events occurred for 12 participants despite medications given beforehand to help prevent such reactions.
Adzynma was also much faster to administer, with infusions lasting a median of about five minutes versus about 132 minutes, or more than two hours, for plasma-based therapy, the team noted.
Collectively, these findings reinforce [Adzynma] prophylaxis as a practical long-term management option for [congenital TTP] patients of all ages.
Among adults who completed treatment-satisfaction questionnaires, Adzynma was rated more favorably for convenience, effectiveness, and overall satisfaction, the researchers reported.
Adzynma also produced greater and more sustained ADAMTS13 activity. Activity was about six times higher with Adzynma than with plasma-based therapy and remained at or above 10% for longer, with similar patterns across age groups, the researchers noted.
No ADAMTS13-neutralizing antibodies were detected in participants with confirmed congenital TTP during the trial. Since then, however, and after Adzynma’s approval, neutralizing antibodies have been reported, including serious outcomes. That prompted a boxed warning in the U.S. prescribing information about the risk.
“Collectively, these findings reinforce [Adzynma] prophylaxis as a practical long-term management option for [congenital TTP] patients of all ages,” the researchers wrote.
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