Novel Treatment Shows Promise Treating Life-threatening Blood Clotting Disorder

An investigational drug designed to restore missing clotting enzymes in blood was found to be safe and effective in patients with hereditary thrombotic thrombocytopenic purpura (TTP).

When congenital TTP goes untreated, patients can develop strokes, heart attacks, or kidney damage. Standard treatment consists of plasma infusions, but many patients become intolerant to plasma and develop severe allergic reactions.

For patients with TTP, the plasma levels of the enzyme ADAMTS-13 are either very low or nonexistent. ADAMTS-13 helps prevent excessive blood clotting in small blood vessels, but when absent or deficient, platelet clumping can occur and cause damage to organs.

In a study published in Blood, investigators examined a novel treatment that mimics ADAMTS-13, and found it was safe and effective.

“Today, TTP patients are under-treated because of the complications associated with blood plasma infusions, which has remained the standard treatment for at least half a century,” said senior author Bruce Ewenstein, MD, PHD. “Plasma as a source of enzyme replacement is a sledgehammer approach for treatment, but it’s the best we have right now.

“Our novel therapy has the potential to be safer, more convenient, and achieve better outcomes.”

Scientist engineered a form of ADAMTS-13, called BAX 930, to restore the missing enzyme without triggering potential complications. The treatment could eventually eliminate the need for blood products for patients with TTP, and patients could eventually administer their own infusions at home every 2 weeks, according to the study authors.

The multicenter phase 1 clinical trial was designed to examine the safety, tolerability, and pharmacokinetics of BAX 930 in 15 patients with severe congenital ADAMTS-13 deficiency. The goal of the study was to determine whether BAX 930 increased the levels of ADAMTS-13, and whether it was safe and effective.

Each participant was administered a single dose of BAX 930, and the findings showed the drug mimicked the endogenous enzyme and restored ADAMTS-13 activity.

More specifically, the investigators observed the normalization of the blood protein von Willebrand factor; furthermore, there was an improvement in platelet counts.

BAX 930 was well tolerated in all study participants, according to the study. No allergic reactions or serious adverse events were observed, nor were signs of an immune response to the single infusion.

“What the study shows is that this recombinant protein mimics what we would expect the normal protein to do in patients who do not have congenital TTP,” said lead author Marie Scully, MD.

The phase 3 trial is scheduled to begin later this year, and will examine the long-term safety and efficacy in terms of prevention and treatment of acute attacks. The participants will receive repeated infusions to BAX 930 for 12 months.

“This treatment is a complete game-changer for people with TTP, not only for the patients, but also for clinicians to be able to give the right treatment so that patients have reduced episodes,” Dr Scully concluded.