Engineered therapy for blood clotting disorder shows early promise

September 14, 2017
blood
Credit: Wikimedia Commons

An investigational treatment that mimics a key clotting enzyme is effective, safe, and may one day eliminate the need for blood products for people with the rare, life-threatening blood disease hereditary thrombotic thrombocytopenic purpura (TTP), according to a study published online today in Blood, the Journal of the American Society of Hematology (ASH).

Congenital TTP is characterized by blood clots in small blood vessels throughout the body. If untreated, people with TTP can develop strokes, heart attacks, or kidney damage. Today, the most common therapy for TTP consists of plasma infusions, in which individuals with severe cases of the disease must go to a hospital to receive the blood product from a donor to replenish the missing in the blood. However, many patients become intolerant to plasma. They develop severe allergic reactions, which make it nearly impossible to treat them. If they can receive treatment, it's under very close supervision and with precautions.

"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 study author Bruce Ewenstein, MD, PhD, of Shire in Cambridge, MA. "Plasma as a source of enzyme replacement is a sledgehammer approach to 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," he said.

In people with TTP, the plasma levels of an enzyme known as ADAMTS-13 are very low or missing. This important enzyme helps prevent excessive blood clotting in small blood vessels throughout the body. When ADAMTS-13 is absent or deficient, platelet clumping can occur when it shouldn't and cause organ damage. Researchers have created an engineered form of ADAMTS-13 (BAX 930) to restore the missing enzyme in the blood without the potential complications that can result from human-donor plasma or the inconvenience of a hospital visit. Patients could eventually be able to administer their own infusions at home about every two weeks.

In this Phase I, multi-center clinical trial, researchers investigated the safety, tolerability and pharmacokinetics of BAX 930 in 15 patients diagnosed with severe congenital ADAMTS-13 deficiency. Each patient received a single dose of BAX 930. The aim was to determine whether this engineered product increased the missing enzyme, ADAMTS 13, in the body and to determine a safe, effective dose for future studies.

In blood samples from these patients, the researchers found that BAX 930 behaved similarly to the endogenous enzyme and restores ADAMTS-13 activity. Specifically, they observed the normalization of the structure of von Willebrand factor, a protein that works closely with ADAMTS-13 to help regulate platelet function and clotting. They also observed an improvement in platelet counts, which is a marker of TTP disease activity.

Importantly, BAX 930 was well tolerated in all 15 patients, with no allergic reactions or serious adverse events, and no 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 study author Marie Scully, MD, of University College London Hospitals NHS Trust, who is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

A Phase III trial is set to begin later this year. The study will look at the long-term safety and efficacy at both preventing and treating acute attacks. Study participants will be repeatedly exposed 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 have reduced episodes," Dr. Scully said.

Explore further: Doxycycline may cut bleeding with ventricular assist device

Related Stories

Doxycycline may cut bleeding with ventricular assist device

October 13, 2015
(HealthDay)—Doxycycline can potentially cut left ventricular assist device (LVAD)-associated bleeding, according to a study published online Oct. 7 in JACC: Heart Failure.

Engineered clotting protein stops bleeding in most common inherited bleeding disorder

August 3, 2015
The first protein engineered to help control bleeding episodes in patients with severe von Willebrand disease (vW disease) has been shown to be safe and effective, according to results of a Phase III trial. Study data were ...

New treatment option for the acute phase of the rare disease TTP

February 11, 2016
Thrombotic Thrombocytopenic Purpura (TTP) is a rare disorder caused by an enzyme deficiency. This can be heriditary or can be acquired as an autoimmune condition. Due to the associated excessive activity of a certain protein, ...

To treat one rare blood disorder, scientists exploit another

October 27, 2016
For the nearly 400,000 individuals around the world with hemophilia A and hemophilia B—rare blood disorders that impair a person's ability to form clots to stop bleeding—relief may someday come from a treatment with similarities ...

Antibody for severe hemophilia a may reduce injections needed to prevent bleeding

December 1, 2015
An antibody engineered to prevent excessive bleeding in patients with severe hemophilia A may be safe and effective, and require fewer injections than existing options, according to a first-in-human study of the treatment ...

Long lasting anti-hemophilia factor safe in kids

April 24, 2015
Children with hemophilia A require three to four infusions each week to prevent bleeding episodes, chronic pain and joint damage. The effect on quality of life can be significant, due to time and discomfort associated with ...

Recommended for you

Metabolism switch signals end for healing hearts

September 19, 2017
Researchers have identified the process that shuts down the human heart's ability to heal itself, and are now searching for a drug to reverse it.

Beta blockers not needed after heart attack if other medications taken

September 18, 2017
A new study from the University of North Carolina at Chapel Hill finds beta blockers are not needed after a heart attack if heart-attack survivors are taking ACE inhibitors and statins. The study is the first to challenge ...

Which single behavior best prevents high blood pressure?

September 15, 2017
(HealthDay)—You probably already know that certain healthy lifestyle behaviors can reduce your risk of developing high blood pressure, but is any one behavior more important than the others?

RESPECT trial shows closing a small hole in heart may protect against recurrent stroke

September 13, 2017
A device used to close a small hole in the heart may benefit certain stroke patients by providing an extra layer of protection for those facing years of ongoing stroke risk, according to the results of a large clinical trial ...

Study shows so-called 'healthy obesity' is harmful to cardiovascular health

September 11, 2017
Clinicians are being warned not to ignore the increased cardiovascular health risks of those who are classed as either 'healthy obese' or deemed to be 'normal weight' but have metabolic abnormalities such as diabetes.

Statins reduce deaths from heart disease by 28 percent in men with high LDL levels, says longest ever study

September 6, 2017
Previous research has shown the benefit of statins for reducing high cholesterol and heart disease risk amongst different patient populations. However, until now there has been no conclusive evidence from trials for current ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.