Long-term data support biotech treatment for ITP

Key Points

Recent data suggest that thrombopoietin receptor agonists are safe and effective for the treatment of chronic immune thrombocytopenic purpura, or ITP, over at least 6 years. Long-term data on romiplostim (Nplate, Amgen) showed robust response in approximately 90% of patients compared to 60% to 70% response rates for conventional therapy. Concerns about deposition of reticulin in the bone marrow and resulting bone marrow fibrosis with cytopenia may be overblown.

"This gives clinicians confidence that they can use these agents for a significant length of time with continued efficacy and without major side effects," said David Kluter, MD, head of hematology at Boston's Massachusetts General Hospital. "In the past 4 years, we have not found any new class of side effects," he told Drug Topics. "Bone-marrow reticulation is not even a concern."

Open-label vs. standard of care

The ASH study presented 6 years of open-label study extension data."We presented data on almost 500 patient years of use at ASH," Kluter said. "It basically confirmed what we had published at 2 years and at 4 years. For patients who fail splenectomy, this is the only game in town."

Although ITP has long been referred to as idiopathic thrombocytopenic purpura, it is an autoimmune disorder characterized by thrombocytopenia, which can lead to serious bleeding events, said Michael Newton, assistant professor of clinical pharmacy and clinical specialist, hematology and oncology, West Virginia University School of Pharmacy, Morgantown. Platelet production is intact but platelets are destroyed in the peripheral circulation. The goal of thrombopoietin receptor agonist treatment is to increase platelet production to overcome the patient's immune response.

"ITP is not a common condition by any stretch," Newton said. "There are some very real long-term concerns about the safety of these drugs."

Safety concerns

Concerns include increased risk of venous and arterial clotting, leukemia, antibody formation, and bone-marrow reticulin formation. An oral thrombopoietin receptor agonist, eltrombopag (Promacta, GlaxoSmithKline), also carries a black box warning for hepatotoxicity. As a subcutaneous injection, romiplostim is more difficult to administer but easier to titrate to the desired clinical effect. Both drugs are subject to prescribing and dispensing controls under Risk Evaluation and Mitigation Strategies, or REMS, required by FDA.

As an injectable, romiplostim is typically administered in a hospital or ambulatory care clinic, Newton said. Both prescriber and patient must be registered with NEXUS (Network of Experts Understanding and Supporting Nplate and Patients), the romiplostim REMS program, and the dispenser must maintain an accountability log.

"This could be a drug that is eventually seen in the community," he said. "Once a patient is on a stable dose, there is no reason not to have patients inject themselves. Although the drug is not yet labeled as such, they actually allowed self-injection in these studies."

REMS record-keeping may be a nuisance, but the real barrier to wider romi-plostim use is cost. The typical 20% copay can easily exceed $200 per week, Newton said, although the manufacturer has an active patient-assistance program.

Cost is also an issue for pharmacy. Doses are titrated to effect and can vary from 1 to 10 µg/kg/week. The typical dose is 2 to 5 µg/kg/week, Newton explained, which works out to 150 to 500 µg for most patients. The drug is available in single-use vials of 250 µg or 500 µg. Because the injected amount may be small, it is important to use a syringe with 0.01-mL gradations.

"The important thing is to use the smallest possible vial," he said. "You don't want to give a patient 100 µg out of a 500-µg vial and flush $1,000 down the toilet."