SYK inhibitors show promise as chronic primary ITP treatment option: Study
Scientists call for more studies to evaluate different medications in this class
Written by |
Spleen tyrosine kinase (SYK) inhibitors, including Tavalisse (fostamatinib disodium hexahydrate), may be effective treatments for adults with chronic primary ITP, however, more studies are needed to evaluate additional medications in this class and compare them with other ITP treatments.
That’s according to a meta-analysis study that assessed the therapeutic potential of SYK inhibitors in ITP. Tavalisse is the only SYK inhibitor currently approved for immune thrombocytopenia (ITP).
“This study suggests that SYK inhibitors may represent a promising therapeutic strategy for patients with chronic primary ITP,” researchers wrote. “Additional large-scale multicenter [randomized controlled trials] are needed to better assess the safety and effectiveness of SYK inhibitors, to evaluate different agents within this class, and to compare SYK inhibitors to other second- or subsequent-line treatments in order to guide clinical decisions and optimize chronic primary ITP management.”
The study, “Spleen tyrosine kinase inhibitors for immune thrombocytopenia: a meta-analysis of randomized controlled trials,” was published in Transfusion and Apheresis Science.
Tavalisse works by blocking key enzyme
ITP is an immune disorder marked by the destruction of platelets, which are small cell fragments that help blood clot. Low platelet levels, medically known as thrombocytopenia, mean that blood cannot clot properly, which can lead to symptoms such as abnormal bruising and bleeding.
Tavalisse is an approved ITP treatment that works by blocking SYK, an enzyme that’s key to the activity of platelet-destroying immune cells. Clinical trials have demonstrated that Tavalisse is superior to a placebo at increasing platelet counts in ITP patients.
Although Tavalisse is currently the only SYK inhibitor approved for ITP, it is not the only medication in this class to have been tested in ITP trials. Another SYK inhibitor, sovlepenib, has also been explored as a potential ITP treatment.
SYK inhibitors more effective a placebo at increasing platelet levels
A team of scientists in Brazil conducted a meta-analysis to evaluate the impact of SYK inhibitors in people with chronic primary ITP. Meta-analysis is a type of study in which researchers pool data from multiple trials and analyze them collectively. This meta-analysis included data from four clinical trials: three that tested Tavalisse and one that tested sovlepenib.
Results broadly showed that both SYK inhibitors were more effective than a placebo at increasing platelet levels.
Statistical analyses showed that patients given SYK inhibitors were more than 17 times more likely to achieve a stable response — defined as platelet counts being at or above 50 billion per liter for at least four of the six scheduled visits in the final months of the trials. The researchers noted that this statistical difference was mainly driven by the fact that almost no one receiving a placebo had a stable response, whereas about one in three patients receiving SYK inhibitors did.
Additional analyses showed that SYK inhibitors consistently outperformed a placebo in patients with severe thrombocytopenia, and that patients receiving SYK inhibitors were less likely to require rescue treatments.
Further investigation of SYK inhibitors, including direct comparisons between different agents and with other second-line therapies, is needed to support the development of evidence-based guidelines and assist decision-making in clinical practice.
Safety data showed that patients given SYK inhibitors were more likely than those given a placebo to experience side effects, particularly hypertension (high blood pressure), but these side effects were generally nonserious and manageable. Rates of bleeding events were not significantly different between patients given SYK inhibitors and those given a placebo.
In addition to collective analyses of the two SYK inhibitors, the researchers also conducted comparisons between Tavalisse and sovlepenib. Their results did not reveal any statistically significant differences — but the researchers stressed that, since this meta-analysis only included one trial on sovlepenib, it’s hard to draw definitive conclusions. As such, the scientists called for further studies to test not only the effects of these therapies but also how they fare against each other.
“Further investigation of SYK inhibitors, including direct comparisons between different agents and with other second-line therapies, is needed to support the development of evidence-based guidelines and assist decision-making in clinical practice,” the researchers wrote.
Tvalisse is sold in the U.S. by Rigel Pharmaceuticals, while sovlepenib is being developed by Hutchmed. Neither company was involved in this study, which was funded by Brazilian health and academic agencies.
