Longer treatment keeps platelet counts up in ITP, study finds
Wayrilz helps some initial nonresponders sustain higher levels
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Longer treatment with Wayrilz (rilzabrutinib) helped raise and maintain platelet counts in adults with immune thrombocytopenia (ITP), including some who had not achieved a sustained response earlier in treatment.
That’s according to findings from the open-label portion of a Phase 3 LUNA 3 clinical trial (NCT04562766). After an initial period comparing Wayrilz with a placebo, everyone entering this part of the trial received Wayrilz for 28 weeks, including people who had not met response criteria during the first 12 weeks of randomized treatment.
More than one-quarter achieved a durable increase in platelet counts during open-label treatment. Among those who had received Wayrilz but had not achieved a durable response during the randomized period, 12% went on to do so with longer treatment. Longer treatment was also associated with less fatigue and bleeding.
The results provide “extended evidence of the efficacy and safety of rilzabrutinib in [ITP],” the researchers wrote.
The study, “Clinical activity and safety of rilzabrutinib in patients with previously treated immune thrombocytopenia (LUNA3): results from the open-label period of a phase 3 trial,” was published in The Lancet Haematology. It was funded by Sanofi, the company that developed and Wayrilz and is marketing it.
BTK blocker approved in several countries
In ITP, the immune system mistakenly attacks and destroys platelets, the small blood cell fragments needed for clotting, leading to low platelet counts. This can cause easy bruising and prolonged bleeding, along with other ITP symptoms such as fatigue.
Wayrilz is an oral therapy designed to block Bruton’s tyrosine kinase (BTK), an enzyme involved in the activation of immune cells that help drive ITP. By inhibiting these immune cells, the therapy aims to prevent platelets destruction and ultimately control symptoms.
The therapy is approved in the U.S., the European Union, Japan, and other countries for adults with persistent or chronic ITP who have not responded adequately to previous treatments. Regulatory approvals were based on results from the randomized, placebo-controlled portion of LUNA3.
That part of the trial involved 202 adults who had been diagnosed with ITP for more than three months and had either not responded adequately to previous ITP treatments or could not tolerate them. Participants were randomly assigned to Wayrilz at 400 mg or a placebo twice daily for up to 24 weeks.
A durable platelet response was achieved by 31 of 133 people (23%) given Wayrilz and none of 69 given a placebo, meeting the trial’s main goal. Wayrilz also reduced rescue medication use and eased physical fatigue and bleeding, and was well tolerated.
Participants could enter the 28-week open-label period after completing the 24 weeks of the randomized period, or after week 12 if they did not meet predefined response criteria. Everyone then received Wayrilz at 400 mg twice daily.
Study looks at open-label trial participants
In this study, researchers reported results from the 180 adults who entered the open-label period — 115 initially assigned to receive Wayrilz and 65 to a placebo. Participants had been living with ITP for a median of 7.3 years and had received a median of four previous treatments.
During the open-label period, 49 participants (27%) achieved a durable platelet response: 35 of 115 (30%) initially assigned to Wayrilz and 14 of 65 (22%) who switched from the placebo. A durable response was defined as platelet counts of at least 50 billion per liter for at least two-thirds of at least 10 available weekly platelet measurements during the final 16 weeks of the 28-week open-label period, without rescue treatment.
Among the 84 people who had received Wayrilz without achieving a durable response during the randomized period, 10 (12%) did so with continued treatment. The researchers said this suggests that although responses generally occurred quickly, some people may need longer treatment to achieve a durable response
Once achieved, responses were generally maintained: Among durable responders, platelet counts met the study’s response threshold for an average of 88% of the 28 weeks. That threshold was at least 50 billion platelets per liter, or 30 billion to less than 50 billion if the count had at least doubled from baseline (start).
Longer-term data also supported sustained responses. Of 67 participants treated with Wayrilz for at least one year, 36 (54%) achieved a stable response. This meant that after initially responding, their platelet counts did not repeatedly fall below 50 billion per liter without recovering in between during the following 24 weeks. Stable responses lasted a mean of almost 69 weeks, or about 16 months.
Beyond platelet counts, reductions in physical fatigue were maintained or increased during open-label treatment, and bleeding scores also improved. Clinically meaningful gains were seen across several measures of health-related quality of life.
Wayrilz’s safety profile was generally consistent with previous findings, with the most common treatment-related side effects, including nausea and diarrhea, generally being mild or moderate. Four (2%) experienced severe treatment-related side effects, which included hypertension (high blood pressure) and interstitial lung disease. No deaths occurred.
“The emergence of durable responses in patients previously treated with placebo or without initial platelet responses provide additional evidence supporting the activity of [Wayrilz] in patients with [ITP],” the researchers wrote. “These findings reinforce [Wayrilz]’s potential promise as a disease‑modifying treatment option for adults with persistent or chronic [ITP].”
The researchers added that the ongoing long-term extension of LUNA 3 will provide more information about Wayrilz’s long-term activity and safety. A separate Phase 3 study, LUNA 4 (NCT07007962), is also evaluating the therapy in people with ITP who have not responded adequately to previous treatment.
