ASH Data Supports Mitapivat as a PK Deficiency Treatment


The results show the mean change from baseline in PKDD was ‒7.19 for M/M patients, ‒4.58 for P/M patients, and ‒3.94 for mitapivat patients.

ASH Data Supports Mitapivat as a PK Deficiency Treatment

Kevin H.M. Kuo, MD, MSc, FRCPC

New data presented at the 2022 American Society of Hematology (ASH) Meeting show the use of mitapivat is beneficial for patients with a pyruvate kinase (PK) deficiency.

PK deficiency is a rare, hereditary hemolytic anemia caused by a single gene defect encoding the red blood cell-specific form of PK. The condition is often associated with acute and long-term complications, as well as a spectrum of signs and symptoms including jaundice, fatigue, and dyspnea.

These symptoms can have a profound, wide-ranging impact on health-related quality of life (HRQoL), where patients report physical limitations, negatively impacted social functioning, reduced self-esteem, and concerns for the future.


One potential treatment option is mitapivat, a first-in-class, oral, allosteric activator of PK.

Through clinical trials, the treatment has resulted in improvement in hemoglobin, hemolysis, and transfusion burden in patients with PK deficiency.

Mitapivat is currently approved by the US Food and Drug Administration for the treatment of hemolytic anemia in adults with PK deficiency.

Studies have also shown improvements in patient-reported outcomes, measured by disease-specific patient-reported outcome instruments--the PK deficiency diary [PKDD] and the PK deficiency impact assessment [PKDIA].

New Data

In the long-term extension study, a team, led by Kevin H.M. Kuo, MD, MSc, FRCPC, Division of Hematology, University of Toronto, the investigators described describe PKDD and PKDIA outcomes up to week 84 in patients with PK deficiency previously enrolled in ACTIVATE and ACTIVATE-T trials.

The ACTIVATE trial is placebo-controlled study in which patients were treated with mitapivat (5/20/50 mg twice daily) or placebo for 24 weeks involving 80 patients.

In the open-label, single-arm ACTIVATE-T trial, 27 patients were treated with mitapivat for 40 weeks.

Patients who completed either trial were eligible to continue in the LTE, where all patients received mitapivat. Patients from ACTIVATE were categorized into either the mitapivat-to-mitapivat arm (M/M) (n = 40) or the placebo-to-mitapivat arm (P/M) (n = 40), while patients from ACTIVATE-T continued to receive mitapivat.

A pair of PK deficiency-specific patient-reported outcomes instruments were used--the PKDD, a 7-item measure of the core signs and symptoms of PK deficiency, and the PKDIA, a 14-item measure of the impacts of PK deficiency on patients' HRQoL.

The investigators assessed, changes from baseline in PKDD and PKDIA mean scores at scheduled visits up to week 84 of the LTE for each of the 3 treatment arms.

For both patient-reported outcome instruments, a lower score represents a lower disease burden, and the minimal clinically important change is defined as a reduction of 4.2 and 5.5 in PKDD and PKDIA scores, respectively.

The results show the mean change from baseline in PKDD was ‒7.19 (6.740) for M/M patients, ‒4.58 (5.758) for P/M patients, and ‒3.94 (14.087) for mitapivat patients.

The mean change from baseline in PKDIA score was ‒6.3 (7.12) for M/M patients, ‒6.3 (9.09) for P/M patients, and ‒11.5 (11.53) for mitapivat patients.

The investigators also found participants in the P/M group experienced improvements in PKDD and PKDIA mean scores after starting mitapivat in the LTE that were consistent with initial improvements seen in the mitapivat-treated group in the ACTIVATE trial. Across both patient-reported outcomes instruments, improvements among mitapivat-treated patients were sustained over time in the LTE.

“Treatment with mitapivat was associated with long-term, durable, and clinically meaningful improvements in signs, symptoms, and functional impacts based on disease-specific PRO instruments, irrespective of transfusion status,” the authors wrote. “These results suggest that by improving HRQoL, treatment with mitapivat may provide meaningful patient-centric benefits.”

The study, “Long-Term Improvements in Patient-Reported Outcomes in Patients with Pyruvate Kinase Deficiency Treated with Mitapivat,” was published online by ASH 2022.

Related Videos
HCPLive Five at ACC 2024 | Image Credit: HCPLive
Ankeet Bhatt, MD, MBA | Credit:
Ankeet Bhatt, MD, MBA | Credit:
Sara Saberi, MD | Credit: University of Michigan
Muthiah Vaduganathan, MD, MPH | Credit: Brigham and Women's Hospital
Veraprapas Kittipibul, MD | Credit:
Addressing HS Risks at the Genetic Level, with Kai Li, BSc
Building a Psoriasis Knockout Regimen Around Risankizumab, with Andrew Blauvelt, MD, MBA
© 2024 MJH Life Sciences

All rights reserved.