Explorer7: Concizumab Reduces Treatment Burden, Preferred by Patients

In the phase 3 explorer7 study (ClinicalTrials.gov Identifier: NCT04083781), researchers compared concizumab to no prophylaxis in patients with hemophilia A or B and inhibitors. 3

This study included 133 male hemophilia patients who were 12 years of age or older. They were randomly assigned to receive no prophylaxis (n=19) or concizumab (n=33), or they were assigned to nonrandomized concizumab arms depending on their pre-enrollment treatment (n=81).

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Previous results from this trial showed that concizumab reduced ABRs and was well tolerated.6 The goal of the current analysis was to determine patient-reported treatment burden and patient preference.3

Patients were instructed to complete the Hemophilia Treatment Experience Measure (Hemo-TEM) questionnaire at baseline and at week 24. Their answers were converted to a score of 0-100 as a measure of treatment burden, with lower scores indicating lower treatment burden.

The mean Hemo-TEM scores showed a significant improvement from baseline to week 24 for patients treated with concizumab (mean estimate -17.0 points; 95% CI, -23.7 to -10.3). No significant improvement in total score was observed for patients not receiving prophylaxis (mean estimate, 3.0 points; 95% CI, -9.4 to 15.3). The estimated treatment difference in total Hemo-TEM scores was statically significant (-19.9 points; 95% CI, -34.3 to -5.6; P =.009).

Patients taking concizumab had improvements in treatment burden across all the Hemo-TEM domains.

Of 99 eligible patients, 77 said they preferred concizumab over their previous treatment. One patient preferred their previous treatment, 16 patients did not respond, and 5 patients indicated no preference.

Reasons patients preferred concizumab included fewer bleeds (75%), shorter treatment time (43%), and concizumab being less painful to inject (33%).

The researchers concluded that subcutaneous concizumab may be a favorable option that is less of a burden for patients with hemophilia A or B and inhibitors.

CHESS II: Data Support Personalized Treatment

The goal of the CHESS II study was to understand the impact of personalized treatment on activity levels and joint health for patients with hemophilia A. 4

The study included 393 adult men with mild (16.3%), moderate (24.9%), or severe (58.8%) hemophilia A. Treatment strategies included primary treatment on demand (35%), no treatment (21%), secondary prophylaxis (20%), primary prophylaxis (19%), and secondary treatment on demand (6%).

There were 147 patients with severe hemophilia A who were receiving prophylaxis. Sixty-seven of them received prophylaxis based on a target trough (TT), and 28 received pharmacokinetic (PK)-guided dosing.

Researchers used 2 forms to assess patients. One was a physician-completed patient record form, and the other was a patient self-completed questionnaire.

The questionnaires showed that patients with severe hemophilia A were less able to be active than patients with mild or moderate disease. The proportion of patients who were unable to be active was 29% in the severe group, 13% in the moderate group, and 17% in the mild group.

Similarly, patients with at least 3 problem joints were less able to be active than patients who had 0 to 2 problem joints. The proportion of patients who were unable to be active was 32% for those with at least 3 problem joints and 24% for those with 0 problem joints.

Patients who received personalized care reported more active hours per month than patients not receiving personalized care — a mean of 13.7 hours and 12.4 hours, respectively. Patients receiving personalized care also reported spending more hours doing sport activities per month — a mean of 7.6 hours and 3.3 hours, respectively.

Patients receiving personalized care had a similar ABR as patients who were not (4.7 and 5.0, respectively).
When compared with patients receiving only TT treatment, patients receiving

PK-guided TT treatment reported more active time per month (mean, 9.0 hours and 24.1 hours, respectively) and a lower ABR (mean, 5.1 and 3.6, respectively), despite having a similar number of problem joints (mean, 0.8 and 1.0, respectively).

Based on these results, the researchers concluded that personalized care may help patients with hemophilia A be more active while maintaining an ideal level of bleed protection.

Disclosures: The HOPE-B trial was supported by uniQure and CSL Behring. The FEIBA STAR study was supported by Baxalta, a subsidiary of Takeda. The explorer7 study was supported by Novo Nordisk A/S. The CHESS II study was supported by Takeda, BioMarin, and Sanofi. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.

References

  1. Pipe SW, Leebeek FW, Recht M, et al. Durability of bleeding protection and factor IX activity in those with and without AA5 neutralising antibodies in the phase 3 HOPE-B clinical trial of etranacogene dezaparvovec for haemophilia B. Presented at: 16th Annual Congress of the EAHAD; February 7-10, 2023. Abstract PO155.
  2. Zülfikar B, Mahlangu J, Nekkal SM, et al. Reduced volume and faster infusion rate of activated prothrombin complex concentrate: A randomized phase 3b/4 trial in adults with hemophilia A or B. Presented at: 16th Annual Congress of the EAHAD; February 7-10, 2023. Abstract PO209.
  3. Hampton K, Knoebl P, Neergaard JS, et al. Treatment burden and patient preference in patients with haemophilia A or B with inhibitors on concizumab prophylaxis: Results from the phase 3 explorer7 study. Presented at: 16th Annual Congress of the EAHAD; February 7-10, 2023. Abstract PO104.
  4. Blenkiron T, Sun SX, O’Hara J, et al. Relationship between physical activity levels and personalized care and clinical outcomes in patients with hemophilia A: Real-world evidence from the CHESS II study. Presented at: 16th Annual Congress of the EAHAD; February 7-10, 2023. Abstract PO052.
  5. Pipe SW, Leebeek FWG, Recht M, et al. Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med. 2023; 388:706-718. doi:10.1056/NEJMoa2211644
  6. Jiménez Yuste V, Angchaisuksiri P, Castaman G, et al. Concizumab prophylaxis in patients with haemophilia A or B with inhibitors: efficacy and safety results from the primary analysis of the phase 3 explorer7 trial. ISTH 2022. July 9-13, 2022. Abstract LB 01.2.

Topics:

Bleeding Disorders Hemophilia