AstraZeneca has released detailed results from two phase 3 studies of its investigational enzyme replacement therapy efzimfotase alfa for hypophosphatasia (HPP). The company has not yet disclosed data from a third phase 3 trial, Hickory, which did not meet its primary endpoint.
The data was presented at the International Conference on Children’s Bone Health and expanded on results that AstraZeneca first reported in March. At that time, the company announced that efzimfotase alfa outperformed placebo in the phase 3 Mulberry study, which enrolled treatment-naive children with HPP, a rare disorder that affects bone development. The findings were supported by data from the Chestnut study, which evaluated patients who transitioned from Strensiq to efzimfotase alfa.
In Mulberry, children receiving efzimfotase alfa achieved a median Radiographic Global Impression of Change (RGI-C) score of 1.67 at Week 25, compared with 0 among participants given a placebo. RGI-C is used to assess skeletal health.
A secondary Mulberry endpoint showed a median reduction of 1 point in the Rickets Severity Score (RSS) at Week 25 among patients treated with efzimfotase alfa, while the placebo group showed no change. Rickets, which can occur in people with HPP, is characterized by soft and weakened bones. AstraZeneca additionally reported a nominally significant improvement in physical function and a numerical improvement in performance on the Six-Minute Walk Test (6MWT).
Direct comparisons between Mulberry and studies supporting Strensiq are limited by differences in trial design and patient populations. Mulberry included children between two and 12 years of age. By contrast, evidence supporting Strensiq in juvenile-onset HPP came from a study involving patients aged six to 12 years. For perinatal and infantile-onset HPP, participants ranged in age from three weeks to 39.5 months.
Results from the Chestnut study showed similar rates of treatment-emergent adverse events among participants who switched to efzimfotase alfa and those who remained on Strensiq. Adverse events were reported in 90.5% of patients who transitioned to efzimfotase alfa and in 86.4% of those who continued receiving Strensiq.
Bone health measures remained stable in both the Chestnut study groups. The RGI-C score was 0 in each cohort. RSS results were 0 in the efzimfotase alfa group and -0.08 among patients who stayed on Strensiq.
Administration schedules differ between the two therapies. Patients in Mulberry received efzimfotase alfa through subcutaneous injections every two weeks. Strensiq is administered either three or six times subcutaneously weekly, depending on the prescribed dose.
AstraZeneca’s phase 3 development program was designed to evaluate efzimfotase alfa in a broader population than Strensiq. However, that effort encountered a setback when the Hickory study, which enrolled patients aged 12 years and older who had not previously received Strensiq, failed to demonstrate superiority over placebo on the 6MWT.
Discussing the broader dataset during an April earnings call, Alexion Chief Executive Officer Marc Dunoyer said, “The results show clinically meaningful impact on mobility, physical function, pain, and fatigue that are key aspects of this heterogeneous disease that are beyond one single endpoint such as the 6-minute walk test, the only approved adult endpoint.”
Dunoyer also reiterated expectations that efzimfotase alfa could achieve peak annual sales of between $3 billion and $5 billion. AstraZeneca reported Strensiq sales of $1.7 billion in the previous year.
The company plans to present detailed findings from the Hickory study at an upcoming medical meeting.
Efzimfotase was highlighted by AstraZeneca through new Phase 3 clinical data evaluating its potential as a treatment for pediatric hypophosphatasia (HPP), a rare inherited metabolic bone disease. The latest findings demonstrated encouraging efficacy and safety outcomes, reinforcing the promise of Efzimfotase as a potential therapeutic option for children living with this debilitating condition.
The Phase 3 results represent an important milestone in AstraZeneca’s rare disease portfolio and support ongoing efforts to improve treatment options for patients with hypophosphatasia.
Efzimfotase Shows Promising Clinical Results
The Phase 3 studies found that Efzimfotase produced meaningful improvements across key clinical endpoints in pediatric patients with hypophosphatasia. Researchers assessed measures related to bone health, physical development, mobility, and overall disease progression while also monitoring the therapy’s safety profile.
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