AstraZeneca called it a success. The adult HPP trial missed its goal—but a subgroup of patients who developed the disease as children did show benefit. The problem: 80 percent of HPP patients are adults.
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AstraZeneca called it a success. The trial data tells a more complicated story.
The drug is efzimfotase alfa — the successor to Strensiq, the Alexion franchise drug that AZ paid $39 billion to acquire. The Phase 3 program enrolled 196 patients across 22 countries in three trials, testing the drug in different HPP populations. The results AZ highlighted in a Monday press release: MULBERRY succeeded, CHESTNUT showed acceptable safety, and HICKORY — the trial that was supposed to open the adult market — missed its primary endpoint. AZ's CEO called it "positive results."
The failure was specific and consequential. HICKORY tested efzimfotase alfa in adolescents and adults with HPP who had not previously received Strensiq. The primary endpoint was the six-minute walk test — a measure of functional exercise capacity — at Week 25. The drug was statistically no better than placebo. AstraZeneca attributed the miss to better-than-expected results in the adult-onset HPP placebo group, which complicates the interpretation but does not change the outcome: the trial failed on its pre-specified primary endpoint in the population AZ needed to reach its $3–5 billion peak sales projection.
The six-times number matters. In February 2025, Alexion CEO Marc Dunoyer said on an earnings call that efzimfotase alfa was designed to reach six times as many patients as Strensiq — which is indicated for perinatal/infantile- and juvenile-onset HPP. Strensiq generated $1.7 billion in 2024. The expansion into adolescents and adults was the growth story. HICKORY was supposed to prove that expansion worked. It did not.
The subgroups tell a different story than the headline. In prespecified subgroups of adolescents and adults who had pediatric-onset HPP — meaning they were diagnosed in childhood but had survived into adulthood — efzimfotase alfa did show nominally statistically significant and clinically meaningful improvements on the 6MWT, as well as secondary endpoints measuring physical function and pain. The open-label extension through Week 48 showed continued improvement. AZ is not wrong to point to these data. But they are not the primary endpoint, and the adult-onset HPP population — the larger commercial opportunity — did not respond on the pre-specified measure.
MULBERRY succeeded clearly. In children ages 2 to under 12 who had not previously received Strensiq, efzimfotase alfa produced statistically significant improvement in bone health compared to placebo at Week 25, as measured by the Radiographic Global Impression of Change score. The trial also hit on rickets severity. This is a meaningful result for a population with limited treatment options. The every-two-weeks subcutaneous dosing — versus Strensiq's three-or-six-times-weekly regimen — matters for adherence in pediatric patients.
CHESTNUT evaluated children switching from Strensiq to efzimfotase alfa. The drug was well-tolerated and maintained the bone health benefit. This is a maintenance result, not a breakthrough, but it matters for the commercial logic: if efzimfotase alfa can sustain Strensiq's benefits with less frequent dosing and lower manufacturing cost — Dunoyer said production costs are "way under" Strensiq — it is a meaningful product line extension even if it does not expand the treated population.
The HPP context is important. Hypophosphatasia is a rare metabolic bone disease caused by insufficient tissue non-specific alkaline phosphatase, leading to defective bone mineralization, rickets, fractures, muscle weakness, and in its most severe infantile form, rapid death. Before Strensiq, there was no specific treatment. Strensiq was the first approved therapy — a recombinant fibroblast growth factor 23 mimetic — and remains the standard of care. Approximately 80% of people living with HPP are adults, according to AstraZeneca, which is why AZ's expansion thesis rested on HICKORY.
The FDA and regulatory path is not yet clear. AZ plans to submit the data to regulatory authorities and present results at a medical meeting. Whether HICKORY's failure changes the risk-benefit calculus for approval depends on whether regulators weight the subgroup data and the open-label extension sufficiently to overlook the missed primary — and whether they view the pediatric data as independently supportive of a broad label. If AZ cannot enter the adolescent and adult market at scale, efzimfotase alfa's commercial future rests on the pediatric and switching indication, where Strensiq already exists and efzimfotase alfa offers dosing convenience and cost advantages.
The Strensiq franchise is the most important thing AZ owns in rare disease. It is also the most vulnerable to generic or biosimilar competition over the next decade. Efzimfotase alfa was supposed to extend that franchise's life. The HICKORY result is a real setback for that plan, regardless of how AZ chose to frame the overall program.
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Research completed — 0 sources registered. Mixed Phase III results for AstraZenecas efzimfotase alfa (ALXN1850) successor to Strensiq. MULBERRY (pediatric, treatment-naïve, n=29): MET primary e
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