A phase 3 trial of AstraZeneca’s $800 million rare disease candidate has met its primary endpoint. The update keeps eneboparatide on track to come to market, but the lack of numbers in the readout leave questions about its positioning versus Ascendis Pharma’s Yorvipath unanswered.
AstraZeneca picked up eneboparatide last year in its takeover of Amolyt Pharma. In return for $800 million upfront, plus up to $250 million in milestones, the drugmaker gained ownership of a potential treatment for hypoparathyroidism. People with the thyroid disorder take supplements to restore blood calcium levels and prevent complications such as kidney disease.
Investigators enrolled 202 adults with chronic hypoparathyroidism who were treated with standard of care active vitamin D and oral calcium supplementation. Two-thirds of patients took eneboparatide, a parathyroid hormone (PTH) receptor 1 agonist. The rest received placebo.
After 24 weeks, patients on eneboparatide performed better on the composite primary endpoint. The primary endpoint looked at normalization of albumin-adjusted serum calcium levels and independence from active vitamin D and oral calcium therapy. AstraZeneca said the treatment was well tolerated but provided no further information beyond that brief safety statement and the primary endpoint hit.
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All patients have switched to eneboparatide for an ongoing long-term extension that will monitor safety and efficacy until 52 weeks. Full efficacy and safety data will be analyzed at 52 weeks. Alexion, the rare disease group at AstraZeneca, plans to share the data with global health authorities.
The competitive landscape means the details of the data will matter. Ascendis’ Yorvipath became the first FDA-approved treatment for hypoparathyroidism in adults last year. Jan Mikkelsen, Ascendis’ CEO, was bullish when asked about eneboparatide at the J.P. Morgan Healthcare Conference in January, telling an analyst that “it's hard for me to see it will be better than Yorvipath.”
Mikkelsen believes eneboparatide “can never be a replacement therapy” because it only activates PTH-1. Ascendis sees cognitive benefits to acting on PTH-2 and has flagged the effect of Yorvipath on phosphate as another area in which it may have an advantage.
AstraZeneca, in contrast, has pitched eneboparatide as a potential best-in-class therapy. The drugmaker sees normalizing serum calcium levels, decreasing urinary calcium excretion and preserving bone mineral density as its priorities for the candidate. A belief eneboparatide can deliver those improvements led AstraZeneca to buy Amolyt and include the asset in its road map to $80 billion in annual sales by 2030.