AstraZeneca's $1.05 Billion Bet Pays Off: Eneboparatide Hits Primary Endpoint in Phase III CALYPSO Trial

On March 17, AstraZeneca announced positive results from the Phase III CALYPSO study of eneboparatide, a parathyroid hormone (PTH) receptor 1 agonist. The CALYPSO study is the first Phase III clinical trial in which the drug has met its primary endpoint, validating its clinical benefits. The study results showed that at 24 weeks, eneboparatide achieved the primary endpoint with statistical significance in adult patients with HypoPT.

Eneboparatide was acquired by AstraZeneca for $1.05 billion in March 2024 when it was in Phase III clinical development.

On the same day, AstraZeneca also announced two other deals: the $1 billion acquisition of Belgian biotech company EsoBiotec to enter the CGT field, and a collaboration with South Korean biotech company Alteogen worth up to $1.35 billion. The positive results of the CALYPSO study further demonstrate AstraZeneca's sharp strategic vision in business development (BD).

Eneboparatide is a parathyroid hormone (PTH) receptor 1 agonist indicated for hypoparathyroidism. Its mechanism of action involves high-affinity binding to a specific conformation of the parathyroid hormone receptor 1, mimicking the effects of parathyroid hormone. As hypoparathyroidism results from PTH deficiency leading to impaired regulation of calcium and phosphorus levels in the blood, eneboparatide, as a PTH replacement, helps regulate calcium-phosphorus balance, thereby treating hypoparathyroidism.

Hypoparathyroidism is a rare endocrine disorder caused by PTH deficiency, characterized by impaired regulation of calcium and phosphorus levels in the blood, which can lead to negative effects on the kidneys and bones. Relevant data shows that the disease affects more than 200,000 people in the United States and the European Union, with approximately 80% being female. Current mainstream clinical treatments include active vitamin D and oral calcium supplements.

The global, randomized, double-blind, placebo-controlled, multicenter CALYPSO study showed that eneboparatide reached the primary endpoint with statistical significance and was well-tolerated in adult patients with hypoparathyroidism. After the 24-week primary treatment period, all patients were extended to receive eneboparatide treatment until 52 weeks. The complete efficacy and safety data will be analyzed at 52 weeks.

The first representative drug of PTH replacement therapy approved globally is YORVIPATH®, developed by the Danish pharmaceutical company Ascendis Pharma A/S — approved in the EU in November 2023, in the U.S. in August 2024, and in Australia on February 21, 2025. This is the first drug listed in the Australian Register of Therapeutic Goods for the treatment of chronic hypoparathyroidism, a first-of-its-kind PTH replacement therapy. As a prodrug of parathyroid hormone (PTH (1 - 34)), it is administered once daily via subcutaneous injection, with a sustained-release design that provides physiological levels of PTH over 24 hours. Its approval was supported by the results of Ascendis Pharma's Phase 3 PaTHway trial, which demonstrated the efficacy, safety, and tolerability of YORVIPATH as a once-daily PTH replacement therapy.

In November 2018, Ascendis announced the establishment of VISEN Pharmaceuticals through a joint venture with a group of investors led by Vivo Capital. VISEN Pharmaceuticals has the exclusive rights to develop, manufacture, and commercialize YORVIPATH in Greater China.

In addition, innovative therapies for hypoparathyroidism mainly focus on PTH1R and the vitamin D receptor, with ongoing exploration of new treatment methods and drugs to provide more effective therapeutic options for patients.

According to AstraZeneca's 2023 financial report, its global rare disease business revenue reached $7.764 billion, already becoming the company's third-largest business pillar.

Entering 2024, the momentum of performance growth has become even stronger. Taking the second-generation C5 monoclonal antibody Ultomiris (Ravulizumab) as an example, its sales have been advancing rapidly, with annual revenue climbing to $3.924 billion, representing a growth rate of 34%. It has successfully surpassed the first-generation drug Soliris (Eculizumab), smoothly completing the product iteration transition. The neurofibroma drug Koselugo (Selumetinib) also delivered impressive results, achieving $631 million in sales in 2024, marking a year-on-year increase of 96%. Additionally, Strensiq (Asfotase Alfa) and Kanuma (Sebelipase Alfa), two innovative enzyme replacement therapies, contributed $1.625 billion in revenue to the company, demonstrating strong market competitiveness.

Looking back at 2021, AstraZeneca invested heavily in the acquisition of Alexion Pharmaceuticals, officially entering the rare disease field. In the same September, AstraZeneca swiftly established its Rare Disease Division in China. Since then, AstraZeneca has been increasing its resource investment and strategic layout in the rare disease sector year by year. In the first half of 2023, Alexion's rare disease business generated $3.919 billion in revenue for AstraZeneca, marking a 12% year-on-year increase. With Alexion’s over 30 years of profound expertise and leading advantages in the rare disease field, by the end of 2023, AstraZeneca had received approval for five innovative rare disease drugs globally, covering seven indications, including Eculizumab, Ravulizumab, Strensiq (asfotase alfa), Kanuma (sebelipase alfa), and Coseela. Currently, AstraZeneca’s global rare disease R&D pipeline is robust, comprising more than 20 projects, including 11 novel molecular entities. In 2022, AstraZeneca acquired LogicBio Therapeutics, a clinical-stage genetic company, dedicated to developing new gene therapies for children with rare diseases. In July 2023, AstraZeneca entered into a collaboration agreement with Pfizer to jointly advance the development of next-generation genomic medicines, aiming to expand complementary pipeline assets and explore innovative technologies together.

Focusing on the Chinese market, AstraZeneca China's Rare Disease Division has successfully introduced two innovative drugs, covering five indications. In the new version of the "National Basic Medical Insurance, Work-related Injury Insurance, and Maternity Insurance Drug Catalog (2023)" to be implemented from 2025, several of AstraZeneca's rare disease drugs are prominently listed. These drugs can be used to treat paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) in adults and children, refractory generalized myasthenia gravis (gMG) in adults who are positive for anti-acetylcholine receptor (AChR) antibodies, as well as type I neurofibromatosis (NF1) in pediatric patients aged 3 years and above with symptomatic and inoperable plexiform neurofibromas (PN).

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"Focusing on Building the Ecosystem for Rare Disease Diagnosis and Treatment! AstraZeneca Continues to Demonstrate Global Leadership" Pharmaceutical Economy News