PTH1R

Amolyt Pharma’s phase 3 study is assessing whether eneboparatide can free patients from the need to take supplements. AstraZeneca is paying $800 million to expand into rare endocrinology, snagging itself a phase 3 candidate through the acquisition of French biotech Amolyt Pharma. The deal features $250 million in milestones tied to a regulatory event. Buying Amolyt will give AstraZeneca control of eneboparatide, a PTHR1 agonist that the biotech moved into phase 3 in June. Eneboparatide is designed to produce sustained and stable levels of calcium, which falls to low levels in patients with hypoparathyroidism, while preventing kidney disease and restoring bone turnover.  People with the thyroid disease take supplements to restore blood calcium levels, often for life. Amolyt’s phase 3 study is assessing whether eneboparatide can free patients from the need to take vitamin D and oral calcium. If the molecule can give patients that freedom and keep serum calcium in the normal range, the study could meet its primary endpoint and position AstraZeneca to file for approval. Marc Dunoyer, CEO of AstraZeneca’s rare disease unit Alexion, said in a statement that eneboparatide has the “potential to lessen the often debilitating impact of low parathyroid hormone and avoid the risks of high-dose calcium supplementation.” AstraZeneca’s move to address that need is part of a push into a new therapeutic area.  “Chronic hypoparathyroid patients face a significant need for an alternative to current supportive therapies, which do not address the underlying hormone deficiency,” Dunoyer said. “We believe this program, together with Amolyt’s talented team, expertise and earlier pipeline, will enable our expansion into rare endocrinology.” The FDA approved NPS Pharmaceuticals’ Natpara, which is now sold by Takeda, in hypoparathyroidism in 2015, but manufacturing problems have blighted the product. Takeda recalled batches from the U.S. in 2019 and, after the timeline for returning to the market slipped, decided to give up altogether in 2022. The drugmaker plans to stop manufacturing the drug globally by the end of the year.

AstraZeneca will acquire Amolyt Pharma, a clinical-stage biotech company specializing in the development of treatments for rare endocrine disorders. The move, executed through Alexion, AstraZeneca Rare Disease, will further strengthen the drugmaker's late-stage pipeline in rare endocrine disease through the acquisition of eneboparatide (AZP-3601), a phase 3 therapeutic peptide. Eneboparatide, designed to treat hypoparathyroidism, binds selectively to the parathyroid hormone receptor, regulates serum calcium levels, reduce urinary calcium excretion, and potentially prevent kidney function decline and chronic kidney disease. Amolyt's pipeline also includes AZP-3813, a phase 1 peptide growth hormone receptor antagonist for the potential treatment of acromegaly, a disorder that occurs when the body makes too much growth hormone. AstraZeneca will acquire all outstanding shares of France-based Amolyt for up to $1.05 billion, including an $800 million upfront payment and an additional $250 million contingent upon regulatory milestones. The transaction, pending customary closing conditions and regulatory approvals, is slated for completion by the end of the third quarter of 2024. Since the creation of its Rare Disease unit following the $39 billion takeover of Alexion Pharmaceuticals in 2021, AstraZeneca has continued to snatch up rare disease drugmakers, picking up New Jersey-based Caelum Biosciences in September 2021 and Massachusetts-based LogicBio Therapeutics in October 2022 .

AstraZeneca’s rare disease portfolio generated $7.76bn in global sales in 2023, as per the company’s Q4 financials. Image Credit: EllaSt / Shutterstock. AstraZeneca has signed a definitive agreement to acquire Amolyt Pharma, which specialises in therapies for rare endocrine diseases, in a deal worth $1.05bn. As per the contract, AstraZeneca will pay $800m upfront along with potential regulatory milestone payments of $250m. The deal is expected to close in Q3 2024. Amolyt’s lead candidate, eneboparatide (AZP-3601), was a central part of the acquisition. Eneboparatide is a subcutaneous parathyroid hormone receptor 1 (PTHR1) agonist for the treatment of hypoparathyroidism. This condition is caused by a deficiency in the parathyroid hormone that results in decreased calcium and elevated phosphorus levels in the blood. Dysregulation of parathyroid hormone can lead to osteoporosis and chronic kidney disease. Amolyt launched a Phase III CALYPSO trial (NCT05778071) for eneboparatide in May 2023. Topline data from the trial is expected by the end of this year. Another candidate in Amolyt’s pipeline is AZP-3813. The therapy is a peptide growth hormone receptor antagonist, which is being developed as a potential add-on to somatostatin analogues for the treatment of acromegaly, a condition associated with abnormally high secretion of growth hormone. It can lead to a variety of complications including heart failure and impaired glucose tolerance. The company initiated a Phase I trial for AZP-3813 in June 2023. See Also: Almirall to license Eloxx’s ZKN-013 for rare skin conditions Risk adjusted net present value: What is the current valuation of AstraZeneca’s AZD-3427? AstraZeneca’s rare disease portfolio generated $7.76bn in global sales in 2023, as per the company’s Q4 financials. The UK pharma giant has been investing heavily in rare disease therapies starting with the $39bn acquisition of Alexion in 2021. Last year, the company paid $1bn to acquire an early-stage gene therapy portfolio for rare diseases from Pfizer. According to a GlobalData report, innovation in rare diseases is seen as a risky investment, with rare oncology indications dominating most of the rare disease pipeline. GlobalData is the parent company of Pharmaceutical Technology . Despite this, AstraZeneca has seen some success amongst rare diseases that are not cancer-related. In September 2023, the Phase III trial for a rare vasculitis therapy, Fasenra (benralizumab), met its primary endpoint. The study found that Fasenra was non-inferior to the current standard of care, Pfizer’s Nucala (mepolizumab). Earlier this year, AstraZeneca reported positive outcomes from its Japan Phase III clinical trial of acoramidis, an investigational treatment for a rare cardiomyopathy, transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).