FIRST AND ONLY TREATMENT FOR CHRONIC HYPOPARATHYROIDISM APPROVED IN AUSTRALIA

• YORVIPATH^® (palopegteriparatide) is now registered by the Therapeutic Goods Administration (TGA) for the treatment of chronic hypoparathyroidism in adults¹
• First-in-class novel PTH replacement therapy
• Australia becomes the first country to obtain Marketing Authorisation for YORVIPATH since FDA approval

SINGAPORE, Feb. 21, 2025 /PRNewswire/ -- Independent biopharmaceutical company Specialised Therapeutics (ST) welcomes the registration of YORVIPATH^® (palopegteriparatide) by the Therapeutic Goods Administration (TGA), "for the treatment of chronic hypoparathyroidism in adults".^1,2 YORVIPATH was granted an Orphan Drug Designation and assessed through the TGA's Priority Review pathway.^3,4 It is the first and only medicine to be listed on the Australian Register of Therapeutic Goods (ARTG) for the treatment of chronic hypoparathyroidism.

Hypoparathyroidism is a rare, complex endocrine disease, affecting an estimated 6.4-37 per 100,000 people globally.^5,6 It is an endocrine disorder in which the production of parathyroid hormone (PTH) by the parathyroid glands is abnormally low or absent, causing low levels of calcium (hypocalcaemia) and high levels of phosphorous (hyperphosphataemia) in the blood.^7,8 This impacts proper functioning of nerves and muscles, leading to weakness, muscle spasms or cramps, headaches, hair loss, numbness or tingling, and memory problems.^8,9 Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extraskeletal calcifications, and cognitive impairment.¹⁰

Leading Australian Endocrinologist and Head of the School of Clinical Sciences at Monash Health, Professor Peter Ebeling AO, applauded the TGA approval of YORVIPATH in addressing an unmet medical need for Australian adults diagnosed with chronic hypoparathyroidism.

"Until now, the only treatment option for adults with chronic hypoparathyroidism has been conventional therapy with calcium and active vitamin D supplementation to keep blood calcium levels normal," said Professor Ebeling. "While these treatments help to manage the symptoms of hypoparathyroidism, they do not address the underlying deficiency of PTH and contribute to the significant pill burden for patients."

"The lack of effective therapeutic options has been an urgent medical need in this area, and the local approval of YORVIPATH represents an important advance in the treatment of chronic hypoparathyroidism in Australia," said Professor Ebeling. 

YORVIPATH is a first-in-class PTH replacement therapy. A prodrug of parathyroid hormone (PTH [1-34]), YORVIPATH is administered subcutaneously once daily, with sustained release of active PTH designed to provide PTH levels in the physiological range for 24 hours/day.¹¹

YORVIPATH's approval in Australia was supported by the results of Ascendis Pharma's Phase 3 PaTHway trial, a 26-week randomised, double-blind, placebo-controlled study with a 156-week open-label extension, published in the Journal of Bone and Mineral Research.¹² Involving 84 adults with chronic hypoparathyroidism, the clinical trial demonstrated the efficacy, safety and tolerability of YORVIPATH as a once-daily PTH replacement therapy.

Data from the pivotal trial showed 93% (57/61) of YORVIPATH-treated patients achieved independence from both active vitamin D and therapeutic doses of elemental calcium, which was associated with a clinically meaningful reduction in their daily pill burden.¹²

The safety analysis demonstrated YORVIPATH was generally well-tolerated, with the most frequently reported adverse reactions being injection site reactions (21.6%), headache (18.7%), and paraesthesia (13.7%).²

In addition to the significant short-term and long-term medical complications of chronic hypoparathyroidism, individuals diagnosed with the condition also experience reduced health-related quality of life, including the negative impact of symptoms on their daily life and work productivity.¹²

Chief Executive Officer of the Australian Thyroid Foundation (ATF), Beverley Garside, acknowledged the significance of the TGA approval in offering adults living with chronic hypoparathyroidism the opportunity to improve their health and wellbeing. However, she reinforced that this is not the time for complacency, as it is just the first step towards securing subsidised access to an important new treatment option for this community.

"As the leading national voice for good thyroid health in Australia, the ATF recognises the importance of the TGA registration of YORVIPATH as a new treatment option for the hypoparathyroid community. While this is positive news, it is only the first step," said Ms Garside. "For adults diagnosed with chronic hypoparathyroidism to truly benefit from this new treatment, it is essential they have the option of subsidised and affordable access to YORVIPATH through the Pharmaceutical Benefits Scheme as quickly as possible."

YORVIPATH is being made available in Australia by Specialised Therapeutics (ST), under an exclusive distribution agreement with global biopharmaceutical company Ascendis Pharma A/S that covers Australia, New Zealand, Singapore, Malaysia, Brunei, Thailand, and Vietnam. The Australian registration of YORVIPATH follows approvals issued to Ascendis Pharma by the United States Food and Drug Administration (US FDA)¹³ in August 2024 and the European Medicines Agency (EMA)¹⁴ in November 2023.

"The Australian approval of YORVIPATH reflects our values and dedication to applying science to help address the significant unmet medical needs expressed by the hypoparathyroidism community," said Roy Khoury, Vice President, Head of International Markets at Ascendis Pharma. "We are pleased to partner with Specialised Therapeutics to broaden access to this innovative therapy, based on our TransCon technology, which offers a new approach to the treatment of this often-debilitating rare disease."

ST Chief Executive Officer, Mr Carlo Montagner, said the approval of YORVIPATH was a meaningful milestone, but the company would not stop until it achieved reimbursement for eligible Australians with hypoparathyroidism through the Pharmaceutical Benefits Scheme (PBS).

"We are proud to have brought the first and only TGA-registered treatment for chronic hypoparathyroidism to Australians living with the condition so rapidly following the recent FDA and EMA approvals," said Mr Montagner. "Chronic hypoparathyroidism has considerable and life-long wide-ranging impacts on these individuals and we are committed to working with the local hypoparathyroidism community and the Australian Government to ensure YORVIPATH is accessible to eligible patients through the PBS at the earliest opportunity."

YORVIPATH will be reviewed by the Pharmaceutical Benefits Advisory Committee (PBAC) at its first meeting of the year, to be held from 12-14 March 2025. YORVIPATH will be made available for prescribing in Australia once it has been listed on the PBS.

About Specialised Therapeutics

Founded in 2007, Specialised Therapeutics is the region's largest independent specialty pharmaceutical company, providing new therapies and technologies to patients in Australia, New Zealand and across Southeast Asia. Headquartered in Singapore, ST partners with global pharmaceutical, biotech and diagnostic companies to bring novel healthcare opportunities to patients who are impacted by a range of diseases. ST has built a strong track record of success, navigating complex regulatory, reimbursement and commercialisation environments in its diverse regions. The ST mission is to provide specialty therapies where there is an unmet need. The company's broad therapeutic portfolio currently includes novel agents in oncology, haematology, CNS, neurology, endocrinology, ophthalmology and supportive care, although it is not confined to these areas. ST is a member of the World Orphan Drug Alliance (WODA).

Additional information can be found at www.stbiopharma.com

About Ascendis Pharma

Ascendis Pharma is applying its innovative TransCon technology platform to build a leading, fully integrated biopharma company focused on making a meaningful difference in patients' lives. Guided by its core values of patients, science and passion, the company uses its TransCon technologies to create new and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Europe and the United States. Please visit: ascendispharma.com to learn more.

About Hypoparathyroidism¹⁰

Hypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH), the primary regulator of calcium and phosphate balance in the body, acting directly on bone and kidneys and indirectly on the intestines. Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extra-skeletal calcifications, and cognitive impairment. Post-surgical hypoparathyroidism accounts for the majority of cases (70-80%), while other etiologies include autoimmune and idiopathic causes.

About PaTHway¹²

The PaTHway trial was a double-blind, placebo-controlled, 26-week, Phase 3 study that assessed the efficacy and safety of PTH replacement therapy with palopegteriparatide for individuals with hypoparathyroidism. Participants (n=84) were randomised 3:1 to once-daily palopegteriparatide (initially 18 μg/d) or placebo, both co-administered with conventional therapy.

The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3–10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. At week 26, 79% (48/61) of participants treated with palopegteriparatide versus 5% (1/21) with placebo met the composite primary efficacy endpoint (p < 0.0001). Additionally, 93% (57/61) of participants treated with palopegteriparatide achieved independence from conventional therapy. Palopegteriparatide treatment normalised mean 24-hour urine calcium. Overall, 82% (50/61) treated with palopegteriparatide and 100% (21/21) with placebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred.

About YORVIPATH^® (palopegteriparatide)

YORVIPATH^® (palopegteriparatide, developed as TransCon™ PTH) is a once-daily prodrug providing sustained release of active PTH. It was approved by the European Union as a parathyroid hormone (PTH) replacement therapy for the treatment of adults with chronic hypoparathyroidism¹⁵ and the United States for the treatment of hypoparathyroidism in adults^13. Treatment should be initiated and monitored by physicians or qualified healthcare professionals experienced in the diagnosis and management of patients with hypoparathyroidism.

Yorvipath^® is a registered trademark of Ascendis Pharma A/S (NASDAQ: ASND).

References:

1. Therapeutic Goods Administration. Australian Register of Therapeutic Goods (ARTG). Available at: https://www.tga.gov.au/australian-register-therapeutic-goods. [Accessed Dec 2024].
2. YORVIPATH (palopegteriparatide) AU Product Information.
3. Therapeutic Goods Administration. Prescription medicine determinations and designations: Notice for palopegteriparatide (Specialised Therapeutics Pharma Pty Ltd) – Orphan drug designation. Available at: https://www.tga.gov.au/resources/designations-determinations/notice-palopegteriparatide-specialised-therapeutics-pharma-pty-ltd. [Accessed Dec 2024].
4. Therapeutic Goods Administration. Prescription medicine determinations and designations: Notice for palopegteriparatide (Specialised Therapeutics Pharma Pty Ltd) – Priority review. Available at: https://www.tga.gov.au/resources/designations-determinations/notice-palopegteriparatide-specialised-therapeutics-pharma-pty-ltd-0. [Accessed Dec 2024].
5. Siggelkow H, Pacaud D, et al. Clin Endocrinol (Oxf). 2020;92(2).
6. Bjornsdottir S, Sikjaer T, et al. J Bone Miner Res. 2022;37(12).
7. Australian Thyroid Foundation. Thyroid Facts: Parathyroid Glands – Hypoparathyroidism. Available at: https://thyroidfoundation.org.au/Parathyroid-Glands [Accessed Dec 2024].
8. National Organization for Rare Disorders. Disease Overview: Hypoparathyroidism - Symptoms, Causes, Treatment, 14 August 2024. Available at: https://rarediseases.org/rare-diseases/hypoparathyroidism/ [Accessed Dec 2024].
9. Endocrine Society. Endocrine Library: Patient Resources; Hypoparathyroidism, 24 January 2022. Available at: https://www.endocrine.org/patient-engagement/endocrine-library/hypoparathyroidism [Accessed Dec 2024].
10. Bilezikian JP. J Clin Endocrinol Metab. 2020;105(6):1722-1736. doi:10.1210/clinem/dgaa113.
11. YORVIPATH (palopegteriparatide) US Prescribing Information.
12. Khan AA, Bilezikian JP, Cusano NE, et al. J Bone Miner Res. 2023;38(1). 
13. US Food and Drug Administration. FDA approves new drug for hypoparathyroidism, a rare disorder, 9 August 2024. Available at: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-drug-hypoparathyroidism-rare-disorder [Accessed Dec 2024].
14. European Medicines Agency. Yorvipath: Palopegteriparatide, 17 November 2023. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/yorvipath [Accessed Dec 2024].
15. YORVIPATH (palopegteriparatide).EU Summary of Product Characteristics.