The decision by the TLV follows the Europe Commission approval in 2015 for asfotase alfa as a long-term ERT in patients with paediatric-onset HPP to treat the bone manifestations of the disease.²

HPP is a rare, lifelong and progressive metabolic disease caused by deficient activity of the enzyme alkaline phosphatase (ALP), which is important for building healthy bones as well as proper function of muscles.³ HPP is characterised by defective mineralisation (the process that hardens and strengthens bones and teeth), impaired calcium and phosphate regulation and non-skeletal manifestations, such as muscle weakness, neurologic symptoms, generalised fatigue and pain that can be debilitating.^3-5

Ola Nilsson MD, PhD, Professor of Paediatric Endocrinology Center for Molecular Medicine (CMM), Karolinska University Hospital, said: " Hypophosphatasia is a severe and debilitating metabolic bone disorder that can cause significant pain and suffering for affected individuals. The conclusion of TLV's evaluation, resulting in reimbursement, is highly positive. The fact that Swedish patients will now be able to receive an effective therapy is extremely encouraging and may help prevent disability, reduce suffering, and avert  premature death in individuals living with this condition.

Katri Köninki, Nordics Medical Lead, Alexion, said: "We're proud to mark a key milestone for the HPP community in Sweden, which now has an effective treatment option to address the substantial disease burden of this disease. We remain committed to advancing innovative therapies and working with clinicians, patient groups and institutions to deliver solutions where unmet need remains and improve the lives of people living with rare diseases."

About Hypophosphatasia (HPP)
Hypophosphatasia (HPP) is a rare, lifelong and progressive metabolic disease caused by deficient activity of the enzyme alkaline phosphatase (ALP), which is important for building healthy bones and supporting proper muscle function.³ HPP is characterised by defective mineralisation (the process that hardens and strengthens bones and teeth), impaired calcium and phosphate regulation and non-skeletal manifestations, such as muscle weakness, neurologic symptoms, generalised fatigue and pain that can be debilitating.^3-5 The signs and severity of HPP can be wide-ranging, worsen over time and affect people of all ages, .^3-6

Clinical Data
The approval of asfotase alfa in the United States and Europe was based on data from four pivotal clinical trials and supporting extension studies that included patients with HPP whose first manifestations occurred in childhood, treated with asfotase alfa for a maximum period of 7 years.

In patients (aged between 1 day and 5 years), treatment with asfotase alfa resulted in a significant survival benefit compared to patients in a historical control group with similar clinical characteristics. The results of the study also demonstrated substantial improvements in skeletal manifestations of HPP, as assessed by the Radiographic Global Impression of Change (RGI-C) scale, and improvements in height and weight, as measured by z-scores, in patients treated with asfotase alfa.^7-10

In patients (aged 6 to 12 years), treatment with asfotase alfa resulted in significant improvements in the skeletal manifestations of HPP at 24 weeks, as measured by the RGI-C, compared to historical controls. Importantly, at month 54, 100% of asfotase alfa-treated patients were treatment responders (n=8), as measured by substantial bone healing, compared to 6% of historical control patients (n=32) at last assessment. In addition, patients treated with asfotase alfa showed improvements in height and weight, measured by z-scores, compared to untreated historical controls, as well as improvements in gait and mobility.^7-10

The most commonly reported adverse events in clinical trials were reactions at the injection site. Other common adverse reactions were lipodystrophy, ectopic calcifications and hypersensitivity reactions.^7-10

Strensiq
Strensiq (asfotase alfa) is a bone-targeted enzyme replacement therapy designed to address the underlying cause of hypophosphatasia (HPP) - deficient alkaline phosphatase (ALP). By replacing deficient ALP, treatment with Strensiq aims to improve the elevated enzyme substrate levels and improve the body's ability to mineralise bone, thereby preventing serious skeletal and systemic patient morbidity and premature death.

Strensiq is approved in the US, EU, Japan and other countries for the treatment of certain patients with HPP.

Strensiq has been granted orphan drug designation by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Japanese Ministry of Health, Labour and Welfare (MHLW).

Alexion
Alexion, AstraZeneca Rare Disease, is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US.

AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

For press information:
Alexion, AstraZeneca Rare Disease
Ziba Zareie |ziba.zareie@alexion.comm| M +46 70 315 3544

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References

1. Dental and Pharmaceutical Benefits Agency of Sweden (TLV)
2. Strensiq (asfotase alfa) SmPC; September 2015
3. Rockman-Greenberg C. Hypophosphatasia. Pediatric Endocrinology Reviews. 2013;10(2):380-388.
4. Seefried L et al. Burden of illness in adults with hypophosphatasia: data from the Global Hypophosphatasia Patient Registry. J Bone Miner Res. 2020;35(11):2171-2178.
5. Dahir KM, et al. Clinical profiles of adults with and without hypophosphatasia in the Global HPP Registry. Orphanet J Rare Dis. 2022;17(1):277.
6. Fang S, et al. Diagnosed prevalence of hypophosphatasia in the United States: a real-world analysis of electronic health records [poster]. Poster presented at: Annual International Conference on Pharmacoepidemiology and Therapeutic Risk Management; 23-27 August 2023, Halifax, Nova Scotia, Canada.
7. Kishnani P, et al. Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. Bone. 2019;121:149-162.
8. Whyte MP, et al. Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial. The Lancet Diabetes & Endocrinology. 2019;7(2):93-105.
9. Hofmann CE, et al. Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2735-2747.
10. Whyte MP, et al. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016 Jun 16;1(9):e85971.