Products

Date: 2015-10-23

Type of information: Granting of a Market Authorisation in the US

Product name: Strensiq®

Compound: asfotase alfa

Therapeutic area: Rare diseases - Bone diseases - Genetic diseases - Metabolic diseases

Action mechanism:

• enzyme replacement therapy (ERT). Asfotase alfa is an investigational, highly innovative, first-in-class targeted alkaline phosphatase enzyme replacement therapy. Asfotase alfa is designed to address the underlying cause of HPP by normalizing the genetically defective metabolic process, and preventing or reversing the severe and potentially life-threatening complications of life-long dysregulated mineral metabolism.
• In 2013, the FDA granted Breakthrough Therapy designation for asfotase alfa.
• Asfotase alfa (ENB-0040) has been developed by the Canadian company Enobia Pharma. On December 28, 2011, Alexion Pharmaceuticals and Enobia Pharma announced that the companies have signed a definitive agreement under which Alexion will acquire 100% of the capital stock of Enobia. Under the terms of the agreement, Alexion has agreed to pay $610 million in cash upon consummation of the transaction, and up to $470 million in cash to be paid upon achievement of various regulatory and sales milestones.

Company: Alexion Pharmaceuticals (USA - CT)

Disease: hypophosphatasia  

Latest news:

• • On July 5, 2017, Alexion Pharmaceuticals announced that it has reached a national funding agreement with the National Institute for Health and Care Excellence (NICE) and the National Health Service (NHS) England based on a Managed Access Agreement, which provides access to Strensiq® (asfotase alfa) for patients in England with pediatric-onset hypophosphatasia, regardless of their current age. The funding agreement was announced in a positive final evaluation determination (FED) issued by the NICE Highly Specialised Technologies (HST) Evaluation Committee to recommend Strensiq® according to the MAA.
• • On October 23, 2015, Alexion Pharmaceuticals announced that the FDA has approved Strensiq™ (asfotase alfa) for the treatment of patients with perinatal-, infantile- and juvenile-onset hypophosphatasia.
• Strensiq™ is the first therapy approved in the U.S. for the treatment of patients with hypophosphatasia. The FDA approved Strensiq™ under Priority Review. With this approval, the FDA also issued a Rare Pediatric Disease Priority Review Voucher, which confers priority review to a subsequent drug application that would not otherwise qualify for priority review.
• The approval of Strensiq™ in the U.S. was based on data from four clinical trials and supporting extension trials comprising patients with perinatal-, infantile- and juvenile-onset hypophosphatasia who received treatment with Strensiq™ for up to 6.5 years. In patients (ages 1 day to 6.5 years) with perinatal/infantile-onset HPP, treatment with Strensiq resulted in a significant survival benefit compared to historical control patients with similar clinical characteristics. At week 48, the Kaplan-Meier estimate of overall survival was 97 percent for treated patients (n=68) compared to 42 percent for historical control patients (n=48). In addition, estimated invasive ventilator-free survival was 96 percent for treated patients (n=54) compared to 31 percent for historical control patients (n=48). Study results also demonstrated substantial improvements in the skeletal manifestations of hypophosphatasia, 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 Strensiq.
• In patients (ages 6 to 12 years) with juvenile-onset hypophosphatasia, treatment with Strensiq™ resulted in significant improvements in the skeletal manifestations of hypophosphatasia at 24 weeks, as measured by RGI-C, compared to historical controls. Importantly, by month 54, 100 percent of Strensiq-treated juvenile-onset patients were responders to treatment (n=8), as measured by substantial bone healing, compared to 6 percent of patients in the historial control group (n=32) at last assessment. In addition, patients treated with Strensiq™ had improvements in height and weight, as measured by z-scores, compared with untreated historical controls, as well as improvements in gait and mobility. By 4 years of treatment, 100 percent of patients assessed (n=6) achieved the 6 Minute Walk Test within the normal range for age-, sex- and height-matched peers, whereas no patients were in the normal range at baseline.
• The most commonly reported adverse events observed in clinical trials were injection site reactions. Other common adverse reactions included lipodystrophy, ectopic calcifications, and hypersensitivity reactions.
• Alexion will offer support to patients with hypophosphatasia through its OneSource™ program. OneSource provides each patient and family with personalized support from a dedicated Alexion nurse case manager, who can help patients understand their insurance benefits, receive reimbursement assistance, and provide education support such as in-home injection training. Through OneSource, patients and families can obtain further information regarding third-party foundations and co-pay assistance programs, which help patients meet out-of-pocket expenses related to the treatment of hypophosphatasia. For uninsured patients who have no access to insurance, the Alexion Access Foundation, a charitable entity, provides Strensiq free of charge for patients. Alexion will now begin serving patients with hypophosphatasia in the U.S., with Strensiq becoming available commercially by October 27, 2015.
• • On September 1, 2015, Alexion Pharmaceuticals announced that the European Commission has approved Strensiq™ (asfotase alfa) for long-term enzyme replacement therapy in patients with pediatric-onset hypophosphatasia  to treat the bone manifestations of the disease. Strensiq® is the first therapy approved in the European Union (EU) for the treatment of patients with hypophosphatasia. Alexion expects to begin serving patients in Germany in October and is now commencing reimbursement processes with healthcare authorities in each of the major European countries.
• The approval of Strensiq® in the EU was based on clinical data from four pivotal prospective studies and their extensions, comprising 68 patients with pediatric-onset HPP (ranging from newborns to 66 years of age). Study results showed that patients with pediatric-onset HPP treated with Strensiq demonstrated rapid and sustained improvements in bone mineralization, as measured by the Radiographic Global Impression of Change (RGI-C) scale, which evaluates the severity of rickets based on X-ray images. Patients in the clinical studies also had improvements in skeletal structure, as demonstrated by x-ray appearance of joints, by histological appearance of bone biopsy material, and by apparent catch-up height-gain. The most common adverse reactions observed in clinical studies were injection site reactions and injection-associated adverse reactions. Most of these reactions were non-serious and mild to moderate in intensity.
• • On June 25, 2015, the Committee for Medicinal Products for Human Use (CHMP) has recommended granting a marketing authorisation under exceptional circumstances for Strensiq® (asfotase alfa), for the long-term treatment of hypophosphatasia. There is currently no approved treatment for this condition; patients usually receive supportive treatment such as plaster casts for broken bones, calcium supplements for maintaining the levels of calcium in the blood and painkillers. Strensiq, the first therapy for this disease, could contribute to respond to this unmet medical need as it is expected to help improve the composition of bones and make them stronger. The Committee for Medicinal Products for Human Use (CHMP) considered that Strensiq® should be recommended for marketing authorisation under exceptional circumstances. This type of authorisation can be granted for medicines that offer new or improved treatment options for patients with no or only limited alternatives, in cases where the applicant is not able to provide comprehensive data. In the case of Strensiq®, data on the efficacy and safety are limited due to the extreme rarity of the disease. However, CHMP required the applicant to collect further data on its clinical efficacy and safety and submit these data regularly for review by the Committee after the granting of a marketing authorisation.
• • On March 2, 2015, Alexion Pharmaceuticals announced that the FDA has accepted for Priority Review the Company’s Biologics License Application (BLA) for asfotase alfa for treatment of patients with infantile- and juvenile-onset hypophosphatasia. The BLA submission is supported by data from 71 treated patients with HPP enrolled in three prospective studies and their extensions, as well as two retrospective natural history studies. In May 2013, the FDA granted Breakthrough Therapy designation for asfotase alfa and in April 2014, Alexion initiated the rolling submission of the BLA.
• • On December 30, 2014, Alexion Pharmaceuticals announced completion of the rolling submission of a Biologics License Application (BLA) to the FDA for asfotase alfa for the treatment of hypophosphatasia. The BLA submission includes data from 71 treated patients with  hypophosphatasia enrolled in three prospective studies and their extensions, as well as a retrospective natural history study in infants with  hypophosphatasia and a separate retrospective natural history study in juveniles with hypophosphatasia.
• • On September 8, 2014, Alexion Pharmaceuticals announced that Japan’s Ministry of Health, Labour and Welfare (MHLW) has granted orphan drug designation (ODD) to asfotase alfa for the treatment of patients with hypophosphatasia.
• • On July 24, 2014, Alexion Pharmaceuticals announced that the Marketing Authorization Application (MAA) for asfotase alfa has been validated and granted accelerated assessment by the European Medicines Agency (EMA). The acceptance of this MAA marks the beginning of the review process in the European Union (EU) for this potential new treatment. The EU filing includes positive data from 68 patients with pediatric-onset  hypophosphatasia (ranging from newborns to 66 years of age) enrolled in three pivotal prospective studies and their extensions, as well as a retrospective natural history study in infants. In April, Alexion initiated the rolling submission of a Biologics License Application (BLA) for asfotase alfa as a treatment for patients with HPP with the FSA.

Patents:

Submission of marketing authorization application USA : 2014-12-30

Submission of marketing authorization application UE: 2014-07-24

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2015-10-23

UE authorization: 2015-09-01

Favourable opinion UE: 2015-06-25

Favourable opinion USA:

Orphan status USA: 2008-09-12

Orphan status UE: 2008-03-12

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

 

Is general: Yes