Strensiq ® - Asfotase alfa Manufacturer: Alexion FDA Approval Date: October 23, 2015

Strensiq ® - asfotase alfa Objectives At the end of this presentation participants will be able to: 1. Appropriately recommend Strensiq ® - (asfotase alfa) 2. Effectively educate patients on the purpose, proper use and potential adverse effects of Strensiq ® - (asfotase alfa)

Strensiq ® - asfotase alfa Clinical Application Indications: Treatment of perinatal-, infantile-, and juvenile-onset hypophosphatasia (HPP) Place in therapy: First and only treatment for perinatal-, infantile-, and juvenile-onset hypophosphatasia Strensiq ® [package insert].

Strensiq ® - asfotase alfa Clinical Application Contraindications: None Black Box warnings None Warnings & Precautions: Hypersensitivity reactions Lipodystrophy Ectopic calcifications (eye & kidney) Strensiq ® [package insert].

Strensiq ® - asfotase alfa Clinical Application Pregnancy: No human data Animal studies show no evidence of fetotoxicity, embryolethality, or teratogenicity Lactation: Unknown if excreted into breast milk Strensiq ® [package insert].

Strensiq ® - asfotase alfa Drug Facts Pharmacology: Replaces tissue nonspecific alkaline phosphatase (TNSALP) Strensiq ® [package insert].

Strensiq ® - asfotase alfa Drug Facts Pharmacokinetics: A Time to peak: 15 hours D Unknown M E T 1/2 ~5 days Strensiq ® [package insert].

Strensiq ® - asfotase alfa Drug Interactions Drug Interactions None known Strensiq ® [package insert].

Strensiq ® - asfotase alfa Adverse Effects Common Adverse Effects: (perinatal/infantile-onset HPP) [juvenile- onset HPP] Injection site reactions (56%) [90%] Ectopic calcifications (4%) [55%] Lipodystrophy (18%) [70%] Hypersensitivity reactions (13%) [10%] Strensiq ® [package insert].

Strensiq ® - asfotase alfa Monitoring Parameters Efficacy Monitoring: Improvement in respiratory status Growth Radiographic findings Toxicity Monitoring: Eye exam at baseline and periodically Kidney exam at baseline and periodically Strensiq ® [package insert].

Strensiq ® - asfotase alfa Prescription Information Dosing: 2 mg/kg 3 times a week or 1 mg/kg 6 times a week. May increase to 3 mg/kg 3 times a week if inadequate response for perinatal/infantile-onset HPP Cost: estimated $285,000 annually Strensiq ® [package insert]. OptumRx.com 04/04/2016

Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia Strensiq ® - asfotase alfa

Strensiq ® - asfotase alfa Literature Review Purpose: To study the safety and efficacy of asfotase alfa in perinatal/infantile-onset hypophosphatasia (HPP) Design: multinational, open-label Primary outcome: Healing of rickets Whyte MP, et al. N Engl J Med. 2012;366:

Strensiq ® - asfotase alfa Literature Review Inclusion criteria: <3 years old Symptoms of HPP occurring before 6 months of age HPP-related skeletal disease Failure to thrive Respiratory compromise from HPP Exclusion criteria Whyte MP, et al. N Engl J Med. 2012;366: Major coexisting disease Treatable form of rickets Hypocalcemia or hypophosphatemia Vit D<20 ng/ml

Strensiq ® - asfotase alfa Literature Review Intervention: 11 patients received asfotase alfa at a dose of 1 mg/kg 3 times per week. Dose could be increased to 3 mg/kg if there were: Worsening failure to thrive Deteriorating pulmonary function OR No radiographic evidence of skeletal improvement Whyte MP, et al. N Engl J Med. 2012;366:904-13

Strensiq ® - asfotase alfa Literature Review Primary outcome: change in skeletal manifestations of HPP i.e rickets Secondary outcome: improvement in respiratory status Whyte MP, et al. N Engl J Med. 2012;366:904-13

Strensiq ® - asfotase alfa Literature Review Results: Radiographic global impressions of change (RGI-C) score was assessed at baseline, week 24, and week 48 Week 24: 2.0 point increase Week 48: 2.3 point increase (p=0.004) Whyte MP, et al. N Engl J Med. 2012;366:904-13

Strensiq ® - asfotase alfa Literature Review Whyte MP, et al. N Engl J Med. 2012;366: Patient # Respiratory status at baseline Respiratory status at week 48 1CPAPAmbient air 2Progressive respiratory deteriorationTracheostomy & ventilation (only at night) 3Tracheostomy & ventilation 4 Dropped out 5Nasal cannula with O2Ambient air 6Progressive respiratory deteriorationAmbient air 7 8Progressive respiratory deteriorationAmbient air 9Progressive respiratory deteriorationNasal cannula with O2 10Progressive respiratory deteriorationAmbient air

Strensiq ® - asfotase alfa Literature Review Most common adverse event was injection site reactions Serious adverse events: Infections (50%) Respiratory disorders (30%) Nervous system disorders (20%) Musculoskeletal disorders (40%) Whyte MP, et al. N Engl J Med. 2012;366:904-13

Strensiq ® - asfotase alfa Literature Review Conclusion: Strensiq ® improved skeletal abnormalities and respiratory status in patients with perinatal/infantile-onset HPP Injection site reactions were the most common adverse event although there was no ectopic calcification in this study Whyte MP, et al. N Engl J Med. 2012;366:904-13

Strensiq ® - asfotase alfa Summary Strensiq ®, asfotase alfa, is a new novel agent and currently the only treatment available for perinatal-, infant-, and juvenile-onset hypophosphasia Subcutaneous dosing is weight based and either 2 mg/kg 3x per week or 1 mg/kg 6x per week Common adverse events are: injection site reaction, ectopic calcifications, and lipodystrophy Estimated annual cost is 285,000 Eye exams and renal ultrasounds should be monitored throughout therapy to monitor for ectopic calcifications

Strensiq ® - asfotase alfa References Strensiq ® package insert. Cheshire, CT: Alexion; Whyte MP, et al. Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia. N Engl J Med. 2012;366: