Pharmacy Prior Authorization Criteria

Strensiq (asfotase alfa)

Indications for Prior Authorization

Strensiq (asfotase alfa)

• For diagnosis of Perinatal/infantile- and juvenile-onset hypophosphatasia (HPP)
  Indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).

Criteria

Strensiq*

*If criteria above are met and the 80mg strength is requested, see table in the Background Section for auth approval instructions. For all other strengths, approve auth at GPI-14 level if criteria above are met. **Consultation with a specialist should not be accepted. Must be prescribed by a specialist experienced in the treatment of inborn errors of metabolism.

Prior Authorization (Initial Authorization)

Length of Approval: 6 Month(s)

• Submission of medical records (e.g., chart notes) documenting all of the following:
• One of the following diagnoses:
• Perinatal/infantile-onset hypophosphatasia (HPP)
• Juvenile-onset hypophosphatasia (HPP)
AND
• Onset of clinical signs and symptoms of hypophosphatasia prior to age 18 years (e.g., respiratory insufficiency, vitamin B6 responsive seizures, hypotonia, failure to thrive, delayed walking, waddling gait, dental abnormalities, low trauma fractures) [A-D; 1, 7-9]
AND
• Radiographic evidence supporting the diagnosis of hypophosphatasia at the age of onset prior to age 18 (e.g., infantile rickets, craniosynostosis, non-traumatic fractures, osteoporosis or low bone mineral content for age [as detected by DEXA]) [A-D; 1, 7-9]
AND
• One of the following: [F-G; 2-6, 8]
• Both of the following:
• Patient has low level activity of serum alkaline phosphatase (ALP) evidenced by an ALP level below the age and gender-adjusted normal range
AND
• Patient has an elevated level of tissue non-specific alkaline phosphatase (TNSALP) substrate (e.g., serum pyridoxal 5’-phosphate [PLP] level, serum or urine phosphoethanolamine [PEA] level, urinary inorganic pyrophosphate [PPi level])
OR
• Confirmation of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutation by ALPL genomic DNA testing
AND
• Prescribed by a specialist experienced in the treatment of inborn errors of metabolism (e.g., endocrinologist, rheumatologist, geneticist, orthopedist) [H; 2-6]**
AND
• Requested dose will not exceed the following: [H,1] (Note to prescriber: Three times a week dosing leads to less waste and may lead to less injection site reactions compared to six times a week dosing)
• 9 mg/kg per week for perinatal/infantile-onset HPP
• 6 mg/kg per week for juvenile-onset HPP
AND
• If patient weighs less than 40 kg, the 80 mg/0.8mL vial will not be approved (patient’s weight must be provided)

Strensiq*

*If criteria above are met and the 80mg strength is requested, see table in the Background Section for auth approval instructions. For all other strengths, approve auth at GPI-14 level if criteria above are met. **Consultation with a specialist should not be accepted. Must be prescribed by a specialist experienced in the treatment of inborn errors of metabolism.

Prior Authorization (Reauthorization)

Length of Approval: 9 Month(s)

• The patient has responded to treatment with Strensiq as evidenced by one of the following: [1, 7-9]
• Improvement and/or stabilization of clinical signs and/or symptoms of hypophosphatasia (e.g., respiratory status [ventilator free survival], growth) or radiographic findings (e.g., skeletal manifestations)
• Clinically relevant decrease from baseline in tissue non-specific alkaline phosphatase (TNSALP) substrate (e.g., serum pyridoxal 5’-phosphate [PLP] level, serum or urine phosphoethanolamine [PEA] level, urinary inorganic pyrophosphate [PPi level])
AND
• Prescribed by a specialist experienced in the treatment of inborn errors of metabolism (e.g., endocrinologist, rheumatologist, geneticist, orthopedist) [H, 2-6]**
AND
• Requested dose will not exceed the following: [H, 1] (Note to prescriber: Three times a week dosing leads to less waste and may lead to less injection site reactions compared to six times a week dosing)
• 9 mg/kg per week for perinatal/infantile-onset HPP
• 6 mg/kg per week for juvenile-onset HPP
AND
• If patient weighs less than 40 kg, the 80 mg/0.8mL vial will not be approved (patient’s weight must be provided)

Strensiq

*Note: Requests will be denied as medical necessity.

Quantity Limit*

• For the 80mg/0.8mL vial, requests for additional quantity will not be approved

P & T Revisions

2024-06-04, 2024-04-03, 2023-06-27, 2023-03-28, 2023-03-21, 2022-10-17, 2022-06-20, 2021-11-02, 2021-07-06, 2021-05-26, 2021-05-25, 2020-06-16

References

1. Strensiq prescribing information, Alexion Pharmaceuticals. Cheshire, CT. June 2020.
2. Hickman-Simmons, Jill. Best Practices in: Recognizing and Diagnosing Hypophosphatasia. Clinical Endocrinology News. November 2013. Available at: www.clinicalendocrinologynews.com/resources/best-practices.html. Accessed June 15, 2020.
3. Hofmann C, Rockman-greenberg C, Harmatz P, Moseley S, Odrljin T, Liese J. Improvement in bone manifestations and respiratory status in infants and young children with HPP treated with asfotase alfa: An update on the ENB-010-10 trial. In: Oral Presentation Presented at the 7th International Conference on Children’s Bone Health. 27-30 June 2015. Salzburg, Austria.
4. Madson KL, Rockman-Greenberg C, Melian A, et al. Asfotase alfa: long-term safety and efficacy in children with hypophosphatasia. Poster presented at the Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting; May 3-6, 2014; Vancouver, Canada.
5. Rockman-Greenberg C, Vockley J, Harmatz P, et al. Asfotase alfa improves skeletal mineralization and respiratory function in infants and young children with hypophosphatasia: results from up to 12 months’ treatment. Poster presented at the 2014 ACMG Annual Meeting; March 25-29, 2014; Nashville, TN.
6. Whyte MP, Greenberg CR, Salman N, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012; 366(10):904-913.
7. Epps, C. Center for Drug Evaluation and Research Application Number: 125513ORIG1S000 Medical Review(s). 2015 October. Available at HTTPS://WWW.ACCESSDATA.FDA.GOV/DRUGSATFDA_DOCS/NDA/2015/125513ORIG1S000MEDR.PDF. Accessed October 4, 2021.
8. Whyte, M. Hypophosphatasia. NORD- National Organization for Rare Disorders.Available at https://rarediseases.org/rare-diseases/hypophosphatasia/. Accessed october 4, 2021.
9. Orimo, H. Pathophysiology of hypophosphatasia and the potential role of asfotase alfa. Ther Clin Risk Manag. 2016; 12: 777–786. Available at doi: 10.2147/TCRM.S87956. Accessed October 22, 2021
10. Reis, F., Lazaretti-Castro, M. Hypophosphatasia: from birth to adulthood. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665056/. Accessed June 4, 2024.

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End Notes

1. Study 1 was a 24-week prospective single-arm trial in 11 patients, 7/11(64%) were female and 10/11(91%) were white, aged 3 weeks to 39.5 months with severe perinatal/infantile-onset HPP. Severe perinatal/infantile onset HPP was defined as biochemical, medical history and radiographic evidence of HPP as well as the presence of any of the following: rachitic chest deformity, vitamin B6 dependent seizures, or failure to thrive.[1]
2. HPP is diagnosed by identifying its symptoms and complications beginning with a detailed patient history. HPP signs are revealed by a thorough clinical examination, and supported by routine x-rays and various laboratory tests including biochemical studies. [8]
3. The clinical review team concluded that the totality of evidence, including growth, radiographic, and histomorphometric data collected in both populations and survival data collected in the perinatal/infantile-onset population, were sufficient to make a favorable medical risk benefit determination for approval for the juvenile-onset indication. [7]
4. Clinical course Perinatal-onset HPP typically is diagnosed on prenatal ultrasound examination which demonstrates unmineralized or hypomineralized bone. As noted earlier, the lethal perinatal form results in stillbirth or early neonatal death secondary to pulmonary insufficiency caused by chest wall deformities (flail chest). Other clinical features may include fever, anemia, failure to thrive, irritability, apnea and bradycardia, intracranial hemorrhage and pyridoxine-dependent seizures. The benign perinatal form clinically resembles other milder forms of HPP. Infantile-onset HPP presents before age six months of age, with infants developing clinical signs and symptoms of rickets, including growth failure, hypotonia, bowing of long bones, and rachitic changes of the ribs. Other clinical hallmarks are wide fontanels (actually hypomineralized skull bone) and craniosynostosis. Other skull deformities may include hypertelorism and brachycephaly. Infantile-onset HPP patients are at increased risk of pneumonia due to flail chest In juvenile-onset HPP (also termed as childhood HPP), premature loss of the primary teeth (prior to age 5 years) is a major clinical hallmark of disease. Radiographic evidence of dental hypoplasia may precede radiographic evidence of skeletal disease. Patients who develop rickets may have delayed walking, gait abnormalities (waddling gait) and short stature. Other complications include pathologic fractures, most commonly involving the metaphysis, and static myopathy. Patient may also experience bone pain and stiffness. Some patients may improve spontaneously during puberty, with recurrence of skeletal symptoms during adulthood. As in infantile-onset HPP, patients with juvenile-onset HPP may develop nephrocalcinosis. Dental involvement of secondary dentition is generally less severe Adult-onset HPP usually presents during middle age, with about 50% of patients having a history of rickets and or premature dental loss during childhood. The chief clinical features of adult-onset HPP are recurrent stress fractures and femoral pseudofractures (areas of osteomalacia). Patients also may experience hip or thigh pain (secondary to femoral pseudofractures) and may develop chondrocalcinosis [7, 9]
5. HPP is a rare metabolic disease characterized by low serum alkaline-phosphatase activity which results in bone mineralization defects and various systemic complications [2, 6] The disease arises from a genetic mutation within the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). The mutation results in a loss of function which leads to an accumulation of TNSALP substrates (e.g., inorganic pyrophosphate and pyridoxal 5′-phosphate (PLP). Given the complexities and rarity of the condition, the criteria requires the medication to be prescribed by or in consultation with a specialist experienced in the treatment of inborn errors of metabolism, this aims to ensure proper diagnosis.
6. HPP is caused by mutations in the ALPL gene. This is the only gene that causes HPP. The ALPL gene creates (encodes) a type of protein called an enzyme named TNSALP. Enzymes are specialized proteins that break down specific chemicals in the body. TNSALP is essential for the proper development and health of bones and teeth, and is abundant in the skeleton, liver, and kidneys. Mutations in the ALPL gene lower the activity of TNSALP, in turn leading to accumulation of phosphoethanolamine (PEA), pyridoxal 5’-phosphate (PLP), and inorganic pyrophosphate (PPi). [8]
7. HPP is a rare metabolic disease characterized by low serum alkaline-phosphatase activity which results in bone mineralization defects and various systemic complications [2, 6] The disease arises from a genetic mutation within the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). The mutation results in a loss of function which leads to an accumulation of TNSALP substrates (e.g., inorganic pyrophosphate and pyridoxal 5′-phosphate (PLP). Given the complexities and rarity of the condition, the criteria requires the medication to be prescribed by or in consultation with a specialist experienced in the treatment of inborn errors of metabolism, this aims to ensure proper diagnosis.
8. The 80 mg/0.8 mL vial should not be used in patients weighing less than 40 kg, as the systemic exposure of the drug is lower than that achieved within the lower strengths. Use in these patients could result in inadequate exposure and poor treatment outcomes. [1]

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Revision History

• 2024-06-04: 2024 Annual Review
• 2024-04-03: Added operational note. No changes to clinical criteria.
• 2023-06-27: 2023 Annual Review
• 2023-03-28: Update to operational note.
• 2023-03-21: No changes to criteria. Updated operational note and background section.
• 2022-10-17: Program update.
• 2022-06-20: 2022 Annual Review
• 2021-11-02: 2021 Annual Review
• 2021-07-06: Annual Review
• 2021-05-26: Addition of EHB formulary to guideline, no changes to criteria
• 2021-05-25: Addition of EHB formulary to guideline, no changes to criteria
• 2020-06-16: Annual Review - No Changes

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