FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Vykat XR™ (diazoxide choline) Tablet |
Treatment of hyperphagia in adults and pediatric patients 4 years of age and older with Prader-Willi syndrome (PWS) |
|
1 |
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
|
Initial Evaluation Target Agent(s) will be approved when ALL of the following are met: 1. ONE of the following: A. The patient has a diagnosis of Prader-Willi syndrome and BOTH of the following: 1. The patient has hyperphagia AND 2. The patient's diagnosis has been confirmed by genetic testing indicating mutation on chromosome 15 (medical records required) OR B. The patient has another FDA labeled indication for the requested agent and route of administration AND 2. If the patient has an FDA labeled indication, then ONE of the following: A. The patient’s age is within FDA labeling for the requested indication for the requested agent OR B. There is support for using the requested agent for the patient’s age for the requested indication AND 3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist, geneticist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 4. The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.
Renewal Evaluation 1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND 2. The patient has had clinical benefit with the requested agent AND 3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist, geneticist), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 4. The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
PRIOR AUTHORIZATION CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
Module |
Ops Set Up |
Validation Options |
Other Explanation |
|
Documentation: Requirements as noted within the policy;Validation: Apply Baseline and go to Validation Options |
Age Verification;Continuation of Therapy;Diagnosis |
|
QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
Universal QL |
Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met: 1. The requested quantity (dose) does NOT exceed the program quantity limit OR 2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following: A. BOTH of the following: 1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND 2. There is support for therapy with a higher dose for the requested indication OR B. BOTH of the following: 1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND 2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR C. BOTH of the following: 1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND 2. There is support for therapy with a higher dose for the requested indication Length of Approval: up to 12 months |
QUANTITY LIMIT CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
Module |
Ops Set Up |
Validation Options |
Other Explanation |
Universal QL |
Validation: Apply Baseline and go to Validation Options |
|
|
Prader-Willi Syndrome |
Prader-Willi syndrome (PWS) is a genetic multisystem neurodevelopmental disorder characterized during infancy by lethargy and severe hypotonia (diminished muscle tone, leading to difficulty in sucking and feeding during infancy), before progressing to overeating and the gradual development of morbid obesity from childhood to adulthood. Without intervention, overeating can lead to onset of life-threatening obesity. Individuals with severe obesity may have an increased risk of cardiac insufficiency, sleep apnea, diabetes, respiratory problems and other serious conditions that can cause life-threatening complications. All individuals with PWS have some cognitive impairment that ranges from low normal intelligence with learning disabilities to mild to moderate intellectual disability. Behavioral problems are common and can include temper tantrums, obsessive/compulsive behavior and skin picking. Motor milestones and language development are often delayed.(2,3,5) PWS results from the absence of gene expression of the paternally inherited genes on the 15q11.2-q13 chromosome. Approximately 70% of cases result from errors in genomic imprinting due to a paternal deletion, while maternal uniparental disomy is responsible for about 25% of cases. Fewer cases stem from defects in the imprinting center, such as microdeletions or epimutations on chromosome 15.(2,4,5) Consensus diagnostic criteria for PWS have been established and are effective for identifying potential cases of PWS, but genetic testing is required to confirm the diagnosis and to identify the specific genetic subtype (paternally-inherited 15q11-q13 deletion, uniparental disomy of the maternal chromosome 15, imprinting center defects). Hence, all infants and newborns with unexplained hypotonia and poor suck should be tested for PWS. To confirm a diagnosis of PWS, certain specialized tests are required including DNA methylation tests and fluorescent in situ hybridization (FISH).(2,4,5) More recently, high resolution chromosomal microarray studies with several hundred thousand DNA probes from throughout the genome representing all chromosomes can be utilized to identify small deletions or duplications of the chromosomes that cannot be seen with routine chromosome studies. High resolution chromosome microarrays are most useful in identifying the typical chromosome 15q11-q13 deletions in which there are two types (larger type I and smaller type II), other rearrangements of this chromosome region, imprinting defects and specific maternal disomy 15 subclasses seen in PWS. Genetic laboratory testing algorithms and advances in genetic technology have allowed more precise testing results and PWS molecular genetic class identified which is important as the severity of clinical findings, disease surveillance and recurrence risks can depend on the specific genetic abnormality.(5) Hyperphagia in PWS is believed to be caused by a hypothalamic abnormality resulting in lack of satiety. Food-seeking behaviors such as hoarding or foraging for food, eating of inedible objects, and stealing of food or money to buy food are common. At this time there are no consistently identified hormonal abnormalities to explain the hyperphagia, and the metabolic correlates of hyperphagia in PWS remain uncertain.(2,3,4) The possible mechanism(s) may include increased ghrelin and leptin, as well as low levels of thyroid hormone, low peptide YY (PYY), and insulin. The function of PYY and insulin are to stimulate pro-opiomelanocortin (POMC) neurons and inhibit neuropeptide Y (NPY; an appetite-stimulating peptide), followed by activation of melanocortin receptor 4 (MC4R) to induce satiety. PWS individuals have low levels of PYY and insulin, so NPY is released which prevents MC4R activation (leading to increased food intake). Potential treatments to correct PYY and insulin abnormalities are topiramate (reduces NPY levels), setmelanotide (activates MC4R to induce satiety), and diazoxide (reduces NPY secretion).(3) |
Efficacy |
The efficacy of Vykat XR for the treatment of hyperphagia in adults and pediatric patients ages 4 years and older with PWS was established in a 16-week, double-blind, placebo-controlled, randomized withdrawal study period (Study 2-RWP; NCT03714373) that followed an open-label study period of Vykat XR. During Study 2-RWP, 77 patients with hyperphagia and PWS were randomized in a 1:1 ratio to continue their current oral dosage using a weight-based dosage regimen of Vykat XR (n=38) or placebo (n=39). Prior to participating in Study 2-RWP, patients received double-blind and/or open-label Vykat XR for a mean duration of 3.3 years (range 2.5 to 4.5 years; Study 1 and Study 2-OLE).(1) The primary endpoint was the change from baseline to week 16 in hyperphagia using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT) total score, an instrument designed to measure symptoms of food-related preoccupations and behaviors. Scores can range from 0 to 36, with higher scores indicating greater overall severity of hyperphagic and food-related behaviors. Findings showed a statistically significant worsening of hyperphagia in patients who received placebo compared with those who received diazoxide choline extended-release (HQ-CT total score, least square mean difference: -5.0 [-8.1, -1.8]).(1) |
Safety |
Vykat XR is contraindicated in patients with known hypersensitivity to diazoxide, other components of Vykat XR, or thiazides. Erythema multiforme has been reported with Vykat XR.(1) |
Number |
Reference |
1 |
Vykat XR prescribing information. Soleno Therapeutics, Inc. March 2025. |
2 |
Driscoll DJ, Miller JL, Cassidy SB. Prader-Willi syndrome. 1998 Oct [Last updated 2024 Dec]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1330/ |
3 |
Ab Rahman QF, Jufri NF, Hamid A. Hyperphagia in Prader-Willi syndrome with obesity: From development to pharmacological treatment. Intractable Rare Dis Res. 2023 Feb;12(1):5-12. doi: 10.5582/irdr.2022.01127 |
4 |
Prader-Willi Syndrome Association. Prader-Willi syndrome medical alerts. Last updated 2022. Available at: https://www.pwsausa.org/wp-content/uploads/2022/04/MedicalAlertsBooklet-GIChart-2022.pdf |
5 |
National Organization for Rare Disorders (NORD). Prader-Willi syndrome. Last updated July 2023. Available at: https://rarediseases.org/rare-diseases/prader-willi-syndrome/ |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Final Module |
Target Agent GPI |
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Targeted NDCs When Exclusions Exist |
Final Age Limit |
Preferred Status |
Effective Date |
|
|||||||||
|
309028302075 |
Vykat xr |
diazoxide choline tab er |
150 MG ; 25 MG ; 75 MG |
M ; N ; O ; Y |
|
|
|
|
POLICY AGENT SUMMARY QUANTITY LIMIT
Target Agent GPI |
Target Brand Name(s) |
Target Generic Name(s) |
Strength |
QL Amount |
Dose Form |
Days Supply |
Duration |
Targeted NDCs When Exclusions Exist |
Age Limit |
Effective Date |
Term Date |
|
|||||||||||
30902830207510 |
Vykat xr |
diazoxide choline tab er |
25 MG |
120 |
Tablets |
30 |
DAYS |
|
|
|
|
30902830207520 |
Vykat xr |
diazoxide choline tab er |
75 MG |
210 |
Tablets |
30 |
DAYS |
|
|
|
|
30902830207530 |
Vykat xr |
diazoxide choline tab er |
150 MG |
90 |
Tablets |
30 |
DAYS |
|
|
|
|
CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Client Formulary |
|
|||
Vykat xr |
diazoxide choline tab er |
150 MG ; 25 MG ; 75 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
|
|||
Vykat xr |
diazoxide choline tab er |
25 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
Vykat xr |
diazoxide choline tab er |
75 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
Vykat xr |
diazoxide choline tab er |
150 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
