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ph-91138

Dojolvi Prior Authorization Program Summary

Policy Number: PH-91138

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
01-01-2025	01-01-2021

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Dojolvi® (triheptanoin) Oral liquid	A source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD)		1

Agent(s)

FDA Indication(s)

Notes

Ref#

Dojolvi®

(triheptanoin)

Oral liquid

A source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (LC-FAOD)

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Long Chain Fatty Acid Oxidation Disorders

Long-chain fatty acid oxidation disorders (LC-FAODs) are rare, life-threatening, autosomal recessive genetic disorders characterized by acute crises of energy production and chronic energy deficiency. Patients may present with rhabdomyolysis induced by exercise; fasting or illness; hepatic dysfunction, including severe hypoglycemia and hyperammonemia; and cardiomyopathy. These clinical manifestations can lead to frequent hospitalizations and premature death. LC-FAODs are caused by mutations in nuclear genes encoding mitochondrial enzymes involved in the conversion of dietary long-chain fatty acids (LCFAs) into energy during times of fasting and physiologic stress.(2)

Fatty acid oxidation disorders are often captured as part of newborn screenings. A plasma acylcarnitine profile is necessary for diagnosis following an abnormal NBS. DNA testing is considered standard for confirmation and can be helpful in genotype/phenotype correlations. DNA sequencing may reveal variants of uncertain significance, so further investigation of enzyme activity through fibroblast or lymphocyte testing may provide additional information of functional significance.(3,4,5)

Current management options leave many patients continuing to experience major clinical events, and mortality rates remain elevated. The current standard therapy for LC-FAODs is avoidance of fasting as well as supplementation of medium-chain triglyceride oil which does not require the typical steps of LC-FAOD for metabolism. Despite this therapy, patients with LC-FAODs continue to experience recurring hospitalizations, and high morbidity and mortality rates. In recent years, the use of medium, odd-chain fatty acids, such as triheptanoin, have been studied as a treatment of LC-FAODs due to its anaplerotic (replenishment of metabolic pathway intermediates) properties. Due to favorable safety and efficacy data from clinical trials, this novel agent has the potential to transform the treatment of LC-FAODs and improve patient outcomes in this patient population.(2,3)

Efficacy

The efficacy of triheptanoin as a source of calories and fatty acids was evaluated in Study 3 (NCT01379625), a 4-month double-blind randomized controlled study comparing triheptanoin (7-carbon chain fatty acid) with trioctanoin (8-carbon chain fatty acid). The study enrolled 32 adult and pediatric patients with a confirmed diagnosis of LC-FAOD and evidence of at least one significant episode of rhabdomyolysis and at least two of the following diagnostic criteria: disease specific elevation of acylcarnitines on a newborn blood spot or in plasma, low enzyme activity in cultured fibroblasts, or one or more known pathogenic mutations in CPT2, ACADVL, HADHA, or HADHB. The dosage of study drug was titrated to a protocol-specified target of 20% DCI (actual mean daily dose achieved was 16% for triheptanoin and 14% for trioctanoin). The recommended target dosage of Dojolvi is up to 35% of DCI. After 4 months, patients in both groups had similar mean changes from baseline in left ventricular ejection fraction and wall mass on resting echocardiogram and similar maximal heart rates on treadmill ergometry.(1)

Safety

Triheptanoin carries no contraindications nor boxed warnings.(1)

REFERENCES

Number	Reference
1	Dojolvi prescribing information. Ultragenyx Pharmaceutical Inc. October 2023.
2	Vockley J. Long-Chain Fatty Acid Oxidation Disorders and Current Management Strategies. Am J Manag Care. 2020 Aug;26(7 Suppl):S147-S154.
3	Baker JJ, Burton BK. Diagnosis and Clinical Management of Long-chain Fatty-acid Oxidation Disorders: A Review. TouchREV Endocrinol. 2021 Nov;17(2):108-111.
4	Knottnerus SJG, Bleeker JC, Wust RCI, et al. Disorders of Mitochondrial Long-Chain Fatty Acid Oxidation and the Carnitine Shuttle. Rev Endocr Metab Disord. 2018;19(1):93-106.
5	Merritt JL, Norris M, Kanungo S. Fatty Acid Oxidation Disorders. Ann Transl Med. 2018;6(24):473.

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)	Target Generic Agent(s)	Strength	Targeted MSC	Available MSC	Final Age Limit	Preferred Status

Dojolvi	triheptanoin oral liquid	100 %	M ; N ; O ; Y	N

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Dojolvi	triheptanoin oral liquid	100 %	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Initial Evaluation Target Agent will be approved when ALL of the following are met: The patient has ONE of the following: The patient has a diagnosis of long-chain fatty acid oxidation disorder (LCFAOD) AND ALL of the following: The diagnosis has been confirmed by at least TWO of the following: Disease-specific elevations of acylcarnitines on a newborn blood spot or in plasma Enzyme activity assay (in cultured fibroblasts or lymphocytes) demonstrating deficiency of an enzyme associated with LCFAODs Genetic testing demonstrating pathogenic mutation in a gene associated with LCFAODs AND The patient had symptomatic LCFAOD prior to therapy with the requested agent AND The patient will not be concurrently using another medium chain triglyceride product AND The patient will not be using the requested agent for more than 35% of the patient’s total prescribed daily caloric intake OR The patient has another FDA labeled indication for the requested agent and route of administration OR The patient has another indication that is supported in compendia for the requested agent and route of administration AND The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence Renewal Evaluation Target Agent will be approved when ALL of the following are met: 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 The patient has had clinical benefit with the requested agent AND If the patient has a diagnosis of LCFAOD, BOTH of the following: The patient will not be concurrently using another medium chain triglyceride product AND The patient will not be using the requested agent for more than 35% of the patient's total prescribed daily caloric intake AND The prescriber is a specialist in the area of the patient’s diagnosis (e.g. endocrinologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months

Module

Clinical Criteria for Approval

Initial Evaluation

Target Agent will be approved when ALL of the following are met:

The patient has ONE of the following:
1. The patient has a diagnosis of long-chain fatty acid oxidation disorder (LCFAOD) AND ALL of the following:
  1. The diagnosis has been confirmed by at least TWO of the following:
    1. Disease-specific elevations of acylcarnitines on a newborn blood spot or in plasma
    2. Enzyme activity assay (in cultured fibroblasts or lymphocytes) demonstrating deficiency of an enzyme associated with LCFAODs
    3. Genetic testing demonstrating pathogenic mutation in a gene associated with LCFAODs AND
  2. The patient had symptomatic LCFAOD prior to therapy with the requested agent AND
  3. The patient will not be concurrently using another medium chain triglyceride product AND
  4. The patient will not be using the requested agent for more than 35% of the patient’s total prescribed daily caloric intake OR
2. The patient has another FDA labeled indication for the requested agent and route of administration OR
3. The patient has another indication that is supported in compendia for the requested agent and route of administration AND
The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

Compendia Allowed: AHFS, or DrugDex 1 or 2a level of evidence

Renewal Evaluation

Target Agent will be approved when ALL of the following are met:

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
The patient has had clinical benefit with the requested agent AND
If the patient has a diagnosis of LCFAOD, BOTH of the following:
1. The patient will not be concurrently using another medium chain triglyceride product AND
2. The patient will not be using the requested agent for more than 35% of the patient's total prescribed daily caloric intake AND
The prescriber is a specialist in the area of the patient’s diagnosis (e.g. endocrinologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

Commercial _ PS _ Dojolvi__PA _ProgSum_ 01-01-2025