Effective Date

Date of Origin 

01-01-2025            

01-01-2025

Duvyzat™

(givinostat)

Suspension

Treatment of Duchenne muscular dystrophy (DMD) in patients 6 years of age and older.

1

Duchenne muscular dystrophy (DMD)

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations in the protein dystrophin. DMD is the most common childhood form of muscular dystrophy as well as the most prevalent of the muscular dystrophies. DMD is an X-linked recessive inherited genetic condition primarily affecting males, although females who carry the defective gene may show some symptoms. Prevalence is 15.9 per 100,000 live male births in the US and 19.5 per 100,000 live male births in the UK. Dystrophin is the protein associated with this affected gene and provides structural stability to skeletal muscles. Mutations in this gene, and subsequent lack of dystrophin in muscle fiber, result in a rapidly progressing disease involving muscle degeneration and weakness. Symptom onset is in early childhood and many children lose the ability to walk by early adolescence. Beyond muscle weakness, other symptoms include enlargement of the calf muscles, lumbar lordosis, and eventually cardiomyopathy and poor respiratory function. Until relatively recently, boys with DMD usually did not survive much beyond their teen years. Due to advances in cardiac and respiratory care, life expectancy is increasing and many young adults with DMD are surviving into their early 30s. Currently, there is no cure for DMD, and therapies are supportive in nature. Physical therapy, occupational therapy, respiratory care, speech therapy, braces/wheelchairs/contractures and glucocorticoid therapy are among the most common therapies.(2-4) Dystrophin gene deletion and duplication testing is usually the first confirmatory test.(5) Corticosteroid (glucocorticoids) are the standard of care for DMD, although they remain non-curative. Their use improves muscle strength, improves timed motor function, delays loss of ambulation, improves pulmonary function, reduces the need for scoliosis surgery, delays onset of cardiomyopathy, increases survival, and maintains quality of life. The choice of which glucocorticoid to use depends on cost, formulation, and perceived side-effect profiles.(3,5)

Givinostat is a histone deacetylase (HDAC) inhibitor. It is the first nonsteroidal drug approved to treat patients with all genetic variants of DMD. It works by targeting pathogenic processes to reduce inflammation and loss of muscle.(6)

Efficacy

The effectiveness of givinostat for the treatment of DMD was evaluated in a randomized, double-blind, placebo-controlled 18-month study (Study 1; NCT02851797). A total of 179 male patients with a confirmed diagnosis of DMD were randomized 2:1 to receive either givinostat or placebo using weight-based dosing. The study included patients 6 years of age and older who were ambulatory and on a stable dosage of corticosteroids. The primary endpoint was the change from baseline to month 18 in 4-stair climb (4SC) time for givinostat compared to placebo. The secondary efficacy endpoint was change from baseline to month 18 in physical function as assessed by the North Star Ambulatory Assessment (NSAA). Patients treated with givinostat showed statistically significant less decline in the 4-stair climb compared to placebo (1.25 seconds versus 3.03 seconds for the placebo group). Patients treated with givinostat experienced less worsening on the NSAA compared to placebo; however, this was not statistically significant.(1)

Safety

Givinostat has no boxed warnings or FDA labeled contraindications for use.(1)

The manufacturer recommends obtaining and evaluating baseline platelet counts and triglycerides prior to initiation of givinostat. Givinostat should not be initiated in patients with a platelet count less than 150 x 10^9/L. Platelets and triglycerides should continue to monitored during treatment to determine if dosage modifications are needed.(1)

Additionally, the manufacturer recommends obtaining ECGs in patients with underlying cardiac disease or taking concomitant medications that cause QT prolongation when initiating treatment with givinostat and during concomitant use, and as clinically indicated.(1)

1

Duvyzat prescribing information. Italfarmaco SPA. March 2024.

2

Duchenne muscular dystrophy (DMD). Muscular Dystrophy Association. https://www.mda.org/disease/duchenne-muscular-dystrophy. 

3

Biggar, W. D., Skalsky, A., & McDonald, C. M. (2022). Comparing deflazacort and prednisone in Duchenne Muscular Dystrophy. Journal of Neuromuscular Diseases, 9(4), 463–476. https://doi.org/10.3233/jnd-210776. 

4

U.S. Department of Health and Human Services. Muscular dystrophy. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/health-information/disorders/muscular-dystrophy.

5

Birnkrant, D. J., Bushby, K., Bann, C. M., Apkon, S. D., Blackwell, A., Brumbaugh, D., Case, L. E., Clemens, P. R., Hadjiyannakis, S., Pandya, S., Street, N., Tomezsko, J., Wagner, K. R., Ward, L. M., & Weber, D. R. (2018). Diagnosis and management of Duchenne muscular dystrophy, part 1: Diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. The Lancet Neurology, 17(3), 251–267. https://doi.org/10.1016/s1474-4422(18)30024-3.

6

FDA approves nonsteroidal treatment for Duchenne muscular dystrophy. U.S. Food & Drug Administration. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-nonsteroidal-treatment-duchenne-muscular-dystrophy.

Duvyzat

givinostat hcl oral susp

8.86 MG/ML

M ; N ; O ; Y

N

Duvyzat

givinostat

8.86 MG/ML

3

Bottles

30

DAYS

Duvyzat

givinostat hcl oral susp

8.86 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Duvyzat

givinostat

8.86 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PA

Initial Evaluation

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

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. 1. 1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
      2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
   2.  BOTH of the following:
      1. ONE of the following:
         1. The patient has a diagnosis of Duchenne Muscular Dystrophy confirmed by genetic analysis (i.e., dystrophin deletion or duplication mutation) (genetic test required) AND ONE of the following:
            1. BOTH of the following:
               1. The patient has tried and had an inadequate response after a 6 month duration of therapy with a glucocorticoid used to treat DMD AND
               2. The patient will continue to be on a glucocorticoid while taking the requested agent OR
            2. The patient has an intolerance or hypersensitivity to a glucocorticoid used to treat DMD OR
            3. The patient has an FDA labeled contraindication to all glucocorticoids used to treat DMD OR
         2. 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:
         1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
         2. There is support for the use of the requested agent for the patient’s age for the requested indication AND
2. If the patient is initiating therapy, then ALL of the following:
   1. The patient’s baseline (i.e., prior to therapy with the requested agent) platelet level has been obtained and is greater than or equal to 150 x 10^9/L AND
   2. The patient’s baseline (i.e., prior to therapy with the requested agent) triglyceride levels have been evaluated AND
   3. If the patient has underlying cardiac disease or is taking concomitant medications that cause QT prolongation, ECGs have been obtained AND
3. The patient's platelet levels will continue to be monitored during treatment with the requested agent AND
4. The patient's triglyceride levels will continue to be monitored during treatment with the requested agent AND
5. If the patient has underlying cardiac disease or is taking concomitant medications that cause QT prolongation, ECGs will continue to be monitored as clinically indicated AND
6. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., pediatric neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
7. 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

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

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 improvements or stabilization with the requested agent (e.g., slowed disease progression, improved strength, timed motor function, pulmonary function; reduced need for scoliosis surgery) AND
3. The patient’s platelet level will continue to be monitored during treatment AND
4. The patient’s triglyceride levels will continue to be monitored during treatment AND
5. If the patient has underlying cardiac disease or is taking concomitant medications that cause QT prolongation, ECGs will continue to be monitored as clinically indicated AND
6. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., pediatric neurologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
7. 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.   

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 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

Length of Approval: up to 12 months