About KEVEYIS

Helping to turn limitation into activation

KEVEYIS has been shown to reduce the number, severity, and duration of Primary Periodic Paralysis (PPP) attacks.1,2

KEVEYIS is the first and only FDA-approved treatment for hyperkalemic, hypokalemic, and related variants of PPP1
  • Efficacy: The efficacy of KEVEYIS has been proven in 2 clinical studies1
  • Tolerability: KEVEYIS has a demonstrated safety profile1
  • Oral formulation: KEVEYIS offers patients twice-daily oral dosing1
  • Diagnostic & coding information:
    • ICD-9 Codes: 359.3 (Periodic Paralysis) or 359.29 (Other specified myotonic disorders)
    • ICD-10 Codes: G72.3 (Periodic Paralysis) or G71.19 (Other specified myotonic disorders)
    • KEVEYIS NDC: 71090-001-01

Results in Study 1—Impact on attacks and acute worsening

Study 1 was a 9-week, double-blind, placebo-controlled multicenter study that consisted of 2 substudies—hyperkalemic periodic paralysis (n=21) and hypokalemic periodic paralysis (n=44).1

Primary endpoint: From baseline to week 9, treatment with KEVEYIS decreased weekly attack rates while treatment with placebo resulted in increases2*

*Treatment effect equals KEVEYIS attack rate per week minus placebo attack rate per week; adjusted for missing diary days. Attacks per week (defined as weekly attack rate) was the average number of self-reported attacks of muscle weakness per week. The posttreatment attacks were calculated as the average number of attacks per week over the final 8 weeks of the 9-week double-blind phase. The first week of diary data was excluded to avoid contamination of the efficacy assessment by the participant’s previous treatment, if any.2

†Treatment effect is computed as the median of the bootstrap distribution of treatment group difference in median response. The 95% confidence interval (CI) is computed using the 2.5 and 97.5 percentiles of this bootstrap distribution.2

Decrease in attack rates
Patients treated with KEVEYIS experienced significant decreases in the rate of weekly attacks. In contrast, placebo-treated patients experienced an increase in the rate of weekly attacks.1
Secondary endpoint: From baseline to week 9, there were no episodes of acute worsening with KEVEYIS2*

*Acute worsening was defined as an increase in attack frequency or severity necessitating withdrawal from the initial 9-week treatment period. For the hypokalemic subjects, the proportions of participants reaching the endpoint of acute worsening were compared between the placebo and KEVEYIS groups. Based on the initial pilot trials, it was expected that very few hyperkalemic participants would reach the endpoint; therefore, endpoint data were summarized descriptively for those subjects.2

No acute worsening
Patients treated with KEVEYIS did not experience episodes of acute worsening necessitating withdrawal. In contrast, placebo-treated patients experienced an increase in episodes of acute worsening necessitating withdrawal.1

Results in Study 1—Impact on attack severity and duration

Secondary endpoint: From baseline to week 9, patients treated with KEVEYIS had decreased attack severity compared with placebo2*

*The severity-weighted attack rate was calculated from self-reported scores of attack severity (scored as 1-10 with increasing severity) defined as the sum of average attack severity across all distinct attacks over the final 8 weeks (weeks 2-9) divided by the number of weeks that the patient was followed. Severity-weighted attack data were adjusted for missing diary days.2

Decrease in attack severity
When patients taking KEVEYIS experienced attacks, they were less severe on average than the attacks experienced by patients taking placebo.2
Secondary endpoint: From baseline to week 9, KEVEYIS reduced the duration of weekly attacks compared with placebo2*

*The weekly attack duration was calculated from self-reported attack duration across all distinct attacks over the final 8 weeks (weeks 2-9) divided by the number of weeks that the patient was followed. Weekly attack duration was adjusted for missing diary days.2

Reduction in the duration of weekly attacks
When patients taking KEVEYIS experienced attacks, they were of shorter duration on average than the attacks experienced by patients taking placebo.2

Results in Study 2—Improvements in hyperkalemic and hypokalemic patients

Study 2 was a 35-week, double-blind, placebo-controlled, multicenter, two-period crossover study that consisted of 2 substudies: patients diagnosed with hypokalemic periodic paralysis (n=42) and those with hyperkalemic periodic paralysis (n=31).1

Primary Endpoint: The majority of patients who experienced an intolerable increase in attack frequency or severity necessitating withdrawal from the treatment were treated with placebo3*

*In the hypokalemic substudy, the primary outcome variable was the occurrence of an intolerable increase in attack frequency or severity (defined as necessitating withdrawal from the treatment phase). Of the 42 patients enrolled in the hypokalemic substudy, 34 completed both treatment phases. However, only 15 of the 34 reached the endpoint of intolerable worsening while in one or both treatment phases.3

Majority reached acute worsening in placebo phase
Of the 15 patients who experienced an intolerable increase in attack severity or frequency necessitating withdrawal, 11 reached this endpoint while taking placebo versus 2 while taking KEVEYIS.3
Primary Endpoint: From baseline to week 9, there were significantly fewer attacks when patients were treated with KEVEYIS3*


*Attack rate per week over the final 8 weeks of each phase (defined as attack rate) was the primary efficacy outcome in the hyperkalemic substudy.3

Decrease in attack rates
Patients treated with KEVEYIS experienced a significantly decreased weekly attack rate, with 2.3 fewer attacks, compared to when they were taking placebo (P=0.006).3

A demonstrated tolerability profile

The most common adverse reactions in patients treated with KEVEYIS (incidence ≥10% and rates greater than placebo) were paresthesia, cognitive disorder, dysgeusia, and confusional state (KEVEYIS n=36; placebo n=29).1

*Cognitive disorder combined cases with the preferred terms of cognitive disorder, disturbance in attention, and mental impairment.1

The majority of patients completed the pivotal trial (Study 1)2

In the double-blind phase:

None of the hyperkalemic or hypokalemic patients treated with placebo withdrew due to an adverse reaction.2

An oral medication with twice-daily dosing1

Dosing Guidelines
Initial Dose
Dose Increase
Dose Decrease
  • The recommended starting dose of KEVEYIS is 50 mg twice daily
  • The dose may be increased based on individual response at weekly intervals
  • The maximum recommended total daily dose is 200 mg
  • The dose may be decreased at weekly intervals (or sooner in case of adverse reactions)

Evaluate the patient’s response to KEVEYIS after 2 months of treatment

Dose adjustment based on individual response may be helpful in managing adverse reactions.1

Primary Periodic Paralysis is a complex and challenging disorder. Learn more about its diagnosis and management.

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INDICATION

KEVEYIS is indicated for the treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

  • Hypersensitivity to dichlorphenamide or other sulfonamides
  • Concomitant use of KEVEYIS and high-dose aspirin
  • Severe pulmonary disease, limiting compensation to metabolic acidosis caused by KEVEYIS
  • Hepatic insufficiency: KEVEYIS may aggravate hepatic encephalopathy

WARNINGS AND PRECAUTIONS

Hypersensitivity/Anaphylaxis/Idiosyncratic Reactions

  • Fatalities associated with the administration of sulfonamides have occurred due to adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias
  • Pulmonary involvement can occur in isolation or as part of a systemic reaction
  • Discontinue KEVEYIS at the first appearance of skin rash or any sign of immune-mediated or idiosyncratic adverse reaction

Concomitant Use of Aspirin

  • Anorexia, tachypnea, lethargy, and coma have been reported with concomitant use of dichlorphenamide and high-dose aspirin
  • The concomitant use of KEVEYIS and high-dose aspirin is contraindicated
  • Use with caution in patients receiving low-dose aspirin

Hypokalemia

  • KEVEYIS increases potassium excretion and can cause hypokalemia
  • The risk of hypokalemia is greater when KEVEYIS is used in patients with conditions associated with hypokalemia (eg, adrenocortical insufficiency, hyperchloremic metabolic acidosis, or respiratory acidosis), and in patients receiving other drugs that may cause hypokalemia (eg, loop diuretics, thiazide diuretics, laxatives, antifungals, penicillin, and theophylline)
  • Baseline and periodic measurements of serum potassium are recommended
  • If hypokalemia develops or persists, consider reducing the dose or discontinuing KEVEYIS

Metabolic Acidosis

  • KEVEYIS can cause hyperchloremic non–anion gap metabolic acidosis
  • Concomitant use of KEVEYIS with other drugs that cause metabolic acidosis may increase the severity of metabolic acidosis
  • Baseline and periodic measurements of serum bicarbonate are recommended
  • If metabolic acidosis develops or persists, consider reducing the dose or discontinuing KEVEYIS

Falls

  • KEVEYIS increases the risk of falls; risk is greater in the elderly and with higher doses
  • Consider dose reduction or discontinuation of KEVEYIS in patients who experience falls while treated with KEVEYIS

PREGNANCY AND LACTATION

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known in humans whether dichlorphenamide is excreted in human milk; exercise caution when administered to a nursing woman.

ADVERSE REACTIONS

The most common adverse reactions seen in clinical trials (incidence ≥ 10% and greater than placebo) include paresthesias, cognitive disorder, dysgeusia, and confusional state.

References

  1. KEVEYIS [package insert]. Feasterville-Trevose, PA: Strongbridge Biopharma; 2017.
  2. Sansone VA, Burge J, McDermott MP, et al; for the Muscle Study Group. Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis. Neurology. 2016;86:1408-1416.
  3. Tawil R, McDermott MP, Brown R, et al. Randomized trials of dichlorphenamide in the periodic paralyses. Ann Neurol. 2000;47:46-53.