Vernakalant

Vernakalant (INN; codenamed RSD1235, proposed tradenames Kynapid and Brinavess) is an investigational drug under regulatory review for the acute conversion of atrial fibrillation. It was initially developed by Cardiome Pharma, and the intravenous formulation was bought for further development by Merck in April 2009.[1] In September 2012, Merck terminated its agreements with Cardiome and has consequently returned all rights of the drug back to Cardiome, which as of 2018 is known as Correvio Pharma.

Vernakalant
Clinical data
License data
Routes of
administration		Intravenous, oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.121.790
Chemical and physical data
FormulaC20H31NO4
Molar mass349.464 g/mol g·mol−1
3D model (JSmol)
 NY (what is this?)  (verify)

On 11 December 2007, the Cardiovascular and Renal Drugs Advisory Committee of the US Food and Drug Administration (FDA) voted to recommend the approval of vernakalant,[2] but in August 2008 the FDA judged that additional information was necessary for approval.[1] The drug (under brand name Brinavess) was approved in Europe on 1 September 2010.[3]

An oral formulation underwent Phase II clinical trials between 2005 and 2008.[4][5]

On 10 December 2019 the resubmitted New Drug Application for vernakalant was discussed by the Cardiovascular and Renal Drugs Advisory Committee Meeting of the US Food and Drug Administration (FDA). [6] The Advisory Committee voted not to recommend the approval of vernakalant for the rapid conversion of recent onset atrial fibrillation.[7]

Mechanism of action

Like other class III antiarrhythmics, vernakalant blocks atrial potassium channels, thereby prolonging repolarization. It differs from typical class III agents by blocking a certain type of potassium channel, the cardiac transient outward potassium current, with increased potency as the heart rate increases. This means that it is more effective at high heart rates, while other class III agents tend to lose effectiveness under these circumstances. It also slightly blocks the hERG potassium channel, leading to a prolonged QT interval. This may theoretically increase the risk of ventricular tachycardia, though this does not seem to be clinically relevant.[8]

The drug also blocks atrial sodium channels.[8]

It's mainly used for rapid conversion of acute-onset AF (AF lasting 3 to 72 hours)

Metabolism

Vernakalant is cleared by both renal and hepatic mechanisms. Majority via cytochrome CYP2D6 and excreted as glucuronide. Elimination half life is 3-4 hours.

References
  1. "Merck and Cardiome Pharma Sign License Agreement for Vernakalant, an Investigational Drug for Treatment of Atrial Fibrillation". FierceBiotech. 9 April 2009. Retrieved 12 October 2010.
  2. "FDA Advisory Committee Recommends Approval of Kynapid for Acute Atrial Fibrillation". Drugs.com. Retrieved 15 March 2008.
  3. "BRINAVESS (vernakalant) for Infusion Approved in the European Union for Rapid Conversion of Recent Onset Atrial Fibrillation" (Press release). Merck & Co., Inc. 1 September 2010. Archived from the original on 28 September 2010. Retrieved 28 September 2010.
  4. Clinical trial number NCT00267930 for "Study of RSD1235-SR for the Prevention of Atrial Fibrillation/Atrial Flutter Recurrence" at ClinicalTrials.gov
  5. Clinical trial number NCT00526136 for "Vernakalant (Oral) Prevention of Atrial Fibrillation Recurrence Post-Conversion Study" at ClinicalTrials.gov
  6. "December 10, 2019 Meeting of the Cardiovascular and Renal Drugs Advisory Committee Meeting Announcement". FDA.gov. Retrieved 9 December 2019.
  7. "FDA Panel Shoots Down Afib Cardioversion Drug Over Safety". MedPage Today. Retrieved 11 December 2019.
  8. Miki Finnin, Vernakalant: A Novel Agent for the Termination of Atrial Fibrillation: Pharmacology, Medscape Today, retrieved 12 October 2010
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