Solvent-Free Amiodarone Injection

In 2001, CyDex (now Ligand) began development of Amiodarone HCL, brand name Cordarone^® I.V. This work led to a Patent being granted in 2005 and in 2006, CyDex licensed Captisol to Prism.

Cordarone I.V. is an FDA-approved drug that prolongs the duration of the action potential of all cardiac fibers while causing minimal reduction of dV/dt (maximal upstroke velocity of the action potential).

Cordarone I.V. Side-Effects and Incompatibilities

• PolySorbate 80 (or Tween 80)
• Hepatotoxicity, severe hypotension, cardiac depression
• BzAlcohol: CNS depression, acidosis, respiratory failure
• Foams –complicating required dilution and delivery
• Irritating, phlebitis
• Incompatible with plastics 

Goal of Program

• Eliminate undesirable excipients
• Reduce side-effects
• 505b2 filing with bioequivalence bridging data, i.e. pharmacodynamics and pharmacokinetics required in 80-120% range 

Captisol-enabled^® Results

View Graph

• Study showing amiodarone plasma concentration-time profile along with its major metabolite, desethylamiodarone
• Comparison study in normal: PM101 (Captisol-enabled^® Amiodarone) vs AIV (existing commercial product).
• Study demonstrates bioequivalence in same concentration in plasma with Captisol-enabled^® Amiodarone compared to Cordarone I.V.
• No change in pharmacodynamics and PK
• Captisol-enabled^® 100% of pharmacodynamics and pharmacokinetics required for 5052b filin 

• Captisol^® replaced polysorbate 80, thereby alleviating blood pressure changes due to this co-solvent
• A study of Captisol-enabled^® Amiodarone demonstrated no changes in blood pressure

In 2008, Prism received approval for Amiodarone (Nexterone) in a vial presentation. Prism's initial submission supported vial and syringe presentations 

In 2010, Prism received approval for an sNDA for a pre-mixed bag or ready-to-use bag presentation

• Faster
• Easier administration
• Time saver in emergency room setting
• Cost saver

Then, in 2011, Baxter acquired Prism Pharmaceuticals and the Nexterone^® product line. The deal included upfront and milestones fees that could potentially total up to $338M.