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
- 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
- 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.
Interested In Partnering?
Contact us today and take the first step to a great partnership.