Policy & Regulation
Ligand and SQ Innovation Enter into Exclusive Worldwide Captisol License and Supply Agreements for High-Concentration Furosemide Formulation
10 July 2019 - - US-based drugmaker Ligand Pharmaceuticals Inc. (NASDAQ: LGND) and Switzerland-based SQ Innovation AG have entered into long-term, exclusive commercial license and supply agreements for use of Ligand's Captisol technology in the formulation of high-concentration furosemide for the treatment of edema in patients with heart failure, the companies said.
SQ Innovation is developing a novel drug-device combination for cost-effective subcutaneous delivery of diuretics that currently require intravenous administration by a certified healthcare professional.
Ligand is eligible to receive potential milestone payments and royalties, as well as revenue from materials sales of Captisol.
Heart failure is a common, complex and serious condition affecting approximately 6.2m people in the US and 26m people worldwide. Many patients with heart failure experience episodes of worsening symptoms due to fluid overload.
Current therapy options for these episodes include an increase in oral medication or, when oral treatment is not sufficiently effective, intravenous treatment, typically delivered in an emergency room or hospital.
Subcutaneous infusion by means of a mini pump adhered to the skin may offer a solution for patients who otherwise do not require hospital care.
Fluid overload in heart failure is responsible for approximately USD 14bn in Medicare spending, or approximately 3.9% of the Medicare budget, making it one of the most expensive therapies for the elderly.
The high spending is attributable to in-patient care for diuretic treatment which accounts for approximately 7% of Medicare hospital admissions.
In addition, a hospital stay is associated with risks of adverse outcomes due to rapid muscle loss and functional decline experienced by many elderly patients during their hospital stay and recovery.
Furosemide is the leading diuretic used in patients with heart failure. It is administered as a daily oral therapy in most patients with heart failure, and intravenously in the hospital when oral medicine is insufficient to reduce fluid overload.
Furosemide is poorly soluble, particularly at the neutral pH level required for subcutaneous delivery.
Until now furosemide products suitable for human use have a low concentration and require 8-10mL to deliver the common therapeutic dose of 80mg. Although delivery of 8-10mL of fluids is possible in principle, there is currently no FDA-approved product in a drug cartridge or delivered by a patch pump with a volume greater than 3.5mL.
SQ Innovation's objective is to develop cost-effective therapies for the treatment of edema and other conditions where and when needed for patients who otherwise do not need to be in a hospital or emergency room.
Instead of developing a drug container and device that accommodates a low-concentration drug, SQ Innovation conducted formulation research that led to the filing of multiple patent applications in 2018 and 2019.
The broad formulation research program included a range of potential methods to improve the solubility of loop diuretics at neutral pH. This research revealed that beta-cyclodextrins, particularly the proprietary beta-cyclodextrin Captisol, enabled a high concentration of furosemide at neutral pH.
This allowed 80mg of furosemide to be delivered using less than 3mL of drug formulation. SQ Innovation owns patent applications related to the use of cyclodextrins with loop diuretics that, when issued, would provide patent protection through 2039.
Additionally, this formulation is subject to patents issued to Ligand subsidiary CyDex Pharmaceuticals regarding its Captisol product and technology that provide patent protection through 2034.
SQ Innovation is a privately-held Swiss biopharmaceutical company located in Zug, Switzerland, and Burlington, MA, that was established to develop and commercialise innovative cost-effective therapies for subcutaneous delivery of pharmaceutical products where and when needed.
Its first product, for the treatment of fluid overload (edema) in patients with heart failure, is currently under development following a plan that has been reviewed with the US-FDA.
The novel combination product is based on the Sensile Medical micro-pump technology and its small-volume cartridge-based platform.
The device design uses a reusable motorized component and disposable cartridge, which minimizes waste and creates cost-effective treatment options in numerous therapy areas, including treatment of edema in heart failure. The products are subject to regulatory review and approval.
Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs.
Captisol was invented and initially developed by scientists in the laboratories of Dr. Valentino Stella, University Distinguished Professor at the University of Kansas' Higuchi Biosciences Center, for specific use in drug development and formulation.
This unique technology has enabled several FDA-approved products, including Amgen's Kyprolis, Baxter International's Nexterone, Acrotech Biopharma's Evomela, Melinta Therapeutics' Baxdela, Sage Therapeutics' Zulresso, Merck and Co.'s Noxafil and Pfizer's Vfend. There are many Captisol-enabled products currently in various stages of development.
Ligand is a biopharmaceutical company focused on developing or acquiring technologies that help pharmaceutical companies discover and develop medicines.