Are long-acting injectable medications the future of long-term medication in animals?

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There are several challenging aspects of care of pets with chronic disease, some of which include gaining and maintaining long-term client compliance and adherence as well as navigating chronic caregiver burden in pet parents. These problems are especially obvious in clients with cats with chronic conditions like hyperthyroidism and osteoarthritis that require daily medication. Administering long term medications can be next to impossible for elderly and disabled people. However, biodegradable polymer based long-acting injectable medication (LAI), might be an innovative solution that can replace daily medication dosing.

LAI overview

I recently interviewed Kamalesh Rao, MS, founder and CEO of Lifescient, a clinical researcher with over 25 years of experience in developing human pharmaceuticals to learn more about this technology. One of the products he helped develop is Probuphine, a buprenorphine subdermal long-acting injectable medication used to treat those suffering with an opioid addiction. The release of buprenorphine from Probuphine in humans results in continuous drug delivery maintaining a stable blood level of medication for days to months following a single subcutaneous injection.

Since the polymer matrix of Probuphine is non-biodegradable, the spent matrix shell must be removed before the subsequent treatment is administered. Another example of LAIs in humans is the birth control implants in women, Nexplanon. LAIs provide continuous drug delivery while maintaining a stable blood level of medication for days to months following a simple placement procedure.

Now, Rao is developing a long-acting injectable drug delivery platform for animals that will release medication from a biodegradable matrix that is safely absorbed by the body so there is no removal required after the medication is exhausted. The focus is on addressing chronic conditions in animals, with a particular focus on the development of medications for cats. Furthermore, this proprietary platform technology can be used to reformulate several medications for use across multiple species of animals, both in the companion animal market as well as large animal and exotics.

The benefits of using an LAI versus traditional daily dosing include:

• Guarantee prescription compliance and adherence
• Decrease caregiver burden
• Increase medication bioavailability leading to lower doses of medication than with tablets
• Minimize side effects due to maintenance of the drug within the optimal therapeutic window
• Decrease medication problems associated with client error
• Decrease clinic time and man-power spent explaining how to give your pet a pill
• Greater comfort to pets, more pets treated appropriately for chronic disease, and improved overall quality of care
• LAIs are abuse deterrent and minimize drug diversion

LAI medications developed by Lifescient are depot formulations. The medication is stored in a biocompatible and biodegradable polymer matrix. The depot stays in the body and slowly releases medication over time, and then is safely broken down and absorbed. In the event of non-tolerance, the depot can be removed, unlike other LAIs on the market.

Other factors that make depot LAI formulations superior include:

• Reduced risk of side effects: depot LAIs are designed to release medication slowly, which can help minimize the risk of side effects associated with rapid drug absorption or peak drug levels.
• Improved convenience and compliance: Because of their longer duration of action compared to the currently available LAI medications, depot LAIs can be more convenient because the frequency of medication administration is decreased.
• More precise dosing: Depot LAIs provide a more precise, controlled dose of medication than microsphere/nanosphere technologies.

The packaging and administration of an LAI is like a microchip – a preloaded disposable syringe. Sedation of animals is not required, though the practitioner may elect to use a local anesthetic depending on the client. The maximum size of an implant would be 2.5x25 mm, however, most veterinary LAIs would be smaller.

Potential benefits of LAIs

When you factor in the benefits of LAI over oral dosing, the overall cost is expected to be lower than a comparable tablet. Surveys of veterinarians conducted by Lifescient thus far have demonstrated that they would be comfortable charging a premium of 20-50% over the alternate treatment options.

The company has developed several prototypes and the technical feasibility of the drug delivery platform has been established. In addition, Lifescient has identified a portfolio of medications that would serve veterinary medicine better than the existing alternatives such as oral tablets, short-term injections and transdermal dosage forms.

The next step will be to apply this technology to an analgesic medication for the treatment of bone cancer pain in dogs. To provide effective long-term pain relief for dogs with bone cancer, drug plasma levels must be maintained within the therapeutic window for an extended period. Currently, the company has submitted a request to the FDA to open an Investigational New Animal Drug (INAD) application file that will allow the start of safety and effectiveness studies, which begins the new drug development and approval process. The knowledge gained from this research and development will be used to apply this platform toward the reformulation of medications to treat other conditions.

In conclusion

The company also needs feedback from the veterinary community to inform them about preferred treatment options and conditions that would be best served by long-acting injectables. This information will allow the company to target the areas where the greatest benefit can be offered to the patient. Additionally, veterinary professionals are also in the best position to inform Lifescient about the price that their clients are willing to pay for the convenience of LAIs.

“Your company’s long-acting medication implants are a very interesting concept. As a feline-only veterinarian, I feel like I spend half of my time figuring out how to get chronic medications into cats. If you are ever doing clinical trials with owned pets, please keep the Cat Clinic of Lawrence in mind as a test site,” expressed Jennifer O’Driscoll, DVM, Cat Clinic of Lawrence, a survey respondent.

To give your feedback and help bring this technology to market sooner, veterinary professionals can help by filling out a survey located at https://survey.zohopublic.com/zs/iZBUWk

Sarah J. Wooten, DVM, graduated from the University of California, Davis School of Veterinary Medicine in 2002. A member of the American Society of Veterinary Journalists, she divides her professional time among small animal practice in Greeley, Colorado; public speaking on associate issues, leadership, and client communication; and writing. She enjoys camping with her family, skiing, scuba diving, and participating in triathlons.