The Challenge:
Infantile spasms is a severe type of pediatric epilepsy that impact more than 1,200 infants per year in the U.S. It usually begins between 1-2 months and peaks between 4-8 months of age. Most babies grow out of them by the age of 2 to 4 years. If untreated or poorly treated, the disorder results in serious brain damage, resulting in loss of brain development, loss of social interactions, and significantly lower cognition. If diagnosed early and treated promptly, then the infant can develop normally.
The standard treatment of infantile spasm is vigabatrin (VGB), which is very unstable once dissolved and diluted in water. As such, the parent or guardian must prepare VGB prior to every administration, a process that requires 15 steps which includes dissolving the powder, diluting it with the correct amount of water, and administering the correct dose to the infant. The resulting VGB solution is very bitter, often resulting in the infant spitting out some to most of the dose, leaving the caregiver to estimate how much was spit out and administer an additional amount. If insufficient VGB is administered, the infant risks experiencing symptoms. However, administering too much VGB induces retinal toxicity, which is manifested by visual field loss and eventually blindness. Irreversible visual field constriction occurs in 34% of children treated with VGB.
Pyros Pharmaceuticals, Inc. (Pyros) set out to develop and commercialize a ready-to-use, pre-mixed flavored VGB formulation that would ensure a streamlined process for the caregivers. Securing patent rights on a novel formulation of a known drug is a difficult proposition, especially when the formulation contains known components. The resulting lack of exclusivity can hamper commercialization of the new formulation, even though it has advantages over the current treatment.
The Solution:
Licensing Patent Rights: Pyros identified a PCT patent application describing pharmaceuticals for oral dosage for seven drugs, one of which was VGB, and the patent owners indicated that the patent application was available for licensing. AP&S was retained to help with the transactional and intellectual property representation.
A review of the PCT patent application revealed that the relevant formulations comprised VGB, a known patented drug, and well-known components (e.g., preservatives, buffering agents, sweetener, and flavoring agents). It was determined that the pending claims were not patentable over the prior art. The patent owners were provided an opportunity to provide a patentable claim set. The revised claim set, although narrower in scope, was also determined to be unpatentable over the prior art. Moreover, a review of the patent family indicated that PCT patent application entered the national stage only in the United States; there were no foreign patent rights available. Even with these issues, Pyros was still interested in pursuing a License Agreement.
AP&S minimized the risk for Pyros by limiting the field of use to VGB and structuring an escalating compensation based four patenting scenarios, with the lowest compensation where neither party are able secure patents and the highest compensation where both parties obtain patents on the new formulation. The License Agreement further ceded control of patent prosecution to Pyros’ patent counsel.
Securing Licensed Patents: Upon becoming the representative on the US licensed patent application, AP&S filed claims that addressed the prior art impediments and were able to secure a US patent that contained claims specifically covering the novel formulation being commercialized by Pyros (US PAT No 12,016,857).
Pyros Patents Rights: Reviewing the development of the formulation by Pyros, AP&S identified a pathway to secure new patent rights for the company, which would also help secure international patent protection not available with the licensed patent rights. The Written Opinion issued in the Patent Cooperation Treaty (PCT) application (published as WO2024058812A1) determined that the claims were novel and inventive over the prior art, a strong presumption of patentability.
Trademark Rights: AP&S assisted Pyros with clearance searches and identified seven potential registerable trademarks. Applications were filed and approved in the US and Europe. Pyros selected Vigafyde™ as the trademark for their ready-to-use, pre-mixed flavored VGB formulation and VIGPODER™ for the equivalent powder formulation.
The Result:
On June 17, 2024, the FDA approved the orphan drug status and the name of Pyros’ Vigafyde™, as monotherapy for the treatment of infantile spasms in pediatric patients 1 month to 2 years of age for whom the potential benefits outweigh the potential risk of vision loss. The orphan drug status provided Pyros seven years of exclusivity. The patent rights secured by AP&S extended the exclusivity period to 20 years for Pyros’ ready-to-use, pre-mixed flavored VGB formulation.
Upsher-Smith, a competitor that was commercializing a powder and a tablet form of VGB under the name Vigadrone®, filed oppositions to the seven Pyros published trademarks in both the US and Europe. However, when assessing the strength of Pyros’ trademark and patent rights along with the advantages of a ready-to-use, pre-mixed flavored VGB formulation for administration to infants, the parent company of Upsher-Smith, Bora Pharmaceuticals, chose to acquire Pyros rather than enter into protracted trademark oppositions with uncertain outcomes. In the press release, Michael Smith, co-founder and CEO of Pyros stated, “We are excited to reach this agreement with Bora, a company that shares our commitment to supporting families navigating the unique challenges of rare diseases and aligns with our mission of elevating the standard of care for these often overlooked and under-supported patient communities.”[1]
VIGAFYDE™ is the first and only ready-to-use vigabatrin oral solution and represents a significant advancement in the treatment of infantile spasms as the first new product approved for this condition in 15 years. Indeed, a recent study demonstrated that both naïve and experienced caregivers delivered significantly more accurate and less variable doses of the ready-to-use VIGAFYDE™solution compared to solutions prepared from VGB powders for oral solution.[2]
[1] https://bora-corp.com/bora-pharmaceuticals-to-expand-rare-disease-portfolio-with-acquisition-of-us-based-pyros-pharmaceuticals/