As the US faces an epidemic of opioid abuse, fentanyl transdermal patches have become a drug of choice for recreational drug abusers, due to the drug’s potency and its ease of abuse by the oral route. 4P Therapeutics has developed the Defent™ abuse deterrent patch technology to deter abuse of fentanyl patches by the oral, buccal & inhaled routes, which represent as much as 70% of all transdermal fentanyl abuse. The technology is based on controlled release of taste aversive agents incorporated into the patch. Taste aversion has several advantages, such as its high potency, established safety, and the potential to prevent accidental misuse by children & pets. The controlled release aspect of the technology ensures that the abuse deterrent properties are maintained after normal use and during attempts to separate the aversive agents from the fentanyl.
In Defent™, the aversive agents are encapsulated in a controlled-release matrix and coated onto the backing of a transdermal fentanyl patch. This ensures maximum exposure during oral abuse and during attempts to extract the drug, while preventing exposure of the patient to the aversive agents during transdermal wear. A key differentiating aspect of the technology is that the aversive agents are isolated from the drug matrix, meaning that the approved drug matrix does not have to be modified. As a result, development risk is minimized and development resources are significantly reduced.
In addition to the fentanyl patch, this technology has broad applicability to any therapeutic patch where deterring abuse and accidental misuse by children and pets are valuable attributes.
Transderm-Scop® was the first transdermal product approved by the FDA (1979). It is indicated for the treatment of nausea and vomiting associated with motion sickness and recovery from anesthesia and surgery. 4P Therapeutics is developing an improved proprietary generic scopolamine patch. Product improvements include enhancements to the manufacturing processes to reduce the manufacturing cost and optimization of the adhesive formulation to reduce cold flow and increase patient acceptability. Development of the 4P improved generic scopolamine transdermal patch will leverage 4P’s efficient screening model to develop a bioequivalent patch formulation in vitro and confirm equivalence in a pilot bioequivalence clinical trial. Once the formulation has been confirmed, a commercial manufacturing process will be developed and pivotal clinical studies (bioequivalence, adhesion, sensitization) will be performed to support ANDA submission.
Follicle stimulating hormone (FSH) is indicated for the treatment of infertility in women. Normally FSH is given in the form of daily subcutaneous injections. 4P Therapeutics is developing a novel transdermal patch to match the pharmacokinetic profile of FSH subcutaneous injection. Elimination of injections during FSH therapy is a key attribute desired by patients. The 4P FSH patch is designed to offer a painless, easy to use one-step application to improve patient compliance with FSH therapy. In addition to improved patient compliance, the need for sharps disposal is eliminated. The 4P patch will be submitted utilizing the 505(b)(2) NDA development pathway, incorporating a Phase I clinical stage in order to optimize the system configuration and match SC injection and a Phase 3 pivotal clinical trial to demonstrate noninferiority against the reference listed drug.
Exenatide (exendin-4) is a GLP-1 receptor agonist which regulates glucose and insulin levels. For treatment of Type 2 diabetes, exenatide is currently administered as twice-daily subcutaneous injections (Byetta®) or as a once-weekly (Bydureon®) injection. However, many patients have a strong aversion to needles, and struggle with compliance with injection therapies. Injection therapy is such a big issue for patients that it has been reported that 10-20% of diabetics would forego 10 years of life in perfect health in order to avoid multiple daily injections.
4P Therapeutics is developing a transdermal patch for administration of exenatide to match the pharmacokinetic profile of subcutaneous injections of exenatide. In addition to being needle-free, painless, and easy-to-use, the 4P transdermal exenatide system can incorporate compliance tracking to help providers improve patient outcomes. The development of a twice-daily exenatide patch matching the profile of exenatide injections offers a straightforward pathway to 505(b)(2) NDA approval. Additionally, 4P has extensive experience in controlled release formulations, which offer the potential for once-daily or sustained transdermal delivery systems incorporating exenatide.