Portable Transdermal Acoustic Patch for Delivery of Large Molecules to Improve HIV Patient Medication Regime Compliance by Elimination of Side Effects Including Injection Site Reactions

DESCRIPTION provided by applicant This Phase IIB SBIR finalizes development conducts in depth preclinical testing and completes Verification and Validation of the Portable Transdermal Acoustic Patch TAP for Delivery of Large Molecules to Improve HIV Patient Medication Regime Compliance by Elimination of Side Effects Including Injection Site Reactions Nearly million people worldwide are living with HIV with roughly million in North America and Western and Central Europe The main treatment approach for HIV is Highly Active Antiretroviral Therapy which uses multiple medications to arrest viral replication HIV medication regimens must be taken with near perfect compliance to maximize benefits and prevent the development of viral resistance If the HIV virus becomes resistant to treatment salvage drugs such as the fusion inhibitor T must be tried While T is very effective a major side effect additional to injection pain is an injection site reaction ISR which is experienced by of patients and reduced the rate of adherence of prescribed doses of patients in one clinical study to despite the risks of poor compliance A method to deliver antiretrovirals without adverse side effects is needed as well as a low cost simple delivery approach usable in developing nations TAP uses kHz ultrasonic waves to gently open micro channels in the skinandapos s stratum corneum enabling large molecule andgt Da medications like T to reach the blood system TAP is designed to operate at low acoustic intensity levels mW cm that do not cause significant skin changes TAP is a platform technology that delivers large molecule drugs such as broadly neutralizing antibodies novel entry inhibitors and T without the ISR leading to greater patient compliance and positive therapeutic clinical outcomes The Phase II project met the Specific Aims demonstrating that T could be delivered at clinically comparable doses without causing skin damage in a day porcine study N The Phase IIB will determine the dose linearity of T delivered transdermally and demonstrate delivery of a clinical dose g mL of T at three differet anatomical regions skin thicknesses in an in vivo porcine model Phase IIB Specific Aims Aim TAP design and T activity verified Months Acceptance Criteria T maintains HIV antiviral activity in vitro after min ultrasound application pandlt where applicable Active Patches and Control Boxes pass Verification tests a Performance b Safety including IEC c Shipping vibration and d Reliability and Lifetime Subjects pass Usability Aim Optimized dosing and treatment achieve clinical T plasma levels Months Acceptance Criteria TAP Beta II treatment duration and T dosage determined that produce T Ctrough levels of at least g mL in porcine model after one week of treatment Aim Porcine skin study towards FDA Investigational Device Exemption Months Acceptance Criteria Demonstrate sufficient T bioavailability Ctrough g mL is achieved with optimal treatment parameters for porcine skin in vivo at different anatomical regions PUBLIC HEALTH RELEVANCE Approximately million people worldwide are living with HIV The only FDA approved HIV fusion inhibitor is T which is highly effective but causes injection site reactions in of patients and has been severe enough to result in patient non compliance rates above This SBIR Phase IIB Competing Renewal grant finalizes development of the Transdermal Acoustic Patch TAP a device that enables large molecule medications including medications that cannot be delivered orally to be delivered through the skin by gently opening temporary micro channels in the outer skin barrier Highly effective medications like T or broadly neutralizing antibodies for HIV that are on the horizon can be delivered painlessly and reliably improving compliance and outcomes and reducing hospitalization costs The transdermal platform can be applied for other for other conditions and diseases