Microneedle patch for treatment of influenza

Unmet Need

Influenza, caused by RNA viruses of the family orthomyxoviridae, infects birds and mammals and spreads worldwide in seasonal epidemics, resulting in the deaths of up to 500,000 people every year and millions in pandemic years. Vaccinations against influenza are usually given as a preventative measure but can be rendered ineffective by mutations in circulating strains. During pandemics, timely distribution of vaccines to large portions of the population is limited by production and distribution. Antiviral drugs can be used to treat and prevent influenza, although current influenza strains have become increasingly resistant towards the market leader oseltamivir (Tamiflu®).

Neuraminidase inhibitors (NIs) like Tamiflu® are the most commonly prescribed class of anti-influenza drugs. However these drugs are very polar and consequently have poor oral bioavailability. Only one NI, oseltamivir, has been developed as an oral drug product. Zanamivir (Relenza®), the only other NI on the market, is administered by inhalation, a less than ideal route of administration. Use of the inhaler device has proven challenging for patients, especially the elderly. Furthermore, this route of administration is contraindicated for patients with respiratory preconditions such as asthma, which make up a large percentage of influenza patients. Even though zanamivir remains highly active against oseltamivir-resistant influenza strains and is believed to be less likely to allow for emergence of resistance, it is for the above reasons that market adoption of Relenza has been poor.

Solution & Benefits

Transdermal delivery systems like patches offer a number of improvements over other delivery systems. In general, transdermal patches:

1. Do not require swallowing, eliminating oral side effects.

2. Allows the drug to directly enter the systemic circulation and avoid any absorption and first-pass barriers a drug might encounter with oral delivery.

3. Avoids skin puncture by syringe needles, eliminating pain and patient visits to a physician.

4. Allows large numbers of patients to be reached through simple dosing and distribution.

Microneedle-enhanced transdermal delivery is an elegant, efficient and painless method for increasing the skin permeation of many drugs, including zanamivir. This system consists of the microneedle component, which will create aqueous channels for the drug to diffuse through and a patch component, which is usually comprised of a hydrogel formulation with optimized salt forms and penetration enhancing excipients, as needed.

Research Status

In 2017, under a two-year, $600,000 grant awarded by the National Institute of Allergy and Infectious Disease, part of the National Institutes of Health, TSRL and F6 optimized formulations of the prototype patches. This research is ongoing as TSRL will receive approximately $3,000,000 over the next three years (until 2022) with the award of a Phase II SBIR grant to scale up supplies for IND-enabling dermatotoxicology studies and complete preclinical data to present to the FDA. We expect microneedle delivery to provide therapeutically efficacious levels of zanamivir to prevent and treat influenza infections in vivo from which we plan to open an Investigational Drug Application.

Easy-Access Treatment for People Suffering from the Flu

Overview & Treatment Options

Overview: Influenza (“the flu”) is an infectious disease caused by RNA viruses that affects birds and mammals. Human influenza A and B viruses cause two seasonal epidemics of disease per year—one per hemisphere—resulting in three to five million severe cases and around 500,000 deaths globally [1]. Although the incidence of flu can vary widely by season, approximately 36,000 deaths and more than 200,000 hospitalizations are directly associated with the flu every year in the United States alone [2]. Current options to prevent and treat the flu include vaccines and antiviral drugs, respectively, and each has its limitations. First, vaccines are only effective against certain strains of the virus with seasonal efficacy ranging between 10% and 60% [3]. Second, vaccines can only be used prophylactically and large portions of the population opt not to get vaccinated. Third, there are cost and accessibility/availability issues, as stocks expire at the end of each season and need to be replenished. A combination of these factors result in poor vaccination coverage, typically less than 50% of the overall population for any given year and even less (<20%) during pandemics. Antiviral drugs, including neuraminidase inhibitors like oseltamivir, are also seeing emerging resistance in seasonal and pandemic flu.

Regulatory Benefits & Market Potential

Potential Regulatory Benefits: Orphan Drug Designation, Fast-Track, Accelerated Review.

Market: The total global market for influenza antivirals—which does not include vaccines—exceeded $1.5 billion USD in 2014, based on worldwide sales of the top two selling drugs Tamiflu® (oseltamivir) and Relenza® (zanamivir). Sales in the United States totaled $800 million in 2014 and grew, on average, more than 25% every year since 2010. Pandemics, seasonal variations, and government stockpiling efforts all affect annual influenza therapeutics sales and make forecasting difficult. We believe, however, a novel influenza therapeutic with a higher potency and superior antiviral resistance profile represents over $500 million/year in sales revenue, driven by government stockpiling.

References:

[1] R. Lozano, "Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systemic analysis for the Global Burden of Disease Study 2010," Lancet, vol. 9859, no. 380, pp. 2095-128, 2012.[2] W. Thompson, E. Weintraub, N. Cox, L. Anderson and K. Fukuda, "Mortality associated with influenza and respiratory syncytial virus in the United States," JAMA, vol. 2, no. 289, pp. 179-86, 2003.[3] Centers for Disease Control and Prevention, "Seasonal Influenza Vaccine Effectiveness, 2005-2015," CDC, 2015.