Many patients have difficulty taking the tablet form of a marketed safe and effective antibiotic. Doctors are often hesitant to use the next option in the queue. Appili is planning to address this issue with ATI-1501, a proprietary taste-masked liquid suspension reformulation of metronidazole.
Metronidazole is a widely used front-line oral treatment with over 10 million prescriptions written in the United States every year. It is used to treat parasitic and anaerobic bacterial infections, which heavily burden elderly patients.
Unfortunately, a sizeable and growing number of patients have difficulty taking the tablet form of the drug, which is the only approved oral form on the U.S. market. These patients include children and the elderly, and others who have difficulty swallowing (also known as dysphagia). For these patients, tablets are often crushed and resuspended in food or drink in an attempt to mask the taste and facilitate ingestion.
This approach has many limitations:
The resuspension process often incurs additional costs and increases the potential for dosing errors.
Critically, it is also ineffective at taste masking; metronidazole crushed and resuspended in food remains among the worst tasting antibiotics on market.
Reduced adherence has been linked to increased rates of treatment failure, infection recurrence, and antibiotic resistance. For patients, this can lead to protracted, worsening illnesses and increased potential for infecting others. It can also increase the burden on the caregivers who support these patients.
(2), (3), (4)
If a patient fails on metronidazole, physicians often switch to another class of antibiotics. Healthcare practitioners must limit the use of second- and third-line antibiotic options:
These antibiotics are typically more expensive, and limiting their use helps insurers manage healthcare costs.
The more powerful antibiotics are typically held in reserve to minimize resistance development, a paradigm referred to as ‘stewardship.’ If used indiscriminately, many antibiotics that are effective today could quickly be undermined by increasingly resistant disease.
The bitter taste of metronidazole and lack of appropriate dosage forms for patients with difficulty swallowing presents treatment compliance challenges, which ultimately can lead to detrimental effects on patient outcomes, healthcare costs, infection control, and antibiotic resistance.
Appili aims to fill this significant gap in the treatment paradigm with a taste-masked liquid suspension. ATI-1501 is designed to enable broader use of metronidazole among patients with difficulty swallowing. Our goal is to provide a solution with the same safety and efficacy profile provided by metronidazole for 50 years, that is both easy to swallow and good tasting, thereby helping patients to adhere with their medication and improve their prognoses.
Being able to increase the number of patients who can benefit from this safe, effective, and widely used front-line antibiotic would ultimately support healthcare cost containment and antibiotic stewardship initiatives.
Appili has conducted extensive work to engage healthcare providers and payers to understand the market and competition, and to get direct feedback on adherence, pricing, and reimbursement issues. Our goal is to help patients and their healthcare providers address a significant unmet medical need, while ensuring broad market access, and the potential for our investors to realize the value of this asset.
Our current focus is on partnering the U.S. rights for the program, and next steps include our partner filing a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) following the 505(b)(2) regulatory pathway. We have already met with the FDA, completed clinical studies to support regulatory approval, and are conducting commercial manufacturing activities to support this goal.
(1) IQVIATM 2014-2017 NPA, ‘metronidazole’; IQVIATM 2016-2017 CDM, ‘metronidazole’
(2) Baguley (2012) Arch Dis Child: Prescribing for children - taste and palatability affect adherence to antibiotics: a review.
(3) Hoppe (1996) Pharmacoeconomics: https://www.ncbi.nlm.nih.gov/pubmed/10164058
(4) Boateng (2017) J Pharm Sci: https://www.ncbi.nlm.nih.gov/pubmed/28734784