–Study results show novel drug delivery system achieves long-lasting levels of three highly-potent antiretrovirals in the circulation in an animal model–
–Company developing long-acting oral formulations of HIV therapies to address viral resistance and improve therapeutic success–
Lyndra Inc., an emerging biopharmaceutical company developing oral dosage forms designed to release drug for up to a week or longer, today announced the publication of a feasibility study of an oral, once-weekly drug delivery platform for HIV antiretroviral therapy in the peer-reviewed journal Nature Communications. The study demonstrated proof-of-concept of sustained oral delivery of three key potent anti-HIV therapies – dolutegravir, rilpivirine and cabotegravir — in an animal model using a novel drug delivery system comprised of drug-polymer matrices. Based on these findings, Lyndra has begun initial development of an ultra-long-acting, sustained release oral dosage form that could be taken weekly.
The treatment of HIV was revolutionized by the creation of a single, once-daily combination pill. Yet, non-adherence to antiretroviral therapy occurs at a rate of about 30 percent, leading to treatment failure and driving the development of viral resistance. Long-acting injectable formulations of HIV medications that could release the drug for months and ease the burden of daily adherence are in clinical development and one from ViiV/Janssen is nearing approval, but their long-term favorability among patients and effect on adherence is unknown. Lyndra’s goal is to address the issue of nonadherence by using its platform, which has the potential to enable linear drug release of small molecules and peptides for seven days or more from each orally administered capsule, to develop long-acting HIV medications that can be administered orally.
“Because people with HIV require life-long antiretroviral therapy, a long-acting oral option that could be taken at home would make it easier for patients to adhere to their treatment regimen. By fitting into a patient’s regular routine, an ultra-long-acting therapy would be taken consistently, improving therapeutic success and helping avoid viral resistance,” said Andrew Bellinger, co-founder and chief scientific officer of Lyndra. “The findings of the feasibility study show the versatility of a variety of polymer matrices to formulate and deliver controlled release of three highly-potent antiretrovirals for a week after a single dose. Based on these findings, we are developing long-acting oral formulations of HIV therapies that can be commercialized. We believe these therapies could dramatically improve the probability of treatment success for patients who often forget to take their medicine on time.”
In the feasibility study, researchers used mathematical models to simulate HIV viral dynamics in the body under various levels of patient adherence to therapy. They then evaluated a week-long oral dosage form composed of distinct drug-polymer matrices and three antiretrovirals, dolutegravir, rilpivirine and cabotegravir. These drugs were selected because of mounting evidence supporting their efficacy either alone or in combination for maintenance therapy (i.e., in maintaining viral suppression). In the simulations, the polymer matrices achieved systemic drug levels of all three antiretrovirals for up to seven days after a single administration in an animal model.
Additionally, the researchers used mathematical modeling to evaluate the potential clinical and public health impact of long-acting oral antiretrovirals. They found that long-acting therapies would significantly reduce therapeutic failures and, if used prophylactically, could avert hundreds of thousands of new HIV cases.
“We are very encouraged with the results of this study examining the long-lasting levels of three highly-potent antiretrovirals in a well-established model,” said the co-author Robert Langer, a professor at the Massachusetts Institute of Technology and Co-founder of Lyndra. “Our ambition is to provide the HIV community with a new delivery system for antiretroviral therapy that would allow patients to take medication weekly instead of daily, with the expectation of significantly improving adherence and overall outcomes.”
Lyndra’s efforts to develop a weekly oral formulation of an HIV therapy with an optimized pharmacokinetic profile is supported in part by a five-year grant from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). The grant, awarded in May 2017, provides more than $3.6 million over five years to fund the formulation and preclinical development of a once-weekly oral HIV therapy to help increase patient adherence to antiretroviral treatment and pre-exposure prophylaxis (PREP; a strategy in which high-risk uninfected individuals take antiretrovirals to prevent HIV infection).
About Lyndra’s Platform
Lyndra’s orally administered dosage form is designed to deliver sustained, steady-state drug release for up to a week or longer by temporarily residing in the gastric cavity (stomach). Lyndra’s dosage form can deliver a wide range of active pharmaceutical ingredients. Once inside the gastric cavity, the dosage form, which is encapsulated in a familiar capsule, adopts a star-shaped configuration. It remains in the gastric cavity until pre-determined break points permit the formulation to split into small pieces and safely pass through the GI tract similar to indigestible food.
Providing a single, once weekly long-acting pill would eliminate the need for patients to take pills daily, thereby simplifying their lives and ensuring their disease is consistently and continuously treated. Less frequent dosing could reduce patient and caregiver burden, and improve patient compliance and health outcomes.
In addition to the work Lyndra is conducting with NIAID, the company is also developing a pipeline of ultra-long-acting therapies internally and with partners.
Lyndra aims to fundamentally change the way patients take medicines through the development of oral, ultra-long-acting, sustained release oral therapies that drastically improve healthcare outcomes. The Lyndra platform is based on technology licensed from the Massachusetts Institute of Technology, originally developed in the laboratory of Dr. Robert Langer funded by the Bill and Melinda Gates Foundation. Lyndra formulations transform medications taken daily or more frequently into a weekly or monthly dose, promising to improve patient adherence as well as optimize the pharmacokinetic profile of the dosage form. For more information, visit www.lyndra.com and follow the company on Twitter @LyndraInc.