Beating the Opioid Crisis: Human Trials for Fentanyl and Heroin Vaccines Nearing Launch

Developing Solutions to Combat the Opioid Crisis: Advancing Towards Human Trials for Fentanyl and Heroin Vaccines

In a significant stride towards addressing the opioid crisis, researchers are in the process of developing vaccines that hold the potential to prevent overdoses caused by heroin and fentanyl. Human trials for these groundbreaking vaccines are anticipated to commence in the early months of 2024. The comprehensive research initiative, generously funded by the National Institutes of Health (NIH), is a collaborative effort involving multiple institutions, all united in the objective of nullifying the effects of these harmful opioids without disrupting ongoing treatments for opioid addiction.

Collaborators, primarily scientists from the University of Montana in conjunction with their partners, are on the cusp of launching human trials for vaccines engineered to counteract the perilous consequences of fentanyl and heroin overdoses.

The purpose of these vaccines is to serve as a protective barrier for individuals grappling with substance addiction, as well as those who are particularly susceptible to accidental overdoses. Disturbing statistics from the National Institutes of Health underscore the urgency of this endeavor, revealing that in the year 2021 alone, the United States witnessed more than 106,000 fatalities stemming from drug overdoses. Shockingly, approximately 71,000 of these tragic deaths were attributed to synthetic opioids like fentanyl.

Leading this pioneering effort is Dr. Jay Evans, who directs the UM Center for Translational Medicine, an institute deeply involved in the vaccine development. Dr. Evans is also a co-founder of Inimmune, a corporate collaborator tasked with scaling up the production of vaccine components. The company operates within MonTEC, the University of Montana’s Missoula-based business incubator.

Dr. Evans outlined the timeline for this venture, stating, “We are poised to commence human trials for our vaccines in early 2024. The initial focus will be on a heroin vaccine, followed shortly by a fentanyl vaccine, both of which will undergo Phase I clinical trials. Once we establish the safety and early efficacy of these vaccines in the first round of clinical trials, we aspire to progress to a combined multivalent vaccine that targets both heroin and fentanyl.”

This ambitious endeavor traces its origins back to the work of Dr. Marco Pravetoni, a distinguished professor in the field of psychiatry and behavioral sciences at the University of Washington. Dr. Pravetoni, who directs the Center for Medication Development for Substance Use Disorders, leads a research team that specializes in creating haptens and drug conjugate vaccines capable of stimulating the production of antibodies against the target opioids.

Dr. Pravetoni has dedicated over a decade to researching vaccines against opioids, a commitment that led to the advancement of an oxycodone vaccine to Phase I clinical trials. This progress was made possible through collaboration with Dr. Sandra Comer from Columbia University.

A cornerstone of the vaccine development is the addition of the UM team’s patented adjuvant named INI-4001 to the vaccine formulations. Adjuvants, compounds known for enhancing vaccine efficacy, play a crucial role in bolstering the immune response.

Dr. Evans elucidated, “Our adjuvants significantly enhance the immune response generated by the vaccines, leading to a more robust and enduring immunity. Over the past few years, we’ve worked closely with researchers from institutions such as Inimmune, the University of Minnesota, the University of Washington, Hennepin Healthcare Research Institute, and Columbia University to meticulously design and optimize anti-opioid vaccines for progression to human clinical trials.”

The financial support for this endeavor is entirely provided by the National Institutes of Health. Several years back, the University of Montana secured a substantial $33.4 million contract to spearhead the development and advancement of two candidate anti-opioid vaccines through Phase I clinical trials. This critical work aligns with the NIH’s Helping to End Addiction Long-Term (HEAL) initiative.

Before embarking on human trials, the vaccines underwent rigorous testing using animal models. Mice were tested at the University of Montana, while rats and pigs were utilized in experiments conducted at the University of Minnesota. Recently published papers in the NPJ Vaccines journal highlighted the positive impact of the TLR7/8 adjuvant on the effectiveness of the fentanyl vaccine among animals. Publications focusing on the success of the heroin vaccine are anticipated in the near future.

The intricate process of vaccine development involves various stages, with the heroin vaccine expected to enter Phase 1 human trials ahead of the fentanyl vaccine, despite the fentanyl-related papers being published first. The team is gearing up to finalize their Investigational New Drug applications to be submitted to the FDA later this year.

Dr. Comer at Columbia University in New York City will oversee the Phase 1 human trials. The process of recruiting and enrolling participants, specifically individuals who use fentanyl or heroin, is anticipated to span six months or more. Notably, DrugAbuse.com highlights a disheartening relapse rate of approximately 90% among heroin and opioid users. Dr. Evans believes that these vaccines hold the potential to save lives and provide valuable assistance to those seeking treatment.

The Phase 1 trials involve a careful approach to dose escalation. Dr. Evans elaborated, “We initiate the trials with the lowest dose, a dose that may not exhibit significant efficacy. The primary focus during Phase I clinical trials revolves around ensuring safety. Following the completion of the first dose cohort, a data safety monitoring board reviews the accumulated data and approves the testing of subsequent dose levels, provided the vaccine’s safety is confirmed. This methodical process continues until we attain dose levels that are both safe and efficacious.”

Subsequent phases of the trials encompass evaluating the number of doses required for effectiveness and determining optimal intervals between doses. Phase 3 marks a pivotal step, involving an efficacy study with a substantial participant pool. The FDA relies on data from this stage to assess whether the vaccine’s benefits outweigh potential risks.

Dr. Evans emphasized the meticulous nature of this journey, highlighting, “The path to obtaining final approval for a product is indeed lengthy, spanning multiple years. Drawing upon the efficacy data derived from preclinical studies and the well-established safety profile observed in animal models, we maintain a strong sense of optimism regarding the success of these vaccines. Nevertheless, there remains a significant amount of work ahead.”

Efforts are also underway to facilitate the process development and scale-up manufacturing of the vaccine products necessary for Phase 1 human trials. Inimmune and the University of Washington are at the forefront of these critical tasks, ensuring that the production adheres to “GMP” or good manufacturing practices.

Together, the UM Center for Translational Medicine and Inimmune employ around 70 individuals across their campuses. Their collaborative efforts form one of the largest university-based academic research teams dedicated to vaccine discovery and development in the United States. Notably, their contributions garnered recognition in the form of inclusion on a list titled “Best Universities Solving the Coronavirus Pandemic” in 2020.

In parallel with the efforts targeting anti-opioid vaccines, the UM team is actively involved in developing vaccines to counter other medical challenges. These include SARS-CoV-2, influenza virus, tuberculosis, monkeypox, pertussis, pseudomonas, Lyme disease, valley fever, malaria, E. coli infections, allergies, and even cancer.

Dr. Evans anticipates further progress in the coming years, asserting, “We expect to witness additional vaccine candidates advancing to Phase I clinical trials. This includes a mix of novel vaccines and improved versions of existing vaccines, all enriched with adjuvants to enhance safety, durability, and efficacy, especially in vulnerable populations.”

Dr. Evans also highlighted the invaluable contribution of UM students to this ambitious endeavor. Undergraduate interns, graduate students, and postdoctoral researchers actively contribute to the work conducted within their labs. Dr. Evans expressed his appreciation for the energy and enthusiasm that students infuse into their work, which serves to invigorate the entire research process. As he aptly summarized, “In addition to our core goal of innovating new treatments and medications, we are equally committed to the education of students.”

Frequently Asked Questions (FAQs) about Opioid Crisis Solutions

More about Opioid Crisis Solutions

• National Institutes of Health (NIH)
• UM Center for Translational Medicine
• University of Washington Center for Medication Development for Substance Use Disorders
• Inimmune
• DrugAbuse.com
• NPJ Vaccines journal
• Columbia University