Moderna and Excision BioTherapeutics are stepping into a battle with HIV, a 41-year epidemic that has confuddled drug developers and vaccine makers the world over.
The COVID-19 vaccine maker has started applying its mRNA technology to deliver a jab for HIV on the same day Excision says it's begun investigating a CRISPR-based therapy for the immune-system attacking virus.
The companies are attempting to upend the landscape for fighting HIV, as currently approved treatments, known as antiretroviral therapies, reduce the viral load to levels that can't spread to others, but the meds must be taken daily for life and the virus lives on hidden in the genome of T cells.
Moderna and Excision are launching into a drug development landscape that has tripped up major pharmaceutical companies. Last month, Merck was hit with 13 clinical holds for a slate of trials for an HIV therapy. The six full holds and seven partial ones cover the entire clinical development program for Merck's islatravir, which is being tested as a pre-exposure prophylaxis, an HIV-1 treatment and for other preventative measures.
For its part, Moderna is helping nonprofit scientific research group IAVI deliver HIV vaccine antigens using the COVID-19 vaccine maker's messenger RNA technology. The phase 1 trial, dubbed IAVI G002, is testing whether delivering priming and boosting HIV immunogens can spark certain B-cell responses and lead them to mature into broadly neutralizing antibodies. IAVI and Scripps Research created the immunogens, and the Bill & Melinda Gates Foundation is fronting the bill for the trial.
Trial sites in D.C., Atlanta, Seattle and San Antonio will enroll a total of 56 HIV-negative adults. Forty-eight of them will receive one or two doses of the vaccine and 32 of those will receive a booster vaccine, too. The remaining eight participants will get just the boost immunogen. Participants will be monitored for six months after the final vaccination.
Cambridge, Massachusetts-based Moderna and its partners said the use of mRNA could shrink vaccine development timelines by "years." If the pandemic we live in today is any sign, Moderna has proven as much. But HIV has been another story, as the epidemic just entered its fifth decade.
Meanwhile, Excision BioTherapeutics has boldly claimed its CRISPR gene editing-based therapy could be a "one-time curative treatment option" for the confounding infectious disease. The therapy, labeled EBT-101, did clear HIV from mice, but animal studies are difficult to translate in human testing.
The phase 1/2 trial will assess the safety and tolerability of one dose of the in vivo therapy in approximately nine patients who are on antiretroviral therapy for the virus and whose HIV viral load is undetectable. The patients will enter a long-term follow-up study after the initial 48-week one, which is taking place at sites in San Francisco, Orlando, St. Louis and Camden, New Jersey.
The therapy uses CRISPR-Cas9, which is a large enzyme that sometimes proves difficult to deliver because of its size. Excision's therapy is delivered intravenously using an adeno-associated virus, a transporting vector that has drummed up some concerns at the FDA.
Moderna and Excision's announcements come a day after researchers said Merck's blockbuster cancer med Keytruda helped bring dormant HIV out of hiding in patients living with both the virus and cancer who are on antiretroviral therapy, potentially changing the need for a daily pill regimen.