HIV has been categorized as “the most intelligent virus in centuries.” This is due to the virus’ capability to hide in a reservoir inside organs and, also, because it mutates at a very high rate due inside CD4 cells. Essentially, the virus converts its RNA to DNA and makes sloppy copies of itself; and each copy is different from the origin and represents a resistance strain.However, now there’s a new hope for those suffering from HIV infection: the first self-injectable antibody, PRO 140, developed by CytoDyn Inc., has documented a 98% success rate in a Phase 2b clinical trial for patients with HIV. In a monotherapy study, some HIV patients using PRO 140 are experiencing a completely suppressed viral load for about 11 months, according to the company. And PRO 140 could be commercialized in 2017 if it receives positive results from an upcoming Phase 3 trial.
Current HIV treatment and the positives of PRO 140
Currently there are over 1.2 million individuals infected with HIV in the U.S., and about 56,000 new infections are reported each year. Worldwide, 33.4 million individuals are infected with HIV, with 2.7 million new infections annually reported. With the growing number of infections, about $15 billion is spent on therapy for HIV annually, in hopes to stop the spread of the virus.
Highly Active Anti-Retroviral Therapy, better known as HAART, is the current standard of care for HIV. HAART is a three drug regiment from two different classes and is taken daily for life. Since the introduction of HAART in 1996 by Dr. David Ho, HIV is no longer a death sentence; and there are about 30 approved drugs in five different classes included in the HAART regimen.
Yet, HAART poses problems, such as drug resistance, long-term morbidities, incomplete recovery of immune function, lifelong adherence and drug interactions. And this is one reason PRO 140 could revolutionize HIV therapy, it doesn’t have these issues, according to Dr. Nader Pourhassan, President/CEO, CytoDyn Inc.
“(Antibody research is important to vaccine and drug development for HIV) because we have no injectable products that can replace everyday pills,” says Dr. Pourhassan, President/CEO, CytoDyn Inc. in an interview with R&D Magazine. “(With PRO 140) an injection can be taken every week or month. And if a once-a-month injection works, then maybe this could be a functional cure and the next step to a vaccine, which has been long sought for the virus.”
PRO 140, a fully humanized monoclonal antibody, blocks the HIV co-receptor CCR5 on T-cells, preventing viral entry. “If HIV can’t enter the human cell, it will go away as the half-life of the virus is 24 hrs,” says Dr. Pourhassan.
However, PRO 140 is only effective against R5-exclusive virus, according to Dr. Pourhassan. This virus is present in 85% of early-stage HIV patients and 50% of late-stage HIV patients.
PRO 140 studies
In studies, PRO 140 effectively reduces viral loads by as much as 1.8log with one dose per week, according to the company. If the HIV patient’s viral load is completely suppressed, the transmission rate becomes almost zero.
The antibody is currently the only self-injectable antibody for HIV in Phase 3 trials. “The other injectable antibody being developed is via IV, and they are also in Phase 3 trials,” says Dr. Pourhassen. “Perhaps, maybe, a combination of these two injectable antibodies would be spectacular as a functional cure.” And they may also be most cost-effective than current antiretroviral therapies on the market.
However, for now, the path to first approval for PRO 140 is in the treatment experience population.
“Our Phase 3 protocol provides for an upcoming 25-week study with 300 HIV-positive patients,” says Dr. Pourhassan. “Selection of clinical sites, IRB approvals, patient screening and other administrative matters are underway and expected to be completed in time for the first patient to be dosed in the third quarter of this year. Although CytoDyn has a green light to start its Phase 3 clinical trial of PRO 140, the company may apply for a ‘breakthrough’ designation with PRO 140 as the first self-injectable antibody for HIV therapy.”
Phase 3 trials are expected to be conducted at over 30 sites in the U.S., and the company plans to submit its NDA for final approval of PRO 140 in November 2016.