VANCOUVER, Wash.—According to the U.S. Centers for Disease Control and Prevention (CDC), some 1.14 million people aged 13 years and older are living with human immunodeficiency virus (HIV) infection. There are about 50,000 new HIV infections per year. Because HIV is such a big problem, the U.S. Food and Drug Administration (FDA) has given fast-track status to PRO 140, a drug candidate from CytoDyn Inc.
PRO 140 belongs to a new class of HIV/AIDS therapeutics—viral-entry inhibitors—that are intended to protect healthy cells from viral infection. PRO 140 is a humanized monoclonal antibody directed against CCR5, a molecular portal that HIV uses to enter cells. PRO 140 blocks the HIV co-receptor CCR5, and clinical trial results thus far indicate that it does not affect the normal function of the cell.
CytoDyn, a biotechnology company focused on developing subcutaneously delivered humanized cell-specific monoclonal antibodies as entry inhibitors for the treatment and prevention of HIV, recently announced the continuation of strong positive results for four weeks of monotherapy with PRO 140. Patients with HIV-1 are currently participating in the company’s Phase 2b treatment substitution trial. The company has requested an “end of Phase 2b meeting” with the FDA to discuss Phase 3 plans.
The Phase 2b clinical study was designed to investigate the potential of allowing patients to enjoy treatment interruption from their current HAART regimen concurrent with a monotherapy consisting of weekly injections of PRO 140. The results from the treatment substitution trial to date have demonstrated 100-percent success in suppressing the viral load among patients who had weekly injections of PRO 140 for four weeks of monotherapy. There were zero virologic failures among 21 patients who have reached four weeks of monotherapy, and 36 patients out of 40 have received at least the first injection of PRO 140. Now CytoDyn is requesting FDA clearance to conduct a larger, similar Phase 3 licensing trial to demonstrate further the efficacy of PRO 140.
As Dr. Nader Pourhassan, president and CEO of CytoDyn, explained, “Currently, there is no approved antibody therapy. We have the antibody … HIV patients will be able to stop taking pills and have a better quality of life while letting the body come back to itself. We believe we can suppress the infection for three months with the injections alone with low toxicity, low side effects and high patient acceptance.”
Comparing these results with previous studies used as historical controls supports the current study’s successful outcome. In a 37-patient trial of treatment interruption from highly active antiretroviral therapy (HAART), the use of multiple antiretroviral drugs in an attempt to control HIV infection, approximately 50 percent of patients experienced viral load breakout before four weeks, and approximately 100 percent showed viral load breakout at eight weeks. In another similar study, results indicated that 10 of 12 patients experienced viral load breakout after just two weeks of treatment interruption from HAART.
According to Pourhassan, “We believe this is a very strong indication that PRO 140 is effective to allow four weeks of drug holiday with weekly injections. PRO 140’s safety has been well documented in previous studies, as well as our current study.”
PRO 140 has been the subject of four Phase 1/1b and two Phase 2a clinical trials, each of which demonstrated its ability to significantly reduce HIV viral load in human test subjects. The PRO 140 antibody appears to be a powerful antiviral agent, leading to potentially fewer side effects and less frequent dosing requirements as compared to daily drug therapies currently in use.
Pourhassan described the commercial potential of PRO 140 as “huge.” CytoDyn acquired it from Progenix in 2012. Progenix, which worked on PRO 140 for more than a decade, chose to focus its efforts on cancer drugs. CytoDyn has received about $20 million for clinical trials with the drug in the past and recently received $8.4 million from the U.S. National Institutes of Health for a testing program at Drexel University.
“We believe this drug could change the paradigm of HIV treatment,” Pourhassan said. “The patient gets a holiday from taking pills, and the drug answers an unmet need by suppressing the patient’s viral load.”