Positive results support the continued development of PRO 140 – CytoDyn’s investigational humanised monoclonal antibody for the treatment of patients with HIV who are failing their current ART regimens. “While ART has greatly advanced over the years, new agents are needed to improve the potency and pharmacokinetic profiles, decrease toxicity, combat drug resistance and improve convenience to facilitate patient compliance,” Dr Nader Pourhassan, CytoDyn’s president and CEO, is quoted in a Healio report as saying.
The PRO 140 monoclonal antibody was developed to bind to the CCR5 receptor, blocking HIV from infecting target cells. Fifty patients infected exclusively with CCR5-tropic HIV-1 and who had documented resistance to at least two antiretroviral (ARV) drug classes participated in a recent two-part study. During the first week, the participants were randomly assigned to receive a single, 350-mg subcutaneous injection of PRO 140 or placebo. All patients continued on their failing ART regimen. In the second part of the study, all participants received 24 weeks of open-label PRO 140 with an optimized background regimen.
According to the researchers, the participants’ mean baseline viral load was 4.32 log10. On average, participants were treated with at least 10 previous ARVs and were resistant to at least nine.
One week following a single injection of PRO 140, patients achieved a mean viral load reduction of approximately 97% from baseline. According to the researchers, the trial met its primary efficacy endpoint – the proportion of patients with at least 0.5 log10 reductions in HIV-1 RNA from baseline at the end of the 1-week treatment period (P < .01).
The researchers said PRO 140 was generally well-tolerated, and there have been no drug-related serious adverse events or treatment discontinuations reported to date. So far, 32 patients have completed the study, 17 are ongoing and three discontinued the study early. The researchers are providing continued access to PRO 140 to patients who completed 25 weeks of therapy.
Weekly, 350-mg injections of PRO 140 have previously shown that the regimen could potentially be used as a standalone therapy for some heavily treatment-experienced patients. In a 12-week study, patients who were treated with PRO 140 maintained virologic suppression after discontinuing their ART regimen.
“With the highly favourable efficacy results for this combination therapy trial, and data from our previous trials and our ongoing monotherapy trial, we are now working toward the filing of a biological license application, or BLA, with the US Food and Drug Administration (FDA) for PRO 140 in the combination therapy indication,” Pourhassan said.
In March, the FDA approved ibalizumab – another long-acting humanised monoclonal antibody developed for the treatment of multidrug-resistant HIV in adults who are failing their current ART regiments.
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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 fully humanized IgG4 monoclonal antibody directed against CCR5, a molecular portal that HIV uses to enter T-cells. PRO 140 blocks the predominant HIV (R5) subtype entry into T-cells by masking this required co-receptor, CCR5. Importantly PRO 140 does not appear to interfere with the normal function of CCR5 in mediating immune responses.
Jay Lalezari, Kush Dhody, Ula Kowalczyk, Kazem Kazempour, Nader Pourhassan, and Paul J Maddon