Single dose PRO140 mAb reduces viral load by 0.5 log copies/mL in people with multidrug resistance
29 June 2018. Related: Antiretrovirals.
PRO 140, a once-weekly subcutaneous monoclonal antibody (mAb), lowered viral loads by a half-log or more in two thirds of phase 2b/3 trial participants after an initial injection in combination with a failing antiretroviral regimen. 
An extension study is testing longer-term response to PRO 140 in people using it with other antiretrovirals.
A humanised IgG4 mAb being developed by CytoDyn, PRO 140 inhibits HIV replication by blocking viral entry into CD4 cells that use the CCR5 coreceptor. 
In a previously reported trial, 9 of 9 participants who took PRO 140 monotherapy for a week then added an optimised background regimen attained an undetectable viral load at week 25 despite initial resistance to multiple antiretrovirals. 
In cell studies PRO 140 inhibited virus resistant to many antiretrovirals including the CCR5 antagonist maraviroc.
The new double-blind placebo-controlled study aimed to assess the efficacy, safety, and tolerability of PRO 140 added to a failing regimen for one week before a switch to an optimised background regimen for 24 weeks .
Researchers set the primary efficacy endpoint as a 0.5 log10 (about 3-fold) or greater drop in viral load at the end of the one-week double-blind period.
Participants had to have CCR5-using HIV, a viral load at or above 400 copies/mL at screening for the trial, and documented resistance to at least one drug in three antiretroviral classes or to drugs in at least two classes and with limited treatment options. The trial excluded people with no viable treatment options except PRO 140. Investigators randomised participants 1-to-1 in a double-blind fashion to PRO 140 or placebo plus the ongoing failing regimen for 1 week. Among 25 people randomised to PRO 140, 14 (56%) completed the treatment phase of the study; among 27 people randomised to placebo, 14 (52%) completed the treatment phase.
Of 52 trial participants, 38 (73%) were men, 27 (52%) were white, 24 (46%) were black, and 1 was Asian. Median age was 53.5 years. Participants had taken an average 11 antiretrovirals, and their HIV had documented resistance to an average 9 drugs. At baseline, median and mean viral load were 2814 and 21,104 copies/mL respectively, with median and mean CD4 counts at 247 and 298 cells/mm3.
Two thirds of trial participants randomised to PRO 140 versus one quarter randomised to placebo had at least a 0.5 log viral load drop after one week, a significant difference (64% versus 23%, p=0.0032). Through week 25, CD4 counts rose by a mean 84 cells/mm3 (median 64 cells). The researchers detected no anti-PRO 140 antibodies during the study.
No one stopped study drugs because of adverse events and no toxicity pattern emerged. Seven of 52 participants (13.5%) had 1 or more treatment-related adverse events. Injection site reactions affected fewer than 10% of participants; all such reactions were mild and all resolved.
At the time of this presentation, 35 people enrolled in an extension study that prolongs access to PRO 140 when the treating physician believes the mAb is essential to building a suppressive regimen.
People should be able to self-inject PRO 140 subcutaneously once weekly. The FDA designated PRO 140 a Fast Track drug candidate. Ibalizumab, a licensed mAb, blocks HIV entry to CD4 cells by binding to the CD4 receptor. The annual wholesale cost of ibalizumab is US $118,000. 
The study is registered at clinicaltrials.gov.  The slides from the conference presentation are also helpfully posted after this original article on NATAP.org.
It is unclear why the loss to follow-up rate was so high in this study. Although 0.5 log is relatively modest, this can be sufficient to support a new combination in people who have other active drugs. Previous studies with PRO 140 have reported greater antiviral activity with continued dosing.
A second phase 2b/3 study – not recruiting – is looking at maintenance therapy with PRO 140 monotherapy (without other ART) as a switch option in 300 people who have sustained undetectable viral load on their current ART. 
PRO 140 is given as a 350 mg weekly sub-cutaneous injection that can be self-administered at home.
Mascolini M. Single shot of PRO 140 mAb cuts HIV load in two thirds on failing ART. (11 June 2018). (With slides).
- Dhody K et al. Primary efficacy results of PRO 140 SC in a pivotal phase 2b/3 study. ASM Microbe 2018, June 7-11, 2018, Atlanta. Abstract AAR LB15.
- AIDSinfo.gov. Drugs. PRO-140.
- https://aidsinfo.nih.gov/drugs/423/pro-140/0/patientDhody K et al. Interim results of PRO 140 in a phase 2b/3 study in treatment-experienced HIV-1 patients with multiple ARV class resistance. ASM 2017/ICAAC, June 1-5, 2017, New Orleans.
- HIV i-Base. FDA approves ibalizumab in the US to treat multidrug HIV resistance. HTB March 2018.
- https://i-base.info/htb/33659Clinicaltrials.gov. A randomized, double-blind, placebo-controlled trial, followed by single-arm treatment of PRO 140 in combination w/ optimized background therapy in treatment-experienced HIV subjects (PRO 140).
- https://www.clinicaltrials.gov/ct2/show/NCT02483078Clinicaltrials.gov. Study of PRO 140 SC as Single agent maintenance therapy in virally suppressed subjects with CCR5-tropic HIV-1 infection.