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ASM - Primary Efficacy Results of PRO 140 SC in a Pivotal Phase 2b/3 Study in Heavily Treatment-Experienced HIV-1 Patients
  Single Shot of PRO 140 mAb Cuts HIV Load in Two Thirds on Failing ART
ASM Microbe 2018, June 7-11, 2018, Atlanta
Mark Mascolini
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 [1]. An extension study is testing longer-term response to PRO 140 in people using it with other antiretrovirals.
A humanized IgG4 mAb being developed by CytoDyn, PRO 140 inhibits HIV replication by blocking viral entry into CD4 cells that use the CCR5 coreceptor [2]. In a previously reported trial, 9 of 9 participants who took PRO 140 monotherapy for a week then added an optimized background regimen attained an undetectable viral load at week 25 despite initial resistance to multiple antiretrovirals [3]. 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 1 week before a switch to an optimized background regimen for 24 weeks [1]. 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 1-week double-blind period.
Participants had to have CCR5-using HIV, a viral load at or above 400 copies at screening for the trial, and documented resistance to at least 1 drug in 3 antiretroviral classes or to drugs in at least 2 classes and with limited treatment options. The trial excluded people with no viable treatment options except PRO 140. Investigators randomized 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 randomized to PRO 140, 14 (56%) completed the treatment phase of the study; among 27 people randomized 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 stood at 53.5 years. Participants had taken an average 11 antiretrovirals, and their HIV had documented resistance to an average 9.2 drugs. Median and average viral loads stood at 2814 and 21,104 copies, and median and average CD4 counts at 247.5 and 298.
Two thirds of trial participants randomized to PRO 140 versus one quarter randomized to placebo had at least a 0.5-log viral load drop after 1 week, a significant difference (64% versus 23%, P = 0.0032). Through week 25 CD4 counts rose by an average 84.3 cells and by a 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 $118,000 [4].
1. Dhody K, Kazempour K, Pourhassan N, Maddon PJ. 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.
2. AIDSinfo.gov. Drugs. PRO-140. https://aidsinfo.nih.gov/drugs/423/pro-140/0/patient
3. Dhody K, Maddon PJ, Kazempour 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.
4. i-base. FDA approves ibalizumab in the US to treat multidrug HIV resistance. March 2018.
ASM/2017 - PRO 140 CCR5 Monoclonal Antibody Strong in Highly Pretreated People: Week 25 - (ICAAC 2017 June 1) - (06/07/17)
CROI/2017: PRO 140 Single-Agent Maintenance Therapy for HIV-1 Infection: A 2-Year Update - (03/01/17)
CytoDyn Reports Primary Endpoint Achieved in PRO 140 Pivotal Combination Therapy Trial in HIV Infection - New HIV Drugs in development (02/23/18)
PRO140 SC Monotherapy (MT) Provides Long-Term, Full Virologic Suppression in HIV Patients - (06/22/16)
New HIV Drugs, Aging, Life Expectancy

ASM June 9 2018
Primary Efficacy Results of PRO 140 SC in a Pivotal Phase 2b/3 Study in Heavily Treatment-Experienced HIV-1 Patients
Kush Dhody1, Kazem Kazempour1, Nader Pourhassan2 and Paul J. Maddon3 1Amarex Clinical Research, LLC, Germantown, MD 2CytoDyn Inc., Vancouver, WA, 3Maddon Advisors LLC, Scarsdale, NY
Key Exclusion Criteria: CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus









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