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ICAAC 2007: Chicago, Illinois; September 17-20, 2007

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The Body Covers: The 47th Interscience Conference on Antimicrobial Agents and Chemotherapy
ICAAC 2007 Highlights: An Interview With Cal Cohen, M.D., M.S.

September 20, 2007

Cal Cohen, M.D.
Listen (1.9MB MP3, 5 min.)

This is Bonnie Goldman, Editorial Director of The Body PRO. I'm here in Chicago at ICAAC 2007 with Dr. Cal Cohen, Research Director of the Community Research Initiative of New England and Clinical Instructor at Harvard Medical School in Boston.

ICAAC 2007 featured a lot of presentations on antiretrovirals in development. In a separate interview, Dr. Cohen covered drugs in later development, and here Dr. Cohen is going to give us an overview of research presented on HIV drugs in preclinical development.

In this conference, Gilead presented some in vitro data about a nucleoside inhibitor that they are working on.1-3 A nucleoside called 9148 [full drug name: GS-9148] that they are working on in some in vitro studies. It has some interesting properties, including maintaining activity despite a lot of the common resistance mutations that we see in the field right now.

Antiretrovirals in Advanced Development
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Antiretrovirals in Early Development
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We've got not just etravirine [also known as TMC125],4 but a couple of other non-nucleosides [NNRTIs] that were presented at this meeting. We've got a drug from the Pfizer group called UK-453 [full drug name: UK-453,061]5 that -- at the Sydney conference [the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2007)]6 and once again here -- had some data to support that it has the potential for great activity. It also looked like a once-a-day drug based on the Sydney data.

Another company, called Ardea, has a drug that they're bringing forward called RDEA806,7 which looked like a pretty good drug and certainly maintained activity at least in vitro, despite non-nucleoside resistance.

We even have some new integrase inhibitors: one that GSK [GlaxoSmithKline] is bringing forward8 and some other preclinical integrase inhibitors that were identified, and then finally some other R5 inhibitors.

A company called Progenics is bringing along an infusion R5 inhibitor called PRO 140.9 We saw some data at this conference to support that a single dose of this drug had some pretty potent activity -- nearly about a 2-log viral load drop -- and [that this drug] would require infusions certainly infrequently, perhaps maybe every once or two weeks. We shall see.

There's another small molecule oral R5 inhibitor that was presented in Sydney, being studied by a group called Incyte. That molecule, called 9471 [full drug name: INCB9471], has as its interesting advantage a very long half-life, about a 60-hour half-life.10 It also can be ritonavir [brand name: Norvir; also known as RTV]-boosted, and so that compound also looks very interesting, with a good nadir, about a 1.8-log nadir.11

Two-Year Follow-Up of Treatment-Experienced Pations on Vicriviroc (VCV)
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Finally, we've got vicriviroc [also known as: SCH 417690, SCH-D], being studied by Schering.12 They updated us on their experience with vicriviroc. The important news in this conference was that the data are now out to over two years. Indeed, some patients have been on vicriviroc for three years. With all the questions about the new class, this study helps to address them, although there are only 39 patients being studied at this period of time.

Nevertheless, the news continues to be good. Sixty percent of this cohort of 39 people have viral loads less than 50. The few people who have had virologic rebound have rebounded with a dual-tropic virus, but certainly nothing unexpected there.

Of the 12 discontinuations, half were by choice and only two were attributed to adverse events. Also, the group at Schering reassured us that, so far, in the past roughly year and a half of follow-up, there's been very little in terms of concerns for: oncological issues, seizures, cardiovascular events; indeed, very low rates of illnesses overall in this cohort of 39 people.

So, we're getting reassuring news of some of the drugs that are in phase 2/3, and some good news that there continues to be a pipeline behind these drugs.


Footnotes

  1. Laflamme G, Grant D, White K, et al. Novel nucleotide inhibitor GS-9148 selects for a K70E mutation in HIV-1 reverse transcriptase (RT) and low-level resistance in vitro. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1037.
    View poster: Download PDF
  2. Laflamme G, Grant D, Boojamra C, et al. Novel 2'-fluoro substituted nucleotide HIV reverse transcriptase inhibitor GS-9148 exhibits low potential for mitochondrial toxicity in vitro. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1038.
    View poster: Download PDF
  3. White KL, Ly JK, Eastoak-Siletz A, et al. Resistance mechanisms of the K70E HIV-1 reverse transcriptase mutant to GS-9148 and other NRTIs. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1039.
    View poster: Download PDF
  4. Cahn P, Haubrich R, Leider J, et al. Pooled 24-week results of DUET-1 and -2: TMC125 (etravirine; ETR) vs placebo in 1203 treatment-experienced HIV-1-infected patients. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-717.
    View slides: Download PowerPoint
  5. Corbau R, Allan G, Burt C, et al. UK-453,061: a non-nucleoside reverse transcriptase inhibitor for the treatment of drug-resistant HIV infections. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract F1-945.
    View poster: Download PDF
  6. Fätkenheuer G, Staszewski S, Plettenburg A, et al. Short-term monotherapy with UK-453,061, a novel NNRTI, reduces viral load in HIV infected patients. In: Program and abstracts of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Abstract WESS202.
  7. Girardet J, Koh Y, De La Rosa M, et al. The discovery of RDEA806: a potent new HIV NNRTI in phase I clinical trials. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1040.
  8. Golden PL, Piscitelli S, Min S, et al. In vitro antiviral potency and preclinical pharmacokinetics of GSK364735 predict clinical efficacy in a phase 2a study. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1047.
    View poster: Download PDF
  9. Ketas TJ, Maddon PJ, Olson WC. Comparative susceptibility of HIV-1 and HIV-2 to the humanized CCR5 monoclonal antibody PRO 140. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1029.
  10. Shin N, Solomon K, Wang KH, et al. INCB9471 is a non-competitive small molecule antagonist of CCR5. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1032.
  11. Solomon K, Baribaud F, Shin N, et al. INCB9471 is a potent inhibitor of R5-HIV-1 infection in vitro. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1033.
  12. Gulick R, Haas D, Collier AC, Lennox J, Parker C, Greaves W. Two-year follow-up of treatment-experienced patients on vicriviroc (VCV). In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1030.



  
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