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Author Topic: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?  (Read 5367 times)

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Offline mercuryman

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Good evening.....I'm one of those people who is resistant to most HIV drugs......

I will be starting a new "study drug" in the next month or so......Ibalizumab (TNX-355 or TMB-202); The only other active drug that I have to pair with Ibalizumab is Etravirine.....I will also be taling Prezista/Norvir/Truvada (to which I have little sensitivity)

I was wondering if someone could shed some light on their knowledge/experience with Ibalizumab? I guess I am most concerned about resistance issues......Your input is appreciated......

I have had difficulty getting firm answers from Clinical coordinators about how other patients have done on this drug.....

My current T cells are at 9; VL=600,000.......I need a regimen to sustain me for the foreseeable future.

Thank you.....

Offline Ann

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #1 on: February 03, 2010, 09:06:15 PM »
Hi Mercury, welcome to the forums.

Although I do not have personal experience with this drug, my hiv doc and I have discussed it. He's an hiv pharmacologist and he thinks this is going to be the next big salvage therapy that will save people such as yourself, much like Fuzeon did a few years ago. Have you read our info page on Ibalizumab?

I hope this works for you. Please keep us posted.

Hugs,
Ann
xxx

PS - are you also resistant to the new class - Integrase Inhibitors? There is a new drug in that class called elvitegravir / GS-9137 that my doc is very optimistic about.
« Last Edit: February 03, 2010, 09:13:28 PM by Ann »
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Offline mercuryman

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #2 on: February 03, 2010, 09:40:24 PM »
Ann,
Thanks for your response! Yes, given that I'm dual-tropic, Ibalizumab will be helpful in blocking the X4 & R5 receptors.......I will check out your info on Ibalizumab......

Where integrase inhibitors are concerned......I'm resistant to Ratelgravir (therefore, due to cross-resistance, Eltegravir would not be an option). There is a GSK Intergrase inhibitor that is in early phase 2 of clinical trials.......from my readings, it would NOT be cross-resistant with Ratelgravir and Eltegravir. So I would have to wait for another clinical trial to open up on down the line......

My best to you......

Rob (mercuryman)

Offline veritas

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #3 on: February 04, 2010, 06:33:37 AM »
Rob,

Sorry to hear about your "mutation" issues. I, too, am resistant to most older medications due to monotherapy back in the nineties. Do you know how you became resistant to Isentress ? I have been taking Isentress since it has been approved.

CAVD is studing Ibalizumab under Dr. David Ho ( he pioneered the use of PI's in treating HIV) see:

http://en.wikipedia.org/wiki/David_Ho_(scientist)

http://www.cavd.org/grantees/Pages/HoIDC.aspx

This mab has also been fast-tracked, so it seems to be pretty safe.

Please keep us informed on your results in the trial, since I believe there are many in your position (including me).

Your in good hands with Dr.Ho at the helm.

v
« Last Edit: February 04, 2010, 06:38:52 AM by veritas »

Offline Ann

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #4 on: February 04, 2010, 07:18:17 AM »
You're welcome, Rob.

That's a shame you're resistant to Isentress. I assume the other intergrase inhibitor you mention is GSK-572? There appears to be no studies currently recruiting. (hehehe.... my google spell-check just suggested intergalactic  in place of intergrase...)

However, there is at least one study currently recruiting for ibalizumab (as V mentioned). Have you also looked into the other up-and-coming Entry Inhibitors? For that matter, have you already tried Fuzeon and/or Selzentry/Celsentri?

Good luck, Rob. I've got my fingers and toes crossed that you find something soon.

Ann
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"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Offline John2038

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #5 on: February 04, 2010, 03:20:31 PM »
Hi Rob,

Welcome to this forum !

Among the possible approach, you may want to well consider the others clinical trials you may be part of prior taking part of Ibalizumab study. As such, I have try to summarize some of the new drugs currently in the pipeline.

You may want then to look for possible trials on them here: http://clinicaltrials.gov

I would suggest you contact those trials investigators and see with them how you might benefit from them.

Prior that, have consider etravirine + darunavir/r + raltegravir  as a possible treatment option with your ID Doc ?

Here is the well-known study if you don't know it already:
http://www.aidsmap.com/en/news/5AA6E0BE-D302-45A1-AB20-1F56B2B8825D.as
You may also add to it the Fuzeon.

Below, the non-exhaustive non ordered list of drugs under development.

I wishes you to find the right combo very soon !

John


Maturation inhibitors
 
Beviramat//MPC 4326 Myriad Pharmaceuticals
Predicting Bevirimat resistance of HIV-1 from genotype
http://www.biomedcentral.com/1471-2105/11/37
HIV Maturation Inhibitor Bevirimat Demonstrates Promising Safety and Efficacy in Patients with Responsive HIV Genotype
http://www.hivandhepatitis.com/2009icr/icaac/docs/092509_a.html


New nucleosides

Apricitabine, Avexa Limited
Apricitabine is a second-generation nucleoside reverse transcriptase inhibitor (NRTI) designed to work against virus that’s resistant to lamivudine (found in Epivir, Combivir, Epzicom and Trizivir).
http://www.aidsmeds.com/articles/hiv_apricitabine_atc_1667_16760.shtml

DAPD (amdoxovir) RFS Pharma
AMDX was effective in subjects with virus strains resistant to nucleoside reverse transcriptase
inhibitors (NRTI), including those harboring multiple thymidine analog mutations (TAMS) such
as the M41L and L210W mutations and also the M184V mutation selected by Epivir® and
Emtriva®. Trends towards better responses were associated with viruses with fewer than six
NRTI mutations (p = 0.12) and less than four TAMS without E44D or V118I (p = 0.08).
http://www.rfspharma.com/Assets/AMDX%20Data%20Press%20Release.pdf


Investigational nonnucleoside reverse transcriptase inhibitors

RDEA806 Ardea Biosciences
Pharmacokinetic results from a Phase 2a study of a new NNRTI from Ardea, previously shown at Mexico, was presented by Graeme Moyle from the Chelsea and Westminster Hospital, London. [1]
Two cohorts of 12 treatment-näive HIV-positive patients were randomised (9 active: 3 placebo) to receive either RDEA806 400 mg twice daily (BID), or 600 mg once daily (QD), for 7 days and a single morning dose on day 8 for PK monitoring. All patients achieved viral load reductions of 1.5 - 2.0 log with a trend between reductions and Ctrough (but not Cmax or AUC).
http://www.i-base.info/htb/v9/htb9-11-12/Studies.html


IDX899 and IDX989 GSK and idenix pharmaceuticals
Both are new non-nucleoside reverse-transcriptase inhibitors (NNRTIs) that exhibit potent inhibition of HIV-1 replication, including NNRTI-resistant mutants. This microdose study investigates the pharmacokinetics and determined oral bioavailability. For each compound, 4 healthy male subjects are randomized to receive via a crossover design a single 100-µg oral and intravenous dose together with 100 nCi of [14C]-labeled drug. Plasma and urine samples are obtained over a period of 168 hours postdose and analyzed for total, unchanged drug and major metabolites using an accelerator mass spectrometry method. Based on total radioactivity, oral absorption is near complete. For the parent drug, mean absolute bioavailability is 61% and 65% for IDX899 and IDX989, respectively. Both compounds are extensively metabolized especially after oral dosing. Observed terminal phase half-lives after oral and intravenous doses range from 4 to 10 hours and are comparable for the 2 compounds.
http://jcp.sagepub.com/cgi/content/abstract/49/12/1408

Integrase inhibitors

S/GSK1349572 Shionogi-GlaxoSmithKline pharmaceuticals
A next generation integrase inhibitor with activity against integrase inhibitor resistant clinical isolates from patients experiencing virologic failure while on raltegravir therapy
http://www.ias2009.org/pag/Abstracts.aspx?AID=2051


CCR5 inhibitors

PRO140 progenics pharmaceuticals
A monoclonal antibody to CCR5
http://www.progenics.com/prod_pro140.cfm


Other drugs and novel strategies

Gene therapies

VRX496 from VIRxSYS
http://www.eurekalert.org/pub_releases/2009-02/uops-pmp021009.php

See also
http://www.medicalnewstoday.com/articles/139117.php
http://www.webmd.com/hiv-aids/news/20090216/hiv-gene-therapy-major-advance

-----------

More

GS-9148 Nucleotide Active Against Resistance
The investigational nucleotide reverse transcriptase inhibitor (NRTI) GS-9148 (GS-9131 is prodrug) maintains potent activity against a majority of clinically observed resistance mutations.
http://www.natap.org/2009/ResisWksp/ResisWksp_12.htm

Elvucitabine (ACH-126,443, Fd4C) Achillion Pharmaceuticals
Elvucitabine’s efficacy in this study, in regard to intention-to-treat analysis, show that it is nonsignificantly inferior to 3TC. Earlier reports from 24 weeks study demonstrated more adverse side affects in the ELV arm which was not the case at 48 weeks. This drug will require further studies, for long-term antiviral activity and safety.
http://www.i-base.info/htb/v9/htb9-11-12/Studies.html


Racivir Pharmasset, Inc.
Have demonstrated antiviral activity in patients harboring HIV with the M184V mutation and less than three thymidine analog mutations. These patients have genotypes consistent with first-line therapy failure and may be candidates for second line treatment regimens that contain Racivir. Future studies will be designed to explore this potential use of Racivir in a combination therapy for second-line therapy.
http://www.pharmasset.com/pipeline/racivir.asp

Intelence
Intelence is approved for treatment-experienced patients who have HIV strains that are resistant to an NNRTI and other HIV drugs. It is not yet approved for people starting antiretroviral therapy for the first time.
http://dovepress.com/profile-of-etravirine-for-the-treatment-of-hiv-infection-peer-reviewed-article-TCRM

TMC278 (rilpivirine)
A Next-Generation Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI), Active against Wild-Type and NNRTI-Resistant HIV-1
http://aac.asm.org/cgi/content/abstract/54/2/718

Blockade of X4-Tropic HIV-1 Cellular Entry by GSK812397
A Potent Noncompetitive CXCR4 Receptor Antagonist
http://aac.asm.org/cgi/content/abstract/54/2/817

RDEA427 and RDEA640 Are Novel NNRTI with Potent Anti-HIV Activity against NNRTI-resistant Viruses
RDEA427 has shown potent in vitro activity against wild-type and NNRTI-resistant viruses.
Both experimental drugs worked better than Sustiva against a panel of NNRTI-resistant viruses.
http://retroconference.org/2009/PDFs/569.pdf
http://www.ardeabio.com/Docs/RDEA427%20and%20RDEA640%20are%20Novel%20NNRTIs%20with%20Potent%20Anti-HIV%20Activity.pdf

Anti-viral Characterization in vitro of a Novel Maturation Inhibitor, MPC-9055 Vivecon
Vivecon has been tested extensively for antiviral activity and safety with both in-vitro and in-vivo models, in preclinical studies. It demonstrated antiviral activity of less than 10 nanomolar IC50 against the HIV virus, with at least a 1,000-fold therapeutic safety index. Vivecon was also shown to be active against viral strains that are resistant to currently marketed anti-HIV drugs, including nucleoside reverse transcriptase inhibitors such as AZT [zidovudine; Retrovir], non-nucleoside reverse transcriptase inhibitors such as efavirenz [Sustiva], and protease inhibitors such as ritonavir [Norvir].
http://www.hivandhepatitis.com/recent/2008/092308_c.html

CHX157
A prodrug similar to tenofovir-DF
http://www.i-base.info/htb/v9/htb9-7-8/Pipeline.html

IDX899: an NNRTI in development with Idenix
IDX899 was shown to remain sensitive (<4 fold change from wild-type) to 20/23 single, double and triple site directed mutations, with greater resistance seen to Y181C (14 fold), E138K/Y181I (11 fold) and E138K/Y181I/M230L (900 fold). It also retained sensitivity to viral pools selected through exposure to efavirenz and etravirine (TMC-125), and retained greater sensitivity to each pool compared with efavirenz, etravirine of TMC-278 (rilpivirtine)
http://www.i-base.info/htb/v9/htb9-7-8/Pipeline.html

SPI-256 (Novel Pharmakocinetic ehancer) Sequoia Pharmaceuticals Inc.
“Sequoia Pharmaceuticals’ PKE development program has demonstrated significant progress toward fulfilling the unmet medical need for a safe and well tolerated PKE that potently enhances the pharmacokinetics of target compounds without the risk of promoting the emergence of resistant mutants due to its lack of antiviral activity.”
http://www.sequoiapharmaceuticals.com/news_press/news_press.html

OBP-601
The anti-HIV activity of the compound persists longer than other NRTIs in test tube study, including against the common NRTI-resistance mutation, M184V. OBP-601 seems to effectively suppress HIV in both wild type and multidrug resistant forms of the virus. The 100mg dose given once a day provided good suppression of virus for 24 hours and is currently under study to further assess its safety and effectiveness in HIV-positive people.
http://www.thebody.com/content/news/art51579.html


Further Reading
http://natap.org/2009/CROI/croi_55.htm
http://www.natap.org/2009/HIV/011110_02.htm

Offline mercuryman

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #6 on: February 04, 2010, 10:29:53 PM »
V,
How did I develop resistance to Isentress? I was involved in a study from Aug 06 - Mar 08. basically, i was on monotherapy, as my OBT was a failing regimen. My VL at got down to 11,000 at its lowest while on this study. My VL eventually increased with each blood draw. My ID Doc assumed that I had developed resistance to Isentress due to the unimpressive clinicals. I have NOT been involved with any other drugs from the Integrase class, as my doc does not want me to develop any further resistance. Eltegravir will be a NO GO, due to cross resistance with Isentress. I'm holding out hope that the GSK Integrase Inhibitor will be available in NEW studies by 2011......Time will tell, in the mean time, I must apply a "Bandaid of sorts", and go with the Ibalizumab/Etravirine (fully active) & Prezista/Norvir/Truvada (all to which I have very little sensitivity). I will keep everyone informed with my progress when I start this study. I'm also dual tropic.....which further limits my options for now.......Maybe when an X4 inhibitor arrives on the scene, I could couple that with a R5 drug. I had been on Selzentry for about 6 months (in an attempt to boost my T cells); unfortunately, that drug did nothing for me......so my ID Doc removed that drug from my regimen. I hope that you're currently on a stable regimen which works well for you.....

Ann,
Yes, I had been on T-20 years ago and eventually developed resistance. Selzentry does nothing for me without having an X4 inhibitor to add to the mix....maybe one day that will happen!

John,
Again, thanks for the WEALTH of information....I have researched some of these drugs and have spoken to a few clinical coordinators in the recent past. My biggest issue at times is qualifying for protocols...given that I have such low t cells and a healthy viral load.

I haven't been tested for sensitivity to Bevirimat.....I'm not putting all my eggs in one basket on that drug, as I have lots of PI resistance. Its my understanding that individuals with numerous PI mutations will probably not respond well to Bevirimat. Correct me if I'm wrong. I've also read about Vivecon in the past.....possibly more effective than Bevirimat? So far, I'm a Virgin to the Maturation Inhibitors...

I was hoping that the NRTI.....Apricitabine, would be available by now to add to the mix. However, looks like it may be 2011 at the earliest before I could access that drug....

I was NOT familiar with the GSK X4 entry inhibitor.....I didn't find any clinical trials for it?

Also, the GS-9148 NA, sounds like a good match for me.....didn't find any trials available for this one....

I'll keep plugging away in search of future studies; in the meantime, I value any information/advice that any of you have to offer, based on your experiences....

Have a good evening...

Rob

Offline John2038

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #7 on: February 05, 2010, 02:03:56 AM »
Hi Rob,

Not sure if this help:
http://clinicaltrials.gov/ct2/show/NCT01013987

Best Wishes
Talk to you soon,

John

Offline mercuryman

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #8 on: February 05, 2010, 05:52:21 AM »
John,

I have very little sensitivity to Darunavir; I'm resistant to Isentress; and Selzentry does nothing for me (without having an X4 drug to use as well) due to the fact that I'm dual-tropic.

Too, the study site for this trial is in Argentina....

Although, I do look forward to visiting Argentina one day.  :)

Thank you for your response and I'm sure we will converse more soon.

Rob

Offline veritas

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #9 on: February 05, 2010, 06:29:34 AM »

Rob,

Yea, monotherapy with Isentress is not good due to the low barrier to resistance.

Another med to watch to increase cd4 cells is Il7. See this:

http://www.aidsinfo.nih.gov/ClinicalTrials/search.aspx?drugName=IL7

My meds include: Isentress, Prezista/norvir, Truvada -- so far so good,it's holding up for me.

Rob, keep up the search, there will be more clinical trials. I know the wait seems endless, but it will happen.

v

Offline mercuryman

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #10 on: February 05, 2010, 10:00:08 AM »
V,

Yes, I have read about IL-7.......unfortunately, at this point, I do not qualify for any of the current trials. I think I will call a clinical coordinator to determine when a new HIV trial/study for IL-7 is planned.......It always helps to have a "Plan B".

I'm glad that your current regimen is working well for you......and it is user friendly as well (not many side effects).

Thanks you for the info you provided......

The Eternal Optimist.......

Rob

Offline mercuryman

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #11 on: February 25, 2010, 08:22:25 PM »
An update.....
Unfortunately, I was NOT able to enroll in the Ibalizumab study......The study requires one to have at least 1 other FULLY ACTIVE agent in their OBT. Initially, I thought that drug would be Etravirine......An older genotype showed several mutations which would make Etravirine much less effective.......hence, I would also eventually develop resistance to Ibalizumab.......so the drug company denied my enrollment.

Also, after the 24 week study with Ibalizumab, the drug company (TaiMed Biologics) would still offer the drug for free; however, I would then have to pay for nursing services/cost of infusion, which would come up to about $800.00/month.......on top of the time spent going in for the infusion every two weeks........I can live without all that stress! Now to find a new plan of attack for my very resistant/dual tropic virus!

Have a good evening.....

Rob

Offline Inchlingblue

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Re: Ibalizumab (TNX-355 or now TMB-202); Any knowledge/experience with?
« Reply #12 on: February 25, 2010, 10:15:54 PM »
Can you get into any of the trials for Gilead's Quad?

Also, here is some information about a bevirimat trial that's recruiting:

MPC-4326 Maturation Inhibitor Trial Now Enrolling

Myriad Pharmaceuticals has announced that enrollment in its Phase 2 study of MPC-4326 is now open. MPC-4326, formerly known as bevirimat, is in an entirely new class of drugs called maturation inhibitors, which target the virus after is has “matured” and during the “budding” process of the HIV life cycle (see “HIV and your Immune System” in the September/October 2009 issue). There is currently no maturation inhibitor yet on the market, and the unique mechanism of action for MPC-4326 may make this drug useful for those failing their current regimen due to drug resistance.

For more detailed information, including a list of study sites, and to see whether you would eligible for the study, go to


http://clinicaltrials.gov/ct2/show/NCT01026727?term=mpc-4326&rank=1.

Is it possible to cobble together a 3-drug regimen entirely made up of drugs in clinical trials?
« Last Edit: February 27, 2010, 01:59:29 PM by Inchlingblue »

 


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