Aa
The second wave of "Protease Drugs"
I have followd the data on this particular drug since it's inception and I feel it may be the next 'Protease" to hit the market ..before the all orals
Same type drug as Vic & Inci (taken with INF. /Riba) ,however data shows in PH 2 trial to be effective with 1) "only once a day dosing" 2)no fat requiements and 3)very few side effects.
Just some info as a tag on to hectors excellent linked Info below.
Will
Agents Undergoing Clinical Trials
Second-wave, First-generation Protease Inhibitors
The second wave of PIs for HCV includes agents with improved potency and dosing, but with resistance profiles that are similar to telaprevir and boceprevir. It is proposed that the term 'second-generation' PI be used for agents that have an improved resistance profile, such as several that are currently in development.
TMC435
TMC435 (Tibotec, Medivir Pharmaceuticals, Janssen, Raritan, NJ, USA) is a potent, noncovalent HCV NS3/4A protease inhibitor. In a phase IIa, double-blind, placebo-controlled trial of a treatment-naïve and treatment-experienced genotype 1 population, patients were randomized to two groups with a total of seven arms. The first group received TMC435 (25, 75 or 200 mg QD) or placebo (PBO) as a loading dose for a week followed by another 3 weeks of the PI and 24–48 weeks of PR. The second group received 4 weeks of the PI (25, 75 or 200 mg QD) or PBO in combination with PR for either 24 or 48 weeks. Viral load reduction in subjects in the second group who received the PI at 25, 75 or 200 mg QD with concurrent PR were −4.74, −5.52 and −5.44 log10 units, respectively. Grade 3/4 AEs were reported in 10–11% of subjects who received the 200-mg daily dose. The most common AEs were fatigue, nausea, influenza-like symptoms and headache. At 12 weeks, all patients who received the PI (75 or 200 mg) for 4 weeks + concurrent PR had HCV RNA <10 IU/mL.
The PILLAR study (Protease Inhibitor trial assessing the optimaL dose and duration as once daiLy Anti-viral Regimen) is an ongoing, 5-arm, global phase IIb randomized, double-blind, placebo-controlled study in 386 treatment-naïve patients. TMC435 was administered in doses of 75 mg or 150 mg QD for either 12 or 24 weeks in combination with 24 weeks of PR. Patients receiving TMC435 were allowed to stop all treatment at week 24 with HCV RNA levels <25 IU/mL at week 4 and HCV RNA <25 IU/mL at weeks 12, 16 and 20. Patients who did not meet criteria for a virologic response continued with PR for the full 48 weeks. TMC435 demonstrated potent antiviral activity, at week 4 (RVR) and at week 12 (cEVR) with 92%. HCV RNA was undetectable (<25 IU/mL) for the majority of patients; 83% of them were able to stop all treatment at week 24. The viral breakthrough rate was 4.9% in those who received the PI. Interim 24-week results from the stage IIb ASPIRE trial of TMC435 100 mg QD or 150 mg QD in combination with PR have revealed similar results in treatment-experienced patients infected with HCV genotype 1 who had previously received at least 1 course of PR. At week 24, with the higher dose of TMC435, HCV RNA was undetectable (<25 IU/mL) in 94% of relapsers, 89% of partial responders and 87% of nonresponders.[48] However, it should be noted that approximately 90% of the patient population in ASPIRE was white. As previously described, decreased viral responses are observed in black populations as compared with nonblack populations, which suggests that the patient population in ASPIRE is easier to treat than is a more representative cross-section of the total HCV patient population. Phase III studies in various stages of execution will examine safety and efficacy of the PI in treatment-naïve patients, relapsers and nonresponders.
Same type drug as Vic & Inci (taken with INF. /Riba) ,however data shows in PH 2 trial to be effective with 1) "only once a day dosing" 2)no fat requiements and 3)very few side effects.
Just some info as a tag on to hectors excellent linked Info below.
Will
Agents Undergoing Clinical Trials
Second-wave, First-generation Protease Inhibitors
The second wave of PIs for HCV includes agents with improved potency and dosing, but with resistance profiles that are similar to telaprevir and boceprevir. It is proposed that the term 'second-generation' PI be used for agents that have an improved resistance profile, such as several that are currently in development.
TMC435
TMC435 (Tibotec, Medivir Pharmaceuticals, Janssen, Raritan, NJ, USA) is a potent, noncovalent HCV NS3/4A protease inhibitor. In a phase IIa, double-blind, placebo-controlled trial of a treatment-naïve and treatment-experienced genotype 1 population, patients were randomized to two groups with a total of seven arms. The first group received TMC435 (25, 75 or 200 mg QD) or placebo (PBO) as a loading dose for a week followed by another 3 weeks of the PI and 24–48 weeks of PR. The second group received 4 weeks of the PI (25, 75 or 200 mg QD) or PBO in combination with PR for either 24 or 48 weeks. Viral load reduction in subjects in the second group who received the PI at 25, 75 or 200 mg QD with concurrent PR were −4.74, −5.52 and −5.44 log10 units, respectively. Grade 3/4 AEs were reported in 10–11% of subjects who received the 200-mg daily dose. The most common AEs were fatigue, nausea, influenza-like symptoms and headache. At 12 weeks, all patients who received the PI (75 or 200 mg) for 4 weeks + concurrent PR had HCV RNA <10 IU/mL.
The PILLAR study (Protease Inhibitor trial assessing the optimaL dose and duration as once daiLy Anti-viral Regimen) is an ongoing, 5-arm, global phase IIb randomized, double-blind, placebo-controlled study in 386 treatment-naïve patients. TMC435 was administered in doses of 75 mg or 150 mg QD for either 12 or 24 weeks in combination with 24 weeks of PR. Patients receiving TMC435 were allowed to stop all treatment at week 24 with HCV RNA levels <25 IU/mL at week 4 and HCV RNA <25 IU/mL at weeks 12, 16 and 20. Patients who did not meet criteria for a virologic response continued with PR for the full 48 weeks. TMC435 demonstrated potent antiviral activity, at week 4 (RVR) and at week 12 (cEVR) with 92%. HCV RNA was undetectable (<25 IU/mL) for the majority of patients; 83% of them were able to stop all treatment at week 24. The viral breakthrough rate was 4.9% in those who received the PI. Interim 24-week results from the stage IIb ASPIRE trial of TMC435 100 mg QD or 150 mg QD in combination with PR have revealed similar results in treatment-experienced patients infected with HCV genotype 1 who had previously received at least 1 course of PR. At week 24, with the higher dose of TMC435, HCV RNA was undetectable (<25 IU/mL) in 94% of relapsers, 89% of partial responders and 87% of nonresponders.[48] However, it should be noted that approximately 90% of the patient population in ASPIRE was white. As previously described, decreased viral responses are observed in black populations as compared with nonblack populations, which suggests that the patient population in ASPIRE is easier to treat than is a more representative cross-section of the total HCV patient population. Phase III studies in various stages of execution will examine safety and efficacy of the PI in treatment-naïve patients, relapsers and nonresponders.
http://clinicaltrials.gov/ct2/results?term=gs-us-256-0124
This is the Gilead trial GS-US-256-0124. We were treating with the new wave of once daily protease. Check out the trial on clinicaltrials.gov. Best of luck and keep us posted.
What Gilead trial were you in?
I am being considered for the Gl 7977 and TMC 435 trail . Thinking about it now and wondering what happens if i fail. Previous non responder GT 1a
I am being considered for the Gl 7977 and TMC 435 trail . Thinking about it now and wondering what happens if i fail. Previous non responder GT 1a
I too was in the gilead trial that no whine was in and failed after six months. Could never get the last 100 viral load to go. Since I failed soc twice before and am la ct and considered a non responder it was no use to continue. In the trial at my hospital only two people out of 10 went undetected all the non responders failed. They started running the 9777 all oral trial in March which has been very successful. I am hoping to get into another trial in the future with that one. I also do 3 monthly resistance testing and follow up but no information is given to me. But it does keep me in the loop. Which I had done 9777, but I was already in a trail,
They don't tell me "jack" about my blood test every 3 months. They also do general LFT to monitor me and will let me know if things get too abnormal....so far so good. I'm told they study the blood work for resistant mutations returning to wild type and they freeze and store some for possible future study. Maybe this will help me and others for future treatments. I also get to check in with the doc., as they do a short physical, and ask about new trails treatments etc. Best of luck to all.
I think you're NP is giving you bad information. The only approved dosing for Victrelis is 3X daily. Only available as 200mg.
nowhine
glad to see your input here. How have you been since you got off treatment? I hate to hear that you were the only failure in your trial group. That is depressing. I would be interested to know what they tell you about the PI resistance with your 3 month blood draws.
bean
glad to see your input here. How have you been since you got off treatment? I hate to hear that you were the only failure in your trial group. That is depressing. I would be interested to know what they tell you about the PI resistance with your 3 month blood draws.
bean
Just to add some more info. I was in a Gilead trial with a new once daily protease GS 9451 along with a NS5A- GS 5885, riba and interf. The side effects were consistent with my previous soc tx. No fat with the meds and the anemia seemed to be the same as with previous soc. Not a big deal to handle the treatment...rough but doable. The resistance factors to the new protease are similiar to Vic. and Inc. with 1a's having inherent resistant mutations. Also previous response to inter. is a large factor to success, or SVR. Although I failed the treatment all others at my doc are und. and in process of completing the soc portion of the trail. There are others on this forum that are currently und. I am also in a follow -up registry trial with Gilead where I give blood every 3 months so they can follow the resistant mutations. I know it is common practice to not try another PI if one has failed with a PI. Best of luck to all.
Will, this is wonderful news. As it is now, if it weren't for the side effects, these current PI's would be perfect. But the side effects are sidelining too many of us. If the second phase can reduce those sx I am all for them. In the body of the text where it discusses AE's (adverse effects) I don't even see anemia listed.Wow.
Pooh -- CCO (Clinical Care Options) has an excellent presentation of PI resistance. I don't have the link on my office computer but will try to get it to you - either in this thread or pm this evening. Remind me if I forget.
will and jules -- I wish you could both wait for these second round drugs. They do sound so much better.
bean
Pooh -- CCO (Clinical Care Options) has an excellent presentation of PI resistance. I don't have the link on my office computer but will try to get it to you - either in this thread or pm this evening. Remind me if I forget.
will and jules -- I wish you could both wait for these second round drugs. They do sound so much better.
bean
Just wanted to let you know I saw my NP about classes for injection and meds. While we were talking she mentioned that Vic now has a pill that you only take one in the am and one in the pm, instead of three. She said that was the reason my Vic was originally denied for ins coverage because that is the one she applied for. The ins co said it was too expensive and would not cover it but they would cover the three pills. So I guess it costs more to make one pill than three pills (Ha what a joke)!
Will, Stormy and 1swimmwe:
Thanks! I am definitely very optimistic I but don't want to be too overconfident or cavalier. And, I always like to have Plan B and Plan C in the wings in case Plan A does not work.
Thanks! I am definitely very optimistic I but don't want to be too overconfident or cavalier. And, I always like to have Plan B and Plan C in the wings in case Plan A does not work.
First of all you are not going to fail !
However let me say this. This drug is one of the second wave of the same type that INCI &Vic are ,attacks the "protease " of the virus.
The resistance issues currently is a grey area that they just don't seem to have the full handle on yet but are working on it because as we know some will fail these two drugs(again not you)
Because this is the same class a doctor most likely "would not" want to try another protease because of this.
Plus it would be like basically trying the same thing again and what is the point.
The interesting thing is that if one fails a protease it very often is their "insensitivity to the Interferon that is the problem and in cases of protease failures it would most likely be best to wait until INF free is on the market.
This is all a moot point for my friend pooh tho :)
Will
However let me say this. This drug is one of the second wave of the same type that INCI &Vic are ,attacks the "protease " of the virus.
The resistance issues currently is a grey area that they just don't seem to have the full handle on yet but are working on it because as we know some will fail these two drugs(again not you)
Because this is the same class a doctor most likely "would not" want to try another protease because of this.
Plus it would be like basically trying the same thing again and what is the point.
The interesting thing is that if one fails a protease it very often is their "insensitivity to the Interferon that is the problem and in cases of protease failures it would most likely be best to wait until INF free is on the market.
This is all a moot point for my friend pooh tho :)
Will
Those drugs sound promising. If I happen to fail this treatment, will I be able to treat with them or will they have the same resistance issues that would cause me to fail this treatment. Just curious. I have to keep all options lined up just in case.
"Same type drug as Vic & Inci (taken with INF. /Riba) ,however data shows in PH 2 trial to be effective with 1) "only once a day dosing" 2)no fat requiements and 3)very few side effects. "
Taken with interferon and riba.
Taken with interferon and riba.
" Same type drug as Vic & Inci (taken with INF. /Riba) ,however data shows in PH 2 trial to be effective with 1) "only once a day dosing" 2)no fat requiements and 3)very few side effects. "
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That would absolutely be amazing! Thanks for posting Will
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That would absolutely be amazing! Thanks for posting Will
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