Moved this one from pre-clinical to phase I.
Millennium Announces Phase I Trial of MLN0415 for Inflammatory Disorders
August 30, 2006 -- PRNewswire-FirstCall -- Millennium Pharmaceuticals today announced the initiation of a Phase I study of MLN0415, an oral, highly selective, small molecule inhibitor of IKK2, which targets a major inflammatory pathway. The randomized, double-blind, placebo-controlled study will enroll up to 72 healthy volunteers and assess safety, tolerability, pharmacokinetic and pharmacodynamic effects. MLN0415 has a unique mechanism of action that has the potential to address multiple inflammatory disorders including rheumatoid arthritis and multiple sclerosis.
"MLN0415, a new molecule discovered by Millennium scientists, selectively targets a key pathway involved in inflammatory response, which makes it an attractive product candidate for preventing or delaying disease progression," said Nancy Simonian, M.D., Senior Vice President, Clinical, Medical and Regulatory Affairs, Millennium. "We continue to advance novel molecules into the clinic and this study is part of a larger inflammatory development program that includes five product candidates."
MLN0415 is a novel, small molecule IKK2 inhibitor, discovered by Millennium scientists. In preclinical studies, MLN0415 was shown to decrease NF-kB activation and down-regulate the expression of a number of inflammatory proteins. Because inflammatory proteins play a critical role in inflammation and drive the inflammatory response to disease, controlling these proteins may prevent or slow disease progression.
Millennium and sanofi-aventis have an alliance focused on developing and commercializing small molecule drugs for the treatment of inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. MLN0415 is one of several small molecules that are part of this collaboration, three of which are in the clinic.
http://biz.yahoo.com/prnews/060830/new007.html?.v=70
Summary of the pipeline
One I've never heard of before. It doesn't say what phase, but if it's looking at disease activity, I'll assume phase II.
A Randomized, Double-Blind, Placebo-Controlled, Parallel Groups Study to Assess the Effects of L-000124467 on Disease Activity in Patients with Relapsing-Remitting Multiple Sclerosis as Measured by MRI
Location: Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai Medical Center, 5 East 98th Street, Box 1138, New York, NY 10029.
Purpose: The purpose of this study is to evaluate the safety and effectiveness of a new investigational drug, L000124467 that is being studied for the treatment of relapsing-remitting multiple sclerosis (MS) and to examine the effects of this drug. L000124467 is an experimental drug that has not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory authority. Neither you nor the study doctor will know what medication you are receiving.
Eligibility: To participate we are searching for male and female volunteers 18 to 55 years old with relapsing-remitting MS or subjects who have had one attack in the past year and are not yet diagnosed with MS (This is called a Clinically Isolated Syndrome). Subjects cannot be on a current MS therapy. You cannot participate if you are pregnant or planning a pregnancy and must practice two forms of birth control. Medications, evaluations, and tests will be paid for by the study. You must meet entry criteria.
Procedure: This study requires that you make at least seven visits to the clinic for clinical assessments over a 4-month period.
Benefit: Medications, evaluations, and tests will be provided by the study. Subjects will be reimbursed for transportation and time expenses for $100 each visit. The benefits from your participation in this study include the possibility of making a contribution to medical knowledge, which may help other people with MS, and the possibility of treating your multiple sclerosis.
Contact Information: Drs. Mark Tullman, Fred Lublin and Aaron Miller are involved in this project. If you are interested or would like more information about this clinical research study, please contact Michele Weber, Clinical Research Coordinator at (212) 241-4264 or at multiple.sclerosis@mssm.edu.
<shortened url>
A Randomized, Double-Blind, Placebo-Controlled, Parallel Groups Study to Assess the Effects of L-000124467 on Disease Activity in Patients with Relapsing-Remitting Multiple Sclerosis as Measured by MRI
Location: Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Mount Sinai Medical Center, 5 East 98th Street, Box 1138, New York, NY 10029.
Purpose: The purpose of this study is to evaluate the safety and effectiveness of a new investigational drug, L000124467 that is being studied for the treatment of relapsing-remitting multiple sclerosis (MS) and to examine the effects of this drug. L000124467 is an experimental drug that has not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory authority. Neither you nor the study doctor will know what medication you are receiving.
Eligibility: To participate we are searching for male and female volunteers 18 to 55 years old with relapsing-remitting MS or subjects who have had one attack in the past year and are not yet diagnosed with MS (This is called a Clinically Isolated Syndrome). Subjects cannot be on a current MS therapy. You cannot participate if you are pregnant or planning a pregnancy and must practice two forms of birth control. Medications, evaluations, and tests will be paid for by the study. You must meet entry criteria.
Procedure: This study requires that you make at least seven visits to the clinic for clinical assessments over a 4-month period.
Benefit: Medications, evaluations, and tests will be provided by the study. Subjects will be reimbursed for transportation and time expenses for $100 each visit. The benefits from your participation in this study include the possibility of making a contribution to medical knowledge, which may help other people with MS, and the possibility of treating your multiple sclerosis.
Contact Information: Drs. Mark Tullman, Fred Lublin and Aaron Miller are involved in this project. If you are interested or would like more information about this clinical research study, please contact Michele Weber, Clinical Research Coordinator at (212) 241-4264 or at multiple.sclerosis@mssm.edu.
<shortened url>
timelines?
Hey Dignan,
My neuro says that there will be new meds out in "a year or two" (not including FDA approval times, I'll bet.) I don't follow the pipeline as closely as you do and she may be being optimistic. Would you whip out your crystal ball and tell me abt the offical timelines for any of the 13 Phase III options?
Lee
My neuro says that there will be new meds out in "a year or two" (not including FDA approval times, I'll bet.) I don't follow the pipeline as closely as you do and she may be being optimistic. Would you whip out your crystal ball and tell me abt the offical timelines for any of the 13 Phase III options?
Lee
Lee,
Dignan may well have a different view, but I don't see any new meds arriving much before 2010. I have seen this date mentioned for FTY720. The FDA have already had their fingers burned with fast-tracking Tysabri so may not do the same for other drugs, even if they show real promise.
I suppose the two which might come in a bit earlier are Campath and Rituxan. Both drugs are already approved for other diseases (cancer) so have a history and known safety profile. Rituxan was fairly recently approved for RA. The phase III Rituxan trial is for PP MS where there are no real treatment options. I imagine that if it appears to slow disease progression it might be made available more quickly than normal.
New formula Rebif might get through on a quicker timescale. But as far as I understand it is about making it easier for patients to take etc rather than any improved effectiveness. One of my neuros (Dr Giovannoni) is giving a presentation on new formula Rebif at the ECTRIMS conference at the end of September. And the conference includes numerous presentations on the drugs in trial, such as FTY720.
I've been surprised at how the CRAB drugs have never been improved. Perhaps with so much competition Biogen will continue to develop Tysabri and we will see a better / safer Tysabri in years to come!
In addition to the drugs listed in Phase III, there are other trials involving drugs such as minocycline, statins and hormones e.g. testosterone. The outcome of these trial should be known in the next 12-18 months (guess). If the results are good we may be adding one or more of them to our current drug. So in the future, in addition to your Tysabri, you may take a statin, put on a blob of testosterone and take a Vit D supplement!
Dignan may have other views about the timescale for introduction of the Phase III drugs.
All the best
Ian
Dignan may well have a different view, but I don't see any new meds arriving much before 2010. I have seen this date mentioned for FTY720. The FDA have already had their fingers burned with fast-tracking Tysabri so may not do the same for other drugs, even if they show real promise.
I suppose the two which might come in a bit earlier are Campath and Rituxan. Both drugs are already approved for other diseases (cancer) so have a history and known safety profile. Rituxan was fairly recently approved for RA. The phase III Rituxan trial is for PP MS where there are no real treatment options. I imagine that if it appears to slow disease progression it might be made available more quickly than normal.
New formula Rebif might get through on a quicker timescale. But as far as I understand it is about making it easier for patients to take etc rather than any improved effectiveness. One of my neuros (Dr Giovannoni) is giving a presentation on new formula Rebif at the ECTRIMS conference at the end of September. And the conference includes numerous presentations on the drugs in trial, such as FTY720.
I've been surprised at how the CRAB drugs have never been improved. Perhaps with so much competition Biogen will continue to develop Tysabri and we will see a better / safer Tysabri in years to come!
In addition to the drugs listed in Phase III, there are other trials involving drugs such as minocycline, statins and hormones e.g. testosterone. The outcome of these trial should be known in the next 12-18 months (guess). If the results are good we may be adding one or more of them to our current drug. So in the future, in addition to your Tysabri, you may take a statin, put on a blob of testosterone and take a Vit D supplement!
Dignan may have other views about the timescale for introduction of the Phase III drugs.
All the best
Ian
Last edited by bromley on Thu Sep 07, 2006 11:04 am, edited 1 time in total.
Crystal ball...crystal ball...I seem to have mislaid my crystal ball. I'm not going to track things down for this response, this will just be off the top of my head, hope that's alright. I should start by saying I assume Bromely is right that after the Tysabri episode, regulators around the world won't be eager to approve anything on one year data, two years will probably be required (not that I have any special knowledge of this). Could it also be that your doctor is expecting statin or antibiotic trials to be positive so they could be prescribed (not just off-label) for MS?
1. Betaseron (500 mcg dose) (Schering) -- I think we'll be hearing about results in 2007, might not be available until 2008
2. BG12 (Biogen) -- just getting the phase III up and running now I think, so it wouldn't possibly be available until late 2009, but probably more like 2010/2011
3. Campath (aka alemtuzumab) (Genzyme) -- The phase III ran into some side-effect concerns about a year ago, but I think things are getting back on track, so could be available in 2009.
4. Copaxone (40mg dose) (Teva) -- 2008 or 2009
5. FTY720 (aka fingolimod) (Novartis) -- They've been recruiting on this one since last year in Europe, but just starting up now in N. Am., so could be 2009 in Europe, 2010 in N. Am.
6. MBP8298 (BioMS) (trial for SPMS) -- have enrolled just over 300 out of total of 550 patients in phase III, so probably 2009 or 2010.
7. Mycophenolate mofetil (aka Cellcept) (with Avonex) -- Not sure if it has officially started yet or not, so probably 2009/2010, although Cellcept is already used off-label
8. Mylinax (oral cladribine) (Serono) -- This one and teriflunomide are probably neck and neck in the battle to be the first pill approved for RRMS in N. Am., but I don't imagine approval until the end of 2008 at the earliest, probably 2009.
9. Progestin and Estradiol (Hospices Civils de Lyon) -- This one started in 2005 I think, so could be completed in 2008 or 2009.
10. Rebif (fetal bovine serum-free/human serum albumin-free) (Serono) -- As Bromley said, they are presenting results soon, so if all goes well, it could be available by the end of 2006, or early 2007
11. Rituximab (aka Rituxan) (Biogen / Genentech) (primary progressive MS trial) -- probably 2009, although as Bromley said, since it's for PPMS, it's possible this could get early approval if it is really effective.
12. Stem cells - autologous hematopoietic (HSCT) -- I don't have a good reference on this, I read that there are phase III trials of HSCT going on in Europe, but I don't know any details and the N. Am. trials are in phase II still, so it could be 2008 if the European trials are progressing well, or if not, it could be more like 2011/12 in N. Am.
13. Teriflunomide (aka HMR 1726) (Sanofi-Aventis) -- See Mylinax above, could be late 2008.
I'm guessing that the new versions of the CRABs could be approved over the next 2 years, but other than that, we will have to wait until 2009 for anything new to be approved.
1. Betaseron (500 mcg dose) (Schering) -- I think we'll be hearing about results in 2007, might not be available until 2008
2. BG12 (Biogen) -- just getting the phase III up and running now I think, so it wouldn't possibly be available until late 2009, but probably more like 2010/2011
3. Campath (aka alemtuzumab) (Genzyme) -- The phase III ran into some side-effect concerns about a year ago, but I think things are getting back on track, so could be available in 2009.
4. Copaxone (40mg dose) (Teva) -- 2008 or 2009
5. FTY720 (aka fingolimod) (Novartis) -- They've been recruiting on this one since last year in Europe, but just starting up now in N. Am., so could be 2009 in Europe, 2010 in N. Am.
6. MBP8298 (BioMS) (trial for SPMS) -- have enrolled just over 300 out of total of 550 patients in phase III, so probably 2009 or 2010.
7. Mycophenolate mofetil (aka Cellcept) (with Avonex) -- Not sure if it has officially started yet or not, so probably 2009/2010, although Cellcept is already used off-label
8. Mylinax (oral cladribine) (Serono) -- This one and teriflunomide are probably neck and neck in the battle to be the first pill approved for RRMS in N. Am., but I don't imagine approval until the end of 2008 at the earliest, probably 2009.
9. Progestin and Estradiol (Hospices Civils de Lyon) -- This one started in 2005 I think, so could be completed in 2008 or 2009.
10. Rebif (fetal bovine serum-free/human serum albumin-free) (Serono) -- As Bromley said, they are presenting results soon, so if all goes well, it could be available by the end of 2006, or early 2007
11. Rituximab (aka Rituxan) (Biogen / Genentech) (primary progressive MS trial) -- probably 2009, although as Bromley said, since it's for PPMS, it's possible this could get early approval if it is really effective.
12. Stem cells - autologous hematopoietic (HSCT) -- I don't have a good reference on this, I read that there are phase III trials of HSCT going on in Europe, but I don't know any details and the N. Am. trials are in phase II still, so it could be 2008 if the European trials are progressing well, or if not, it could be more like 2011/12 in N. Am.
13. Teriflunomide (aka HMR 1726) (Sanofi-Aventis) -- See Mylinax above, could be late 2008.
I'm guessing that the new versions of the CRABs could be approved over the next 2 years, but other than that, we will have to wait until 2009 for anything new to be approved.
Thanks you guys...I heard a visiting neuro (sorry I have ms so I can't remember his name) last year talking abt the trials using double doses of Betaseron and thought perhaps it might come along a little sooner but I have been sooooo fucused on Tysabri for so long that I really didn't know what to hope for next and since hope is such a big part of my regimen...
Off the top of one's head is great for wishful thinking.
Lee
Off the top of one's head is great for wishful thinking.
Lee
ABT-874
My wife, who was in the ABT-874 study, was just informed that it is being cancelled. She was told that the results are good, but nothing that would blow away “other things out there.”
Anyway,
1) Dignan should probably remove it from the list. Or at least, move it to something different?
2) Any advice on other studies/remedies? We just moved to Hartford, Connecticut. The closest ABT-874 office is in Albany, NY and she was willing to drive two hours there, though, I’d rather not have her drive that far for medication. Outside of general joint/muscle/head aches and pains, she is mostly symptom free and has not had an episode in the last calendar year, and only one in the last two. (Guess, by MS standards, that makes her lucky.) Anyway, that may disqualify her from most studies. We have insurance through my employment, so money is not a major concern. However, she is doing it more in hope of finding something out there that is better than what a doctor would prescribe. I’d prefer a phase III or a later stage phase II. She is a former research scientist for Abbot and Parke-Davis (now Pfiser). So, she is great about following protocols and probably feels more comfortable with being in and believing in studies than most.
-Gary
Anyway,
1) Dignan should probably remove it from the list. Or at least, move it to something different?
2) Any advice on other studies/remedies? We just moved to Hartford, Connecticut. The closest ABT-874 office is in Albany, NY and she was willing to drive two hours there, though, I’d rather not have her drive that far for medication. Outside of general joint/muscle/head aches and pains, she is mostly symptom free and has not had an episode in the last calendar year, and only one in the last two. (Guess, by MS standards, that makes her lucky.) Anyway, that may disqualify her from most studies. We have insurance through my employment, so money is not a major concern. However, she is doing it more in hope of finding something out there that is better than what a doctor would prescribe. I’d prefer a phase III or a later stage phase II. She is a former research scientist for Abbot and Parke-Davis (now Pfiser). So, she is great about following protocols and probably feels more comfortable with being in and believing in studies than most.
-Gary
Gary,
Sorry to hear about ABT-874. I imagine that drugs in trial will need to show that they can better the efficacy of the current CRAB drugs and match or better the likes of Tysabri.
A possible Phase III which is to start soon is Rituxan for RR (Phase II preliminary results just released). One of my neuros who is highly regarded thinks that Rituxan looks very promising. I suppose the only issue is the placebo arm. Another option is Tovaxin - the company is recruting for Phase III (I think).
It may be worth waiting until the end of the month as many trial results will be highlighted at the ECTRIMS conference. Also, Biogen are to provide more details on the Rituxan trial in the near future.
Hope this helps
Ian
Sorry to hear about ABT-874. I imagine that drugs in trial will need to show that they can better the efficacy of the current CRAB drugs and match or better the likes of Tysabri.
A possible Phase III which is to start soon is Rituxan for RR (Phase II preliminary results just released). One of my neuros who is highly regarded thinks that Rituxan looks very promising. I suppose the only issue is the placebo arm. Another option is Tovaxin - the company is recruting for Phase III (I think).
It may be worth waiting until the end of the month as many trial results will be highlighted at the ECTRIMS conference. Also, Biogen are to provide more details on the Rituxan trial in the near future.
Hope this helps
Ian
I will axe ABT-874. That's too bad. I think the Tovaxin trial Bromley mentioned is actually a phase IIB trial.
Your wife knows more about this than I do, but I'm a bit torn about which phase is best to participate in. Phase III gives you better odds that it's effective, but on the other hand since all phase III and most phase II trials are placebo controlled, in a phase II trial you would potentially be on placebo for a shorter duration, and then possibly put on the trial drug upon successful conclusion of the trial.
Your wife knows more about this than I do, but I'm a bit torn about which phase is best to participate in. Phase III gives you better odds that it's effective, but on the other hand since all phase III and most phase II trials are placebo controlled, in a phase II trial you would potentially be on placebo for a shorter duration, and then possibly put on the trial drug upon successful conclusion of the trial.
Another pre-clinical...HE3204
Hollis-Eden Pharmaceuticals Presents Data Demonstrating Potential Therapeutic Benefits of Second-Generation Drug Candidates
September 12, 2006 - BUSINESS WIRE - Hollis-Eden Pharmaceuticals announced today that it is presenting preclinical data at the 12th International Congress on Hormonal Steroids, Hormones & Cancer being held September 13-16, 2006, in Athens, Greece, demonstrating indication-specific activity and potential therapeutic benefits of multiple second-generation compounds derived from the Company's Hormonal Signaling Technology Platform.
As reported at the meeting, the compounds described include potential drug candidates that are effective and non-toxic in animal models of multiple sclerosis, rheumatoid arthritis, diabetes, prostate cancer and chemotherapy recovery. In addition, the Company reported that it has made significant progress in defining the mechanisms of action of its Hormonal Signaling Technology Platform. Specifically, several second-generation Hollis-Eden compounds regulate NF-kappaB, a protein that plays a key role in cellular signaling. NF-kappaB activation leads to the production of inflammatory mediators such as TNF-alpha, IL-6, and IFN-gamma, and controls various other cellular functions. Thus, NF-kappaB is an important pharmaceutical target for treatment of inflammatory and metabolic disorders.
Hollis-Eden's Hormonal Signaling Technology Platform comprises a proprietary new class of small molecule compounds that are designed to restore the biological activity of cellular signaling pathways disrupted by disease and aging. Through years of research with these compounds -- metabolic conversions or synthetic analogs of adrenal steroid hormones -- Hollis-Eden has made significant discoveries relating to their metabolism, mechanism of action and pharmacologic profile.
First-generation drug candidates from this class of compounds have been demonstrated in humans to have three core therapeutic properties: they regulate innate and adaptive immunity, reduce unproductive inflammation, and stimulate the proliferation of progenitor cells in the bone marrow that may play a role in regenerative medicine. Second-generation compounds are designed to have improved pharmaceutical acceptability while retaining the potent anti-inflammatory and specific immune regulatory properties observed with first-generation compounds. Hollis-Eden is leveraging its Hormonal Signaling Technology Platform through multiple development programs now yielding second-generation development candidates that may be developed by the Company independently or through collaborations with other pharmaceutical companies.
Autoimmunity and Inflammatory Conditions
In its autoimmune program, Hollis-Eden reported that it has developed orally available compounds -- HE3204 and HE3286 -- that demonstrate anti-inflammatory activity without immunosuppression.
-- In vitro, HE3204 and HE3286 inhibited NF-kappaB signal transduction pathways at concentrations lower than that of the widely used corticosteroid dexamethasone.
-- In a LPS-stimulated mouse model of inflammation, HE3204 decreased activated NF-kappaB in the spleen and TNF-alpha in the blood.
-- In a preclinical model of multiple sclerosis, a cell-mediated (Th1) autoimmune disorder, orally administered HE3204 decreased disease and decreased the production of antigen-specific responses of TNF-alpha, IL-6 and the Th1 cytokine IFN-gamma.
-- In a preclinical model of rheumatoid arthritis, an antibody-mediated (Th2) autoimmune disorder, orally administered HE3286 decreased joint swelling scores and increased the production of antigen-specific IFN-gamma and TNF-alpha responses in the spleen, indicative of a shift away from Th2 responses and toward cell-mediated (Th1) immunity.
-- Both compounds have shown good oral bioavailability in primates.
-- Neither compound is immunosuppressive in a number of in vitro and in vivo immune-stimulation assays.
<shortened url>
Hollis-Eden Pharmaceuticals Presents Data Demonstrating Potential Therapeutic Benefits of Second-Generation Drug Candidates
September 12, 2006 - BUSINESS WIRE - Hollis-Eden Pharmaceuticals announced today that it is presenting preclinical data at the 12th International Congress on Hormonal Steroids, Hormones & Cancer being held September 13-16, 2006, in Athens, Greece, demonstrating indication-specific activity and potential therapeutic benefits of multiple second-generation compounds derived from the Company's Hormonal Signaling Technology Platform.
As reported at the meeting, the compounds described include potential drug candidates that are effective and non-toxic in animal models of multiple sclerosis, rheumatoid arthritis, diabetes, prostate cancer and chemotherapy recovery. In addition, the Company reported that it has made significant progress in defining the mechanisms of action of its Hormonal Signaling Technology Platform. Specifically, several second-generation Hollis-Eden compounds regulate NF-kappaB, a protein that plays a key role in cellular signaling. NF-kappaB activation leads to the production of inflammatory mediators such as TNF-alpha, IL-6, and IFN-gamma, and controls various other cellular functions. Thus, NF-kappaB is an important pharmaceutical target for treatment of inflammatory and metabolic disorders.
Hollis-Eden's Hormonal Signaling Technology Platform comprises a proprietary new class of small molecule compounds that are designed to restore the biological activity of cellular signaling pathways disrupted by disease and aging. Through years of research with these compounds -- metabolic conversions or synthetic analogs of adrenal steroid hormones -- Hollis-Eden has made significant discoveries relating to their metabolism, mechanism of action and pharmacologic profile.
First-generation drug candidates from this class of compounds have been demonstrated in humans to have three core therapeutic properties: they regulate innate and adaptive immunity, reduce unproductive inflammation, and stimulate the proliferation of progenitor cells in the bone marrow that may play a role in regenerative medicine. Second-generation compounds are designed to have improved pharmaceutical acceptability while retaining the potent anti-inflammatory and specific immune regulatory properties observed with first-generation compounds. Hollis-Eden is leveraging its Hormonal Signaling Technology Platform through multiple development programs now yielding second-generation development candidates that may be developed by the Company independently or through collaborations with other pharmaceutical companies.
Autoimmunity and Inflammatory Conditions
In its autoimmune program, Hollis-Eden reported that it has developed orally available compounds -- HE3204 and HE3286 -- that demonstrate anti-inflammatory activity without immunosuppression.
-- In vitro, HE3204 and HE3286 inhibited NF-kappaB signal transduction pathways at concentrations lower than that of the widely used corticosteroid dexamethasone.
-- In a LPS-stimulated mouse model of inflammation, HE3204 decreased activated NF-kappaB in the spleen and TNF-alpha in the blood.
-- In a preclinical model of multiple sclerosis, a cell-mediated (Th1) autoimmune disorder, orally administered HE3204 decreased disease and decreased the production of antigen-specific responses of TNF-alpha, IL-6 and the Th1 cytokine IFN-gamma.
-- In a preclinical model of rheumatoid arthritis, an antibody-mediated (Th2) autoimmune disorder, orally administered HE3286 decreased joint swelling scores and increased the production of antigen-specific IFN-gamma and TNF-alpha responses in the spleen, indicative of a shift away from Th2 responses and toward cell-mediated (Th1) immunity.
-- Both compounds have shown good oral bioavailability in primates.
-- Neither compound is immunosuppressive in a number of in vitro and in vivo immune-stimulation assays.
<shortened url>
Thank you, Ian and dignan.
Don't know if she knows more about it. She was more in the early stages of screening compounds, not in the very last stages of human trials.
In the end it is a very human, non quantitative, decision anyway.
You are right, placebo is a risk. If it's for half a year or a year, there is more of an incentive to participate than something like three.
Of course, if there was a drug that was promising to be a cure all. Many people would jump even if placebo arm was two thirds of the sample.
Anyway, we need to start doing more homework on what's out there.
-Gary
Don't know if she knows more about it. She was more in the early stages of screening compounds, not in the very last stages of human trials.
In the end it is a very human, non quantitative, decision anyway.
You are right, placebo is a risk. If it's for half a year or a year, there is more of an incentive to participate than something like three.
Of course, if there was a drug that was promising to be a cure all. Many people would jump even if placebo arm was two thirds of the sample.
Anyway, we need to start doing more homework on what's out there.
-Gary
This is a new one on me.
A phase I trial of an interleukin-12/23 monoclonal antibody in relapsing multiple sclerosis.
Curr Med Res Opin. 2006 Sep;22(9):1671-8.
Kasper LH, Everitt D, Leist TP, Ryan KA, Mascelli MA, Johnson K, Raychaudhuri A, Vollmer T; The Multiple Sclerosis Investigators.
Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
OBJECTIVE: To assess the safety, tolerability and pharmacokinetics of an interleukin (IL)-12/23 monoclonal antibody (mAb) in subjects with a relapsing form of multiple sclerosis (MS).
METHODS: A phase I, double-blind, placebo-controlled, sequential dose escalation study was conducted in 20 subjects with MS. Subjects were randomized (4:1) to receive a single subcutaneous injection of either IL-12/23 mAb (0.3, 0.75, 1.5, and 3.0 mg/kg) or placebo. Clinical and laboratory evaluations were performed through 16 weeks following administration.
RESULTS: IL-12/23 mAb was well tolerated in this study. Adverse events were generally mild or moderate, with no apparent dose-related trends. One subject with a family history of breast cancer was diagnosed during the study with breast cancer 21 days after IL-12/23 mAb administration. There were no significant changes in laboratory indicators of systemic or neurotoxicity. There was a large degree of variability in T2 lesion volume and total number of gadolinium-positive lesions, both unaffected by dose escalation. Three relapses of MS occurred in two placebo-treated subjects. Over the range of single doses studied, the median T(max) ranged from 9.0 to 16.5 days, and the median T(1/2) ranged from 20.2 to 30.9 days.
CONCLUSION: Single subcutaneous administrations of IL-12/23 mAb in this first study of relapsing MS were generally well tolerated. Safety of the agent will need to be tested in a study of longer duration and involving a larger cohort of subjects.
<shortened url>
A phase I trial of an interleukin-12/23 monoclonal antibody in relapsing multiple sclerosis.
Curr Med Res Opin. 2006 Sep;22(9):1671-8.
Kasper LH, Everitt D, Leist TP, Ryan KA, Mascelli MA, Johnson K, Raychaudhuri A, Vollmer T; The Multiple Sclerosis Investigators.
Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
OBJECTIVE: To assess the safety, tolerability and pharmacokinetics of an interleukin (IL)-12/23 monoclonal antibody (mAb) in subjects with a relapsing form of multiple sclerosis (MS).
METHODS: A phase I, double-blind, placebo-controlled, sequential dose escalation study was conducted in 20 subjects with MS. Subjects were randomized (4:1) to receive a single subcutaneous injection of either IL-12/23 mAb (0.3, 0.75, 1.5, and 3.0 mg/kg) or placebo. Clinical and laboratory evaluations were performed through 16 weeks following administration.
RESULTS: IL-12/23 mAb was well tolerated in this study. Adverse events were generally mild or moderate, with no apparent dose-related trends. One subject with a family history of breast cancer was diagnosed during the study with breast cancer 21 days after IL-12/23 mAb administration. There were no significant changes in laboratory indicators of systemic or neurotoxicity. There was a large degree of variability in T2 lesion volume and total number of gadolinium-positive lesions, both unaffected by dose escalation. Three relapses of MS occurred in two placebo-treated subjects. Over the range of single doses studied, the median T(max) ranged from 9.0 to 16.5 days, and the median T(1/2) ranged from 20.2 to 30.9 days.
CONCLUSION: Single subcutaneous administrations of IL-12/23 mAb in this first study of relapsing MS were generally well tolerated. Safety of the agent will need to be tested in a study of longer duration and involving a larger cohort of subjects.
<shortened url>
-
scoobyjude
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