Based on this info, I will add Helminths to the phase II portion of the pipeline. I know Bob mentioned that the FDA was stalling this trial a few months back, but I'll add it anyway.
John O. Fleming, MD
University of Wisconsin, Madison, WI
Term/Amount: 4/1/05-3/31/07; $358,660
“Helminth-induced immunomodulation therapy (HINT) in relapsing-remitting MS”
A novel, pilot clinical trial testing whether ingestion of worm eggs has the potential to alter the immune attack in MS.
Scientists have noted that autoimmune diseases and allergies are less common in underdeveloped regions. Some researchers have noted that early exposure to common infectious agents, such as occurs to people in less developed regions, may stimulate the immune regulation in a positive way and aid healthy immune responses. Because MS is more prevalent in regions with high standards of hygiene, researchers are testing the idea that lack of exposure to common innocuous agents may cause the immune system to over-react and cause MS.
Studies in MS-like disease in lab rodents and preliminary clinical trials in Crohn’s disease, an autoimmune disease of the bowel, suggest that eating eggs from the harmless parasitic worm (called helminth) might alter immune attacks and improve these conditions. Based on these and other studies, John Fleming, MD, is conducting a small clinical trial to test the potential of oral helminth eggs for improving relapsing-remitting MS. After the innocuous eggs are ingested in a sports drink, they hatch into larvae. When they reach the large intestine, the larvae interact with the immune system and are then killed. This interaction may have a positive impact on immune responses. Dr. Fleming’s team is using MRI and other testing protocols over ten months of treatment to determine whether participants show any signs of benefit.
This cutting-edge research should provide important information as to whether this unique therapy has the potential to benefit those with MS.
http://www.nationalmssociety.org/Research-fleming.asp
Summary of the pipeline
I'm always happy to see new stem cell studies...
Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS)
This study is not yet open for patient recruitment.
Verified by University of Cambridge November 2006
Sponsors and Collaborators: University of Cambridge
Purpose
Hypothesis: Intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells is a safe novel therapeutic approach for patients with multiple sclerosis
Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) is a phase I/IIA trial designed to establish the safety of intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells to patients with multiple sclerosis.
Procedure: Intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells
Phase I / Phase II
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Crossover Assignment, Safety/Efficacy Study
Further study details as provided by University of Cambridge:
Primary Outcomes: Adverse events
Secondary Outcomes: Visual function (acuity and colour); Visual evoked potential latency; Optic nerve Magnetisation Transfer Ratio; Retinal nerve fibre layer thickness (by optical coherence tomography); Brain lesion Magnetisation Transfer Ratio; MRI brain T1 hypointensity load; T cell response suppression; Multiple Sclerosis Functional Composite Score; Expanded Kurtzke Disability Status Score
Expected Total Enrollment: 20
Design: 1 year cross over, single treatment at 6 months
http://www.clinicaltrials.gov/ct/show/N ... 0?order=13
Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS)
This study is not yet open for patient recruitment.
Verified by University of Cambridge November 2006
Sponsors and Collaborators: University of Cambridge
Purpose
Hypothesis: Intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells is a safe novel therapeutic approach for patients with multiple sclerosis
Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) is a phase I/IIA trial designed to establish the safety of intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells to patients with multiple sclerosis.
Procedure: Intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells
Phase I / Phase II
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Crossover Assignment, Safety/Efficacy Study
Further study details as provided by University of Cambridge:
Primary Outcomes: Adverse events
Secondary Outcomes: Visual function (acuity and colour); Visual evoked potential latency; Optic nerve Magnetisation Transfer Ratio; Retinal nerve fibre layer thickness (by optical coherence tomography); Brain lesion Magnetisation Transfer Ratio; MRI brain T1 hypointensity load; T cell response suppression; Multiple Sclerosis Functional Composite Score; Expanded Kurtzke Disability Status Score
Expected Total Enrollment: 20
Design: 1 year cross over, single treatment at 6 months
http://www.clinicaltrials.gov/ct/show/N ... 0?order=13
Another pre-clinical candidate.
Q Therapeutics Wins Biotechnology Innovation Award for 2007
May 21 2007 -- Business Wire -- Q Therapeutics, Inc. announced today that it has been awarded the 2007 Utah Innovation Award for Biotechnology/Pharmaceuticals. The award honors Q's development of Q-Cells(TM), a cell therapy product used to regenerate the myelin sheath on neurons that have lost their insulating myelin layer due to disease or injury. The innovation has applicability to a wide variety of diseases and injuries of the central nervous system including multiple sclerosis, white matter stroke, spinal cord injury, and other demyelinating diseases of the human central nervous system. Q has exclusively licensed the technology underlying the Q-Cells from the University of Utah. The award was conferred by the Utah Technology Council in collaboration with Stoel Rives, LLC.
"We are very pleased and honored to have our scientific team and their achievements recognized in this fashion," said Deborah Eppstein Ph.D., President and CEO of Q Therapeutics. "This award comes on the heels of years of scientific research and development in the labs of both Q Therapeutics and our scientific co-founder Mahendra S. Rao, M.D. Ph.D. We look forward to moving this work into the clinic and being able utilize it in the treatment of several debilitating diseases for which there currently are no restorative therapies."
According to Brian Cummings, Director of the University of Utah Technology Commercialization Office, "The Q-Cells technology holds the promise of a new standard in cell-based therapy. The University is very committed to seeing the work of its researcher's progress in the area of stem-cell research. The recognition of Q-Cells as the best Utah biotechnology innovation for 2007 confirms that our commitment to the development of cell-therapy technologies is well founded and it will continue."
Q Therapeutics is an emerging biopharmaceutical company, venture-backed and privately held, located in Salt Lake City, Utah. The Company is developing products to treat debilitating diseases of the central nervous system. The Company's first product, Q-Cells(TM), is a cell-based therapeutic intended to replace the insulating myelin on damaged neurons and thus regenerate normal function of these neurons. Q-Cells are applicable to a wide range of demyelinating diseases, including multiple sclerosis (MS), cerebral palsy, spinal cord injury and white matter stroke. Clinical trials are targeted to commence in 2008 in Transverse Myelitis, a rapidly paralyzing, inflammatory spinal cord injury related to MS. Q's pipeline includes other cell products for treating diseases including Parkinson's and Alzheimer's Diseases and ALS, as well as peripheral neuropathies. For more information contact Deborah Eppstein Ph.D., President & CEO, Q Therapeutics, Inc. at 801-582-5400.
http://www.genengnews.com/news/bnitem.a ... e=17788413
Q Therapeutics Wins Biotechnology Innovation Award for 2007
May 21 2007 -- Business Wire -- Q Therapeutics, Inc. announced today that it has been awarded the 2007 Utah Innovation Award for Biotechnology/Pharmaceuticals. The award honors Q's development of Q-Cells(TM), a cell therapy product used to regenerate the myelin sheath on neurons that have lost their insulating myelin layer due to disease or injury. The innovation has applicability to a wide variety of diseases and injuries of the central nervous system including multiple sclerosis, white matter stroke, spinal cord injury, and other demyelinating diseases of the human central nervous system. Q has exclusively licensed the technology underlying the Q-Cells from the University of Utah. The award was conferred by the Utah Technology Council in collaboration with Stoel Rives, LLC.
"We are very pleased and honored to have our scientific team and their achievements recognized in this fashion," said Deborah Eppstein Ph.D., President and CEO of Q Therapeutics. "This award comes on the heels of years of scientific research and development in the labs of both Q Therapeutics and our scientific co-founder Mahendra S. Rao, M.D. Ph.D. We look forward to moving this work into the clinic and being able utilize it in the treatment of several debilitating diseases for which there currently are no restorative therapies."
According to Brian Cummings, Director of the University of Utah Technology Commercialization Office, "The Q-Cells technology holds the promise of a new standard in cell-based therapy. The University is very committed to seeing the work of its researcher's progress in the area of stem-cell research. The recognition of Q-Cells as the best Utah biotechnology innovation for 2007 confirms that our commitment to the development of cell-therapy technologies is well founded and it will continue."
Q Therapeutics is an emerging biopharmaceutical company, venture-backed and privately held, located in Salt Lake City, Utah. The Company is developing products to treat debilitating diseases of the central nervous system. The Company's first product, Q-Cells(TM), is a cell-based therapeutic intended to replace the insulating myelin on damaged neurons and thus regenerate normal function of these neurons. Q-Cells are applicable to a wide range of demyelinating diseases, including multiple sclerosis (MS), cerebral palsy, spinal cord injury and white matter stroke. Clinical trials are targeted to commence in 2008 in Transverse Myelitis, a rapidly paralyzing, inflammatory spinal cord injury related to MS. Q's pipeline includes other cell products for treating diseases including Parkinson's and Alzheimer's Diseases and ALS, as well as peripheral neuropathies. For more information contact Deborah Eppstein Ph.D., President & CEO, Q Therapeutics, Inc. at 801-582-5400.
http://www.genengnews.com/news/bnitem.a ... e=17788413
Good news: another drug entering phase II for MS.
Genmab to start Phase III studies of HuMax-CD20 in rheumatoid arthritis
Thomson Financial - Genmab AS said it expects to initiate Phase III studies of ofatumumab (HuMax-CD20) in rheumatoid arthritis (RA) by the end of 2007.
HuMax-CD20 is is being developed under a worldwide co-development and commercialisation agreement between Genmab and GlaxoSmithKline.
Genmab said the group also plans to expand the development programme through a Phase II study in relapsing remitting multiple sclerosis (RRMS) in the first quarter of 2008.
There is potential to pursue indications in a wide range of autoimmune disease settings, Genmab said.
The Danish pharma group added the development plans for ofatumumab will be described at GSK's Oncology Seminar.
Ofatumumab is currently in late stage development for chronic lymphocytic leukemia (CLL), follicular non-Hodgkin's lymphoma (NHL) and in Phase II for RA.
Genmab said a clear demonstration of the efficacy and safety of ofatumuamb in two late stage trials for CLL and follicular NHL could provide the initial regulatory applications.
The company has received a Fast Track designation for the CLL study.
Under these circumstances, it said, 'ofatumumab could potentially enter the market in 2008 first for the treatment of refractory CLL and subsequently for rituximab-refractory follicular NHL.'
The group has planned initiation of clinical studies for ofatumumab in diffuse large B-cell lymphoma (DLBCL) by the end of 2007 and randomised
Phase III studies in CLL and follicular NHL in the first half of 2008.
http://www.forbes.com/markets/feeds/afx ... 30135.html
Genmab to start Phase III studies of HuMax-CD20 in rheumatoid arthritis
Thomson Financial - Genmab AS said it expects to initiate Phase III studies of ofatumumab (HuMax-CD20) in rheumatoid arthritis (RA) by the end of 2007.
HuMax-CD20 is is being developed under a worldwide co-development and commercialisation agreement between Genmab and GlaxoSmithKline.
Genmab said the group also plans to expand the development programme through a Phase II study in relapsing remitting multiple sclerosis (RRMS) in the first quarter of 2008.
There is potential to pursue indications in a wide range of autoimmune disease settings, Genmab said.
The Danish pharma group added the development plans for ofatumumab will be described at GSK's Oncology Seminar.
Ofatumumab is currently in late stage development for chronic lymphocytic leukemia (CLL), follicular non-Hodgkin's lymphoma (NHL) and in Phase II for RA.
Genmab said a clear demonstration of the efficacy and safety of ofatumuamb in two late stage trials for CLL and follicular NHL could provide the initial regulatory applications.
The company has received a Fast Track designation for the CLL study.
Under these circumstances, it said, 'ofatumumab could potentially enter the market in 2008 first for the treatment of refractory CLL and subsequently for rituximab-refractory follicular NHL.'
The group has planned initiation of clinical studies for ofatumumab in diffuse large B-cell lymphoma (DLBCL) by the end of 2007 and randomised
Phase III studies in CLL and follicular NHL in the first half of 2008.
http://www.forbes.com/markets/feeds/afx ... 30135.html
Based on the information below, I'm going to assume that the DNA vaccination developed by Steinman at Stanford is actually now BHT-3009.
Bayhill Therapeutics Inc., founded with technology developed in Professor Lawrence Steinman's laboratory at Stanford University, is focused on the translation of research into therapeutics by developing novel drugs for the treatment of autoimmune diseases. The company has established a therapeutic platform of BHT-DNA(TM) antigen-specific therapeutics, with broad potential applications in treating autoimmune diseases, including multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. Bayhill's lead product in this platform, BHT-3009, is an antigen-specific DNA plasmid and is currently in early-stage clinical testing in multiple sclerosis patients. Bayhill is preparing for a phase II trial to begin in early 2006.
I'm removing flecainide from the phase II section. It's in there (I think) because of this bit:
Dr. Kapoor is now overseeing the lamotrigine trial, so when they say that a clinical trial was to start in 2005 based on those flecainide results, I believe they decided to go with lamotrigine instead of (not in addition to) flecainide.
Somebody stop me if you know better.
But then further down the same page, I noticed this:Patients with multiple sclerosis can experience permanent loss of function due to the degeneration of large numbers of nerve fibres. No current therapy is known to protect fibres, but this research indicates that sodium channel blocking drugs can be effective. Upper photographs show cross-sections through the spinal cord in which nerve fibres have been labelled brown. On the left can be seen a pale area in which nearly all nerve fibres have degenerated (shown at high magnification below) due to the disease process. On the right, nearly all the nerve fibres have been protected by therapy with a flecainide sodium channel blocking agent, despite the presence of the disease. The graph indicates that nearly all the nerve fibres (or axons) have been protected. A clinical trial in multiple sclerosis will start during 2005, based on these observations.
http://www.kcl.ac.uk/depsta/medicine/de ... ual02.htmlBechtold D, Kapoor R, Smith KJ. Axonal protection using flecainide in experimental autoimmune encephalomyelitis. Ann Neurol 2004;55:607-616.
Dr. Kapoor is now overseeing the lamotrigine trial, so when they say that a clinical trial was to start in 2005 based on those flecainide results, I believe they decided to go with lamotrigine instead of (not in addition to) flecainide.
Somebody stop me if you know better.
Another new one for phase I, I'll call it a "Nogo-A blocker". Technically it's for spinal cord injury/stroke, so I'm not sure if I should add it...anyway, I think they'll end up naming it something like "nogozamex"...unless they can figure out how to squeeze more x's in there. Can't have too many x's in a drug name.
New strategies to treat neurological disorders
20/06/2007 - Experts from around the world have gathered this week to discuss the best emerging therapies for a number of neurological disorders such as multiple sclerosis and stroke.
Thousands of scientists and clinicians have descended on the island of Rhodes, Greece for the European Neurological Society (ENS) congress and the latest drugs are the centre of attention.
One central topic at the scientific conference is multiple sclerosis (MS), a chronic inflammatory disease that attacks the central nervous system (CNS).
"About 400,000 people in Europe have MS and about one million worldwide," said the ENS president, Professor Giancarlo Comi.
"MS is still not curable. A number of new findings have been made in recent years, however, with regard to the origins of the disease and new therapeutic strategies. These new insights help us to mitigate the course of the disease and delay the development of permanent disabilities."
The scientists took time to focus on the mechanisms underlying the process of axonal degeneration which characterise the progressive phase of the disease. There is some evidence that some of these mechanisms are at least partially independent from inflammation.
According to Prof. Comi, modulating and suppressing the immune system only has a modest effect at best on the progressive phase of the disease.
"One important goal in the treatment of this severe disease has to be to develop therapies that repair the damage MS causes in nerve cells," Professor Comi said. "There is increasing scientific evidence that the course of MS is shaped by different disease mechanisms in its early and late phase."
Researchers from France, Germany and Switzerland believe they have proof for a hypothesis first posited in the late 19th century. According to this new evidence, certain stem cells differentiate very early on in human development into nerve cells or into glia cells - the maintenance and support cells in the CNS.
They showed that there are two different types of stem cells that differentiate into either glia or nerve cells. This finding from Dr Zalc, Hôpital Pitié Salpêtrière, Paris, and colleagues, contradicts the viewpoint that nerve cells form first and that glia cells then develop from them.
Prof. Comi said: "Key fundamental research findings like these could well enable MS therapy to advance in significant ways."
Professor Martin Schwab, from the University of Zurich, presented promising results for his antibody therapy that can restimulate nerve growth in animals, following injury or stroke. In the human brain, nerve fibre growth is restricted to distances below 2mm as it is inhibited by several substances found in myelin sheaths - the protective coverings found on nerves.
One of these substances is the membrane protein Nogo-A. Prof. Schwab and his team have developed an antibody that blocks this target. When they tested its effect in animals, they found that the drug stimulated nerve fibre growth over comparatively long distances substantially improved "functional restoration", such as running, swimming or gripping.
Professor Ioannis Milonas, chairman of the ENS Congress, said: "The new agent is currently being tested in a Phase I clinical study in a European network of centres for spinal cord injuries."
URL
New strategies to treat neurological disorders
20/06/2007 - Experts from around the world have gathered this week to discuss the best emerging therapies for a number of neurological disorders such as multiple sclerosis and stroke.
Thousands of scientists and clinicians have descended on the island of Rhodes, Greece for the European Neurological Society (ENS) congress and the latest drugs are the centre of attention.
One central topic at the scientific conference is multiple sclerosis (MS), a chronic inflammatory disease that attacks the central nervous system (CNS).
"About 400,000 people in Europe have MS and about one million worldwide," said the ENS president, Professor Giancarlo Comi.
"MS is still not curable. A number of new findings have been made in recent years, however, with regard to the origins of the disease and new therapeutic strategies. These new insights help us to mitigate the course of the disease and delay the development of permanent disabilities."
The scientists took time to focus on the mechanisms underlying the process of axonal degeneration which characterise the progressive phase of the disease. There is some evidence that some of these mechanisms are at least partially independent from inflammation.
According to Prof. Comi, modulating and suppressing the immune system only has a modest effect at best on the progressive phase of the disease.
"One important goal in the treatment of this severe disease has to be to develop therapies that repair the damage MS causes in nerve cells," Professor Comi said. "There is increasing scientific evidence that the course of MS is shaped by different disease mechanisms in its early and late phase."
Researchers from France, Germany and Switzerland believe they have proof for a hypothesis first posited in the late 19th century. According to this new evidence, certain stem cells differentiate very early on in human development into nerve cells or into glia cells - the maintenance and support cells in the CNS.
They showed that there are two different types of stem cells that differentiate into either glia or nerve cells. This finding from Dr Zalc, Hôpital Pitié Salpêtrière, Paris, and colleagues, contradicts the viewpoint that nerve cells form first and that glia cells then develop from them.
Prof. Comi said: "Key fundamental research findings like these could well enable MS therapy to advance in significant ways."
Professor Martin Schwab, from the University of Zurich, presented promising results for his antibody therapy that can restimulate nerve growth in animals, following injury or stroke. In the human brain, nerve fibre growth is restricted to distances below 2mm as it is inhibited by several substances found in myelin sheaths - the protective coverings found on nerves.
One of these substances is the membrane protein Nogo-A. Prof. Schwab and his team have developed an antibody that blocks this target. When they tested its effect in animals, they found that the drug stimulated nerve fibre growth over comparatively long distances substantially improved "functional restoration", such as running, swimming or gripping.
Professor Ioannis Milonas, chairman of the ENS Congress, said: "The new agent is currently being tested in a Phase I clinical study in a European network of centres for spinal cord injuries."
URL
I've been looking for signs of life from Transition Therapeutics' interferon enhancing therapy. The trail runs cold in September 2006. At the time, they said they were looking for a partner to help them move their phase II trial along. Since then, there has been no mention of it. While this link to their website still works:
http://www.transitiontherapeutics.com/technology/ms.php
you can't get to it by navigating the site. It looks like they just haven't covered their tracks very carefully. I assume they are doing the usual corporate sweeping failure under the rug routine. Sort of a sub-par performance though, I can't possibly give them anything higher than a C+.
Another one bites the dust.
http://www.transitiontherapeutics.com/technology/ms.php
you can't get to it by navigating the site. It looks like they just haven't covered their tracks very carefully. I assume they are doing the usual corporate sweeping failure under the rug routine. Sort of a sub-par performance though, I can't possibly give them anything higher than a C+.
Another one bites the dust.
Sorry, more bloodshed to report. Merck's website contains no mention of L-000124467 (phase 2). The trial was due to finish in March 2007.
Merck Pipeline
Merck Pipeline
Well, they don't make it easy to learn about their failures, but at least there is a reference to former phase 2 candidate TV 5010 from Teva, may it rest in peace:
TV 5010 for MS
The efficacy and safety of once-weekly subcutaneous injections of TV-5010, a high molecular-weight copolymer comprised of the same four amino acids present in glatiramer acetate, was examined in two Phase II trials. This project was terminated at the end of 2006.
http://www.tevapharm.com/pdf/20f06_isa.pdf
TV 5010 for MS
The efficacy and safety of once-weekly subcutaneous injections of TV-5010, a high molecular-weight copolymer comprised of the same four amino acids present in glatiramer acetate, was examined in two Phase II trials. This project was terminated at the end of 2006.
http://www.tevapharm.com/pdf/20f06_isa.pdf
Thanks Carole.
Here's one that's going backwards. Celera Genomics announced that CRA-028129 was in a phase 1 trial, but it has been purchased by Schering. I guess there is a connection between Bayer and Schering, and in a 20-F SEC report this year, Bayer had this to say about CRA-028129 (phooey):
In June 2006, we acquired Celera Genomic's cathepsin S inhibitor drug
development program. These oral cathepsin S inhibitors are small molecules with an innovative mode-of-action that have potential in the treatment of auto-immune diseases like multiple sclerosis, Crohn's, psoriasis and rheumatoid arthritis. We have exclusive rights worldwide. The technology is still in a pre-clinical stage.
http://sec.edgar-online.com/2007/03/15/ ... ction1.asp
Here's one that's going backwards. Celera Genomics announced that CRA-028129 was in a phase 1 trial, but it has been purchased by Schering. I guess there is a connection between Bayer and Schering, and in a 20-F SEC report this year, Bayer had this to say about CRA-028129 (phooey):
In June 2006, we acquired Celera Genomic's cathepsin S inhibitor drug
development program. These oral cathepsin S inhibitors are small molecules with an innovative mode-of-action that have potential in the treatment of auto-immune diseases like multiple sclerosis, Crohn's, psoriasis and rheumatoid arthritis. We have exclusive rights worldwide. The technology is still in a pre-clinical stage.
http://sec.edgar-online.com/2007/03/15/ ... ction1.asp
DW-908e from the phase 1 section is gone. No sign of it on Daiichi's website. Could somebody please just get a couple of these damn drugs approved already?! I'm getting sick of this failure business.
http://www.daiichisankyo.com/ir/rd/index.html
http://www.daiichisankyo.com/ir/rd/index.html