Long Time, No Post

Sorry for the recent delay in posting.  I hope everyone had a Happy Thanksgiving!  My whole family got together which was great!  I have kept very busy lately, so I haven't had many chances to get on here to post.  Also, our computer got a virus, so we had to fix that before I could post.

And now, some news from the NMSS website:

The company Opexa Therapeutics (The Woodlands, TX) announced that the experimental therapy Tovaxin® has been designated by the U.S. Food and Drug Administration as a “Fast Track Product” for the treatment of secondary-progressive MS. Tovaxin is a personalized vaccine that aims to induce immunity against T cells that attack the brain and spinal cord in MS. It uses a person’s own immune cells, which are removed, manipulated, and then reintroduced by under the skin injections. The Fast Track designation may expedite its future review by the FDA after the company submits results of future phase III trials. The company is planning to begin a Phase IIb clinical trial of Tovaxin in secondary-progressive MS “subject to securing the necessary resources,” according to a November 8, 2011 press release.
Results so far: A one-year, multi-center trial of Tovaxin was conducted in 140 people with relapsing-remitting MS and 10 people who had experienced a neurological episode that put them at possible risk for being diagnosed with MS. The TERMS study found Tovaxin to be safe, but did not achieve statistical significance in the primary endpoint evaluating the cumulative number of active MRI lesions in those on active therapy versus those on placebo (Multiple Sclerosis, published online November 6). Analyzing a subset of participants after the study, investigators found that Tovaxin stabilized or reduced disability as measured by the EDSS scale, and the average number of relapses in a year.
Tovaxin is a trademark of Opexa Pharmaceutics.

This is VERY exciting because its focus is secondary-progressive MS rather than relapsing-remitting, which is what most therapies treat. Another article off of the NMSS website:

Genzyme has announced that the experimental intravenous therapy alemtuzumab (with a proposed brand name Lemtrada™) met two primary endpoints by significantly reducing relapse rates and the worsening of disability in a two-year study comparing alemtuzumab to standard subcutaneous dosing of Rebif® (interferon beta-1a, EMD Serono Inc. and Pfizer). The study, called CARE-MS II, involved 840 people with relapsing-remitting MS. The results were announced in a November 14, 2011 press release, which also indicated that the company plans to apply in early 2012 to the U.S. Food and Drug Administration for marketing approval. Data analysis is ongoing and the company expects to provide a full report at an upcoming medical meeting. Alemtuzumab has been designated by the FDA as a “Fast Track Product,” which should expedite its future review.
Background: MS involves immune system attacks against brain and spinal cord tissues. Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) that is currently approved for the treatment of B-cell chronic lymphocytic leukemia. Its ability to target immune cells led investigators to test its potential as a treatment for relapsing-remitting MS. In an earlier phase II study comparing two dose levels of alemtuzumab with Rebif in 334 subjects with relapsing-remitting MS, those taking alemtuzumab had a 74% reduction in the risk of MS relapse compared with those on Rebif, and a 71% reduction in the risk for sustained worsening of disability (New England Journal of Medicine 2008 359;17:30-45).
Dosing was temporarily suspended in the Phase II study due to the occurrence of immune thrombocytopenic purpura (ITP), a rare condition in which low blood platelet counts can lead to abnormal bleeding. After the first cases of ITP occurred, one of which was fatal, Genzyme implemented a patient safety monitoring program which includes patient and physician education and regular contacts with patients.
Investigators recently reported on another phase III trial of alemtuzumab. The two-year CARE-MS-I phase III trial compared alemtuzumab against Rebif in 581 people with early relapsing-remitting MS. The study met one of two primary endpoints by reducing relapse rates by 55% over Rebif, but did not meet its second primary endpoint of slowing disease progression compared to Rebif. (Abstract #151, ECTRIMS 2011)
This Study: In the CARE-MS II study, 840 people with relapsing-remitting MS, who had experienced relapse while on a prior therapy, were randomly assigned to receive alemtuzumab or Rebif. Alemtuzumab was given by intravenous infusion for 5 days initially and for 3 days one year later. Those on Rebif received the standard dose of 3-times weekly subcutaneous injections. According to the company press release, after two years the relapse rate of those on alemtuzumab was reduced by 49% compared to those on Rebif, and the risk of sustained worsening of disability (as measured by the EDSS scale) was reduced by 42% compared to Rebif. (These were the primary endpoints of the study.)
According to the press release, approximately 16% of those treated with alemtuzumab developed autoimmune thyroid-related problems and approximately 1% developed ITP. All cases were detected early through a monitoring program and managed with conventional therapies. Other common adverse events associated with alemtuzumab included reactions associated with infusions (such as headache, rash, fever, flushing, hives and chills). The most common infections in those treated with alemtuzumab (all mild to moderate) were upper respiratory and urinary tract infections, sinusitis and herpes simplex infections.
Comment: The completion of this second Phase III trial of alemtuzumab is a milestone that paves the way for the company to apply to the FDA for marketing approval. Full details and evaluation of this study should help define the safety and promise of alemtuzumab as a potential new therapy for relapsing MS.

Love the ongoing research; I remain optimistic that a cure will come in my lifetime!  So many advances have been made in just the past decade alone!

A Little Bit of This, A Little Bit of That

Random excerpts from my MSIF e-mailers:

A good reason to find a doctor that you like: An "study from Italy found that a good physician-patient relationship improves both patient satisfaction and adherence to long-term therapy."

A randomized trial of new drug, Simvastatin, "involved giving 80 mg Simvastatin daily for six months to people with optic neuritis. The results suggest that this is well tolerated and possibly effective in patients with acute optic neuritis."

"Alemtuzumab, a candidate treatment for MS, has the potential side effect of autoimmune disease. In this study, the authors analyse both clinical and serological data of patients with MS treated with alemtuzumab. It was found that autoimmune disease developed in 22.2% of those treated with a range of different systems affected."



And now, from the NMSS website, What Causes MS in Kids?:

Investigators nationwide are recruiting 640 children with early relapsing-remitting MS or CIS (clinically isolated syndrome, a single episode of MS-like symptoms) and 1280 children without MS or CIS for a four-year study to determine environmental and genetic risk factors that make children susceptible to developing MS. The study, funded by the National Institutes of Health, leverages the National MS Society’s support of the Promise:2010 Pediatric Network of Centers of Excellence.
Background: This study takes advantage of the collaborative efforts of the Pediatric Network. Although the initial grants end this year, there is funding through 2012 to support a data coordination and analysis center so the Network can continue to collect data and study pediatric MS and related disorders. The Network produced over 150 papers, posters and presentations on pediatric MS and network members are the lead authors and editors of a textbook on Pediatric MS from Cambridge Press.
The five-year, $3.2 million grant to lead investigator Dr. Emmanuelle Waubant (University of California, San Francisco Pediatric MS Center) from the NIH is based on pilot data collected by the Network in a study of 180 children with MS. That study confirmed previous reports that the Epstein-Barr virus (which causes infectious mononucleosis and other disorders) was associated with higher risk of MS. They also reported that cytomegalovirus was associated with a lower risk of developing MS, and that herpes simplex virus type 1was associated with increased risk in children who did not have a specific immune-related gene. (Neurology 2011;76:1989–1995)
These findings and other factors are being investigated further in the new study, which should help us understand more about how MS begins in children and can eventually be applied to adult forms of MS. Read more about what triggers MS.
The Study: Those under age 18 who had disease onset (MS or CIS) in the last two years may enroll in this study with the consent of their parents. Children without MS or CIS can enroll if they are 19 or younger and don’t have a demyelinating disease or an autoimmune disorder (except asthma).
Participants are providing blood samples to test for genetic and environmental risk factors that may be associated with pediatric MS. Next, all participants are completing questionnaires about relevant environmental factors. Investigators also will draw information from participants’ medical records.
Investigators specifically are looking at genes, Epstein Barr and other common viruses, vitamin D levels, and exposure to cigarette smoking. They are attempting to confirm these risk factors separately and to determine whether there are any interactions between them.

It would be great to have more answers!

Phase III Trial Results (Alemtuzumab & Laquinimod)

From the NMSS's website, the results of Phase III trials:

First, Alemtuzumab:

Sanofi and its subsidiary Genzyme have announced that the experimental intravenous therapy alemtuzumab (with a proposed brand name Lemtrada,™) met one of two primary endpoints by significantly reducing relapse rates in a two-year study comparing two annual cycles of alemtuzumab against standard subcutaneous dosing of Rebif^® (interferon beta-1a, EMD Serono Inc. and Pfizer). The study, called CARE-MS I, involved 581 people with early relapsing-remitting MS. The study did not meet its second primary endpoint of slowing disease progression compared to Rebif. The results were announced in July 11 press release. Data analysis is ongoing and the company expects to provide a full report at an upcoming medical meeting. Another trial of alemtuzumab, called CARE-MS-II, is currently underway.
Background: Multiple sclerosis involves immune system attacks against brain and spinal cord tissues. Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) that is currently approved by the U.S. FDA for the treatment of B-cell chronic lymphocytic leukemia. Its ability to target immune cells led investigators to test its potential as a treatment for relapsing-remitting MS. An earlier phase II study compared two dose levels of alemtuzumab with Rebif in 334 subjects with relapsing-remitting MS who had never taken any other disease-modifying therapies. Those taking alemtuzumab had a 74% reduction in the risk of MS relapse compared with those on Rebif, and a 71% reduction in the risk for sustained accumulation of disability (New England Journal of Medicine 2008 359;17: 30-45).
Dosing was temporarily suspended in the Phase II study due to the occurrence of immune thrombocytopenic purpura (ITP), a rare condition in which low blood platelet counts can lead to abnormal bleeding. After the first cases of ITP occurred, one of which was fatal, Genzyme implemented a patient safety monitoring program which includes patient and physician education and regular contacts with patients. Two phase III studies comparing alemtuzumab with Rebif were then launched.
In June 2010, it was announced that alemtuzumab had been designated by the FDA as a “Fast Track Product.” This designation should expedite its future review by the FDA after the company submits results of the phase III trials. The press release stated that the company expects to file for regulatory approval of alemtuzumab for MS in early 2012.
This Study: In the CARE-MS I study, approximately 581 people with early, active relapsing-remitting MS, who had never received disease-modifying therapy to treat their MS, were randomly assigned to receive alemtuzumab or Rebif. Alemtuzumab was given by intravenous infusion for 5 days initially and for 3 days one year later. Those on Rebif received the standard dose of 3-times weekly subcutaneous injections. According to the press release, after two years the relapse rate of those on alemtuzumab was reduced by 55 percent compared to those on Rebif. After two years, 8 percent of those on alemtuzumab had an increase in their EDSS score (a standard scale of physical disability) compared to 11 percent on Rebif – a difference that was not statistically significant.
According to the press release, the most common adverse event associated with alemtuzumab in the CARE-MS I study included reactions associated with infusions (such as headache, rash, fever, flushing, hives and chills). There were more infections in those taking alemtuzumab, predominantly mild to moderate, and there were no fatal infections. Less than 20 percent on alemtuzumab developed autoimmune thyroid-related problems and less than one percent developed ITP.
In the ongoing CARE-MS II study, approximately 1200 subjects at over 250 study sites have been randomly assigned to receive one of two alemtuzumab treatment regimens, or Rebif.
Comment: These positive results are the first reported from this Phase III study of alemtuzumab. Full details and evaluation of this study, and from another Phase III study now underway, should help define the safety and promise of alemtuzumab as a potential new therapy for relapsing MS.

Next,  Laquinimod:

Teva Pharmaceutical Industries Ltd. and Active Biotech announced in a press release that the phase III BRAVO study, in which the experimental oral drug laquinimod was tested against inactive placebo in a study involving over 1300 people with relapsing-remitting MS, did not reach its primary goal of reducing the average number of relapses in a year. However, when the investigators adjusted the data to correct for differences in magnetic resonance imaging characteristics at the start of the study, a significant reduction in average annual relapse rate was observed in the group receiving the laquinimod. Further analysis is ongoing, and the results are being submitted for presentation at a scientific meeting later this year. The companies state that they plan to submit applications to regulatory authorities for the treatment of MS in the United States and European Union.
Background: Multiple sclerosis occurs when the immune system mistakenly attacks nerve fiber-insulating myelin and other brain and spinal cord tissues. Laquinimod is a monoclonal antibody believed to affect the immune attack. In an earlier phase II study involving 306 people with relapsing-remitting MS, oral laquinimod reduced disease activity by 40.4% compared with inactive placebo. (Lancet 2008; 371: 2085–92) In one phase III study – the ALLEGRO study – laquinimod reduced the annual relapse rate in those completing the trial by 23%, compared to those on placebo. (Late-Breaking News – American Academy of Neurology, 2011)
The Study: In the BRAVO study, participants were randomly assigned to receive either laquinimod 0.6 mg (one capsule daily), inactive placebo, or Avonex® (interferon beta-1a, Biogen Idec) 30 mcg/wk for 24 months. The primary goal of the study was to determine the effect of laquinimod on the rate of relapses. Secondary goals included impacts on disease activity as observed on MRI scans, and accumulation of disability. Laquinimod was not directly compared to Avonex, but just to the inactive placebo.
Laquinimod did not reduce the annualized relapse rate significantly more than placebo. According to the press release, there were differences in MRI characteristics between the treatment groups at the beginning of the study, and when the data were adjusted to account for these differences, laquinimod was found to reduce annualized relapse rate, disability progression (as measured by the EDSS scale of disease activity), and brain tissue volume loss significantly more than placebo. No details were released related to safety, except to state that “laquinimod demonstrated a favorable safety and tolerability profile compared to placebo.”
According to the companies, further analysis is ongoing, and the results are being submitted for presentation at a scientific meeting later in the year. The companies plan to submit applications to regulatory authorities for the treatment of MS in the United States and European Union. The complete data from the BRAVO and ALLEGRO studies should help define the safety and promise of laquinimod as a potential new oral therapy for relapsing-remitting MS.

Always nice to know what progress is being made!