Future Therapies: The Finale (Tovaxin & Apitope Vaccines)

Tovaxin, by Opexa Therapeutics, is a cellular immunotherapy that has completed a Phase IIb clinical study for the treatment of MS.  It is a personalized T-cell vaccine for the treatment of multiple sclerosis (MS) that is specifically tailored to each patient's disease profile and is designed to reduce the number of specific subsets of autoreactive T-cells known to attack myelin.  It helps limit attacks by T-cells on myelin, the protein sheath that protects nerves.

Excerpts From Opexa Therapeutics' website:

Tovaxin is being developed as a first line treatment for MS. The treatment will consist of donating blood and creating a vaccine using the patient’s own cells. The vaccine cells will be irradiated to render them unable to divide, but able to evoke an immune response. The vaccines will be administered in the doctor’s office as a subcutaneous injection in the arm given five times a year. The first four injections are administered a month apart with the fifth and final injection being administered two months after the fourth. While many other MS treatments have constant side effects such as flu symptoms, injection site problems, and serious adverse events, Tovaxin has not had any treatment related serious adverse events (SAEs). The most common side effect reported form clinical studies has been mild to moderate injection site reaction that usually resolves without treatment within 24 hours. Tovaxin therapy is specific for the immune response against myelin destroying T cells and does not cause a general immunosuppression. Tovaxin may be a strong alternative for subjects who do not want to start hospital infusions or weekly injections, or have not been able to tolerate the side effects or infections of immunosuppressant drugs on the market.
Tovaxin treatment selectively targets and depletes the pathogenic T-cell population. It is not a general immune suppressant and accordingly, is not associated with the serious side effects seen by those MS treatments that function by systemically suppressing the immune system. In clinical trials conducted to date, including the 150-patient Phase 2b study, there have been no serious adverse events associated with Tovaxin treatment.
Phase IIb results:  Data from the 12-month analysis of the Phase IIb TERMS study demonstrated a number of positive outcomes. Recently announced data in patients with at least one relapse in the 12 months prior to study entry showed:

1. More than 83% of Tovaxin-treated patients remained relapse free at one year
2. 42% decrease in annual relapse rate (ARR) following treatment compared to placebo
3. 73% of Tovaxin-treated patients showed stabilization or improvement in MS disability including 16.5% with a sustained improvement in the Expanded Disability Status Scale (EDSS) of at least one full point.

All analyses of the TERMS study data have shown Tovaxin to be safe and well tolerated with no serious adverse events related to Tovaxin treatment. Mild injection site reaction was the most common adverse event.

This about.com article helps to better explain the process in layman's terms.  From the article:

MS is caused when certain immune cells attack the myelin in the central nervous system. These immune cells are called myelin-reactive T-cells (MRTCs). Everyone has them, but in people with MS, they become “active” and “pathogenic” (which simply means they are causing disease). No one knows why they “turn on” in this way in certain people – it is probably a combination of factors, including genetics, infections, vitamin D exposure and metabolism, etc. The fact remains that when these MRTCs get going, they cause MS. That means that the ideal way to treat MS would be to stop these MRTCs from doing their bad work.
Tovaxin is an attempt to do more than stop these MRTCs – it actually is designed to eliminate the exact T-cells that are doing the damage from our bodies, without affecting the rest of the immune system. How does it do this?
1) First, the Vaccine is Manufactured
The vaccine is made from each person’s MRTCs. That’s right – blood is taken from each person with MS, the MRTCs are isolated, multiplied to large quantities and attenuated (which means they are weakened so as not to pose a threat).
2) Next, It is Injected Into the Patient
The vaccine, containing 30 to 45 million of these attenuated MRTCs is put back into the patient, using a simple subcutaneous injection.
3) The Body Responds
The body recognizes these MRTCs as invaders, both because they are damaged and because there are so many of them. The immune system attacks these MRTCs, but more importantly, it attacks all of the circulating MRTCs (the ones that are still alive doing damage). Ultimately the MRTCs are eliminated by other T-cells. These T-cells are produced by memory white blood cells (memory WBCs), which will keep producing them as long as any MRTCs are detected.
This has two effects: 1) Controls and gets rid of MRTCs, and 2) Rebalances the whole immune system so that it is no longer in “inflammation” mode. The second point is important, because in a person with relapsing forms of MS, it is not just MRTCs that cause damage – an army of other immune cells that are signaled by the activity of the MRTCs also contribute to the creation of lesions, which in turn cause the symptoms of MS.

Opexa has met with the FDA and hopes to begin Phase III trials very soon.  Sounds like the vaccine approach could work and be a very viable option in the future!



From an Apitope news release:

Apitope, the European biotech company developing therapeutic peptides to treat autoimmune and allergic diseases, announced the start of its second Phase I clinical trial of ATX-MS-1467, in patients with Multiple Sclerosis (MS).

ATX-MS-1467, an investigational peptide-based therapeutic derived from Apitope’s proprietary technology platform, has already completed successfully a Phase I clinical trial in six patients with secondary progressive MS (SPMS). This new Phase I study aims to build on the results from the initial study and investigates safety and proof-of-principle of ATX-MS-1467 in 40 patients with relapsing forms of MS (RMS).

Apitope is developing ATX-MS-1467 with Merck Serono, one of the leading pharmaceutical companies in the treatment of MS. Under the terms of the agreement between the two companies, Apitope is responsible for all Phase I development of ATX-MS-1467. Merck Serono will take over development of the compound at the beginning of Phase II clinical trials.
ATX-MS-1467 consists of four synthetic peptides that mimic naturally occurring peptides derived from human Myelin Basic Protein (MBP), a key autoantigen in multiple sclerosis. ATX-MS-1467 has been designed from naturally occurring MBP fragments and is intended to selectively inhibit the immune system's harmful attack on the protective myelin sheath surrounding the nervous cells while preserving the normal immune response to any harmful antigens, such as infections.

 
Unfortunately, there was not a whole lot of information available about ATX-MS-1467 because it is still so early on in clinical trials, but I look forward to hearing more about it and sharing that information with you.
This post wraps up the "Future Therapies" portion of the Teleconference information.


In other news, a fellow MSer, who has been blogging about his experiences and knowledge of therapies for some time had a great post recently.  He had the CCSVI procedure and has blogged a number of times about CCSVI.  His recent post primarily discusses the views and ongoing debates regarding CCSVI.  If you'd like to read his post, click here.

Also, I recently became a member of WEGO Health, a website for "health activists."  I am very excited to be a member of many of the groups, including the Multiple Sclerosis group!