By Charles Craig
SAN FRANCISCO * As Biogen Inc., Berlex Laboratories Inc. and Teva Pharmaceuticals Inc. fight for dominance of the multiple sclerosis market, Connective Therapeutics Inc. is steadily progressing with a new approach to the debilitating degenerative disease.
Thomas Wiggans, president and CEO of Connective Therapeutics, said Thursday his Palo Alto, Calif.-based company began a Phase I/II study of a T cell receptor vaccine in 100 multiple sclerosis patients.
Connective's approach to treating the autoimmune disease involves correcting the immune system imbalance believed to be responsible for multiple sclerosis.
Research has suggested the disorder is caused by what Wiggens calls "confused T cells," which destroy the myelin sheath protecting the central nervous system's nerve fibers. The result is a disruption of signals from the brain to the body, affecting numerous activities, such as movement, vision, speech, and short-term memory.
Research also has shown those bad T cells have a common surface receptor, which does not work properly. If it did, the immune system would be alerted to the errant T cells and respond to hold them in check.
Wiggens said Connective Therapeutics' peptide vaccine contains a 20-amino acid segment from the targeted T cell receptor. When administered to multiple sclerosis patients the vaccine is designed to trigger the immune system response to correct the imbalance, halting the T cell attack on the myelin sheath.
Wiggans discussed the multiple sclerosis therapeutic vaccine at the Hambrecht & Quist 15th Annual Healthcare Conference here. The four-day meeting ended Thursday.
Connective Therapeutics' Phase I/II study will attempt to duplicate successful results from a smaller, 23-patient trial conducted by the company's partner, the Veterans Affairs Medical Center at the Oregon Health Sciences University in Portland. (See BioWorld Today, Oct. 2, 1996, p. 1.)
In that study, six of the multiple sclerosis patients who experienced an immune system response to the peptide vaccine showed clinical improvement or achieved stabilization of their condition.
The primary endpoint in the Connective Therapeutics trial, Wiggans said, "will be to detect whether we have selectively raised the body's impact on the bad T cells."
If successful, the therapeutic vaccine could treat all multiple sclerosis patients, those with steadily progressive disease as well as those with relapsing and remitting forms of the disorder.
"We have reason to suspect that this kind of vaccine would halt the course of the disease if you can rebalance the immune system," Wiggans said.
Biogen, of Cambridge, Mass., sells Avonex for multiple sclerosis and Berlex, the Wayne, N.J.-based subsidiary of Schering AG, of Berlin, markets Betaseron, which is made by Chiron Corp., of Emeryville, Calif.
Avonex and Betaseron are interferon beta drugs approved by the FDA for reducing the flare-ups that occur in relapsing-remitting multiple sclerosis patients. Those patients account for about 50 percent of the 250,000 people afflicted with the disease in the U.S.
Teva, of Jerusalem, received FDA approval in December 1996 for Copaxone, a polypeptide of four amino acids from myelin basic protein. The drug is thought to suppress the immune system assault on the myelin sheath. But it also is approved only for relapsing-remitting multiple sclerosis patients.
Some analysts have speculated a combination of Copaxone and one of the interferon beta drugs may become a favored therapy.
As in other complex diseases, such as AIDS, multiple sclerosis, Wiggans said, eventually may be treated with a combination of drugs as more products with different mechanisms of action become commercially available. *