After the Phase 2b clinical trial named Abili-T achieved full enrollment with 190 secondary progress multiple sclerosis (SPMS) patients, The Woodlands, Texas-based Opexa Therapeutics is patiently awaiting results for the company’s lead candidate, Tcelna, which are expected in the second half of 2016. The therapy, which was spun off from a technology developed at Baylor College of Medicine (BCM) Technologies that was licensed and developed by Opexa, has shown efficacy in both SPMS and relapsing-remitting multiple sclerosis (RRMS) patients in earlier clinical trials.
“We have spent a good decade in clinical trials treating early- and late-stage multiple sclerosis,” said Neil Warma, President and CEO of Opexa Therapeutics, in an exclusive interview with Multiple Sclerosis News Today. “In true fashion, we are trying to restore function of the immune system via personalized therapies that fight the root cause of disease itself.”
The focus of Tcelna is the interaction between T-cells and the rest of the body. “It is similar in concept to a T-cell vaccine, but these ‘vaccines’ are personalized for patients with multiple sclerosis,” explained Warma. “In patients with multiple sclerosis, there is a small population of myelin reactive T-cells (MRTCs) that cross into the central nervous system and attack nerve fibers. We isolate and identify those pathogenic T-cells, attenuate them, and reintroduce them back into the individual.”
First, a sample of blood is taken from a patient and sent to Opexa’s Good Manufacturing Practices (GMP) facility in Houston. Scientists then identify the specific myelin peptide antigens that the patient’s MRTCs recognize. Out of 109 peptides screened by Opexa, typically three or four peptides are dominant, and are introduced to a population of expanding T-cells. After a few more manufacturing steps to attenuate the reactive T-cells, these are then shipped to the patient’s physician’s office, who receives a subcutaneous injection of the “T-cell vaccine.”
“The injection primes the body to selectively recognize and attack the MRTCs,” said Warma. “It’s telling the immune system that these attenuated cells should be treated as foreign attackers.” Although the injection delivers a bolus of MRTCs, the cells are attenuated, meaning that they pose no risk of further destroying myelin. Instead, the cells die off and remain in situ long enough for the patient’s immune system to recognize the cells as damaging and harmful. With a heightened immune system, the patient’s own healthy T-regulatory cells search for MRTCs to remove them from the body in a sort of “anti-T-cell T-cell response.”
Many facets of this process differentiate Opexa’s therapy from other treatments for multiple sclerosis. Traditional therapies wipe out the entire immune system and target all T-cells and other immune cells for destruction. Tcelna targets a select population of MRTCs, giving the treatment a better side effect profile and greater patient tolerability.
In contrast to the pharmaceutical definition of personalized medicine, Tcelna is truly a personalized medicine. “Pharma looks at ‘personalized’ differently,” commented Warma. “They have a drug candidate that is effective in 10-20% of patients, and they segment the market to serve those patients. At Opexa, we look at all multiple sclerosis patients and find a personalized therapy for every individual.”
Personalization of treatment continues past the first dose of treatment. The optimal dosing schedule was found to be five subcutaneous injections each year, given in the first six months. An injection is given at one, two, three, four, and six months. In the next year, the injection pattern is identical, but patients receive a different formulation of T-cells. “Each of our preparations is tailored specifically to match each individual’s profile. Each patient receives a specialized therapy,” said Warma. “Myelin peptide antigens change over time and are different for every individual. In year two, three, and beyond, we conduct the antigen screening process because we know these myelin peptides shift over time. We deliver a specific T-cell vaccine to each individual, relevant at that time.”
According to Opexa, clinical data so far showed a 37% reduction in annualized relapse rate in patients with RRMS. A sub-population of studied patients with a more progressed/active disease profile saw a statistically significant improvement in disability measured by the Expanded Disability Status Scale (EDSS) score after a year of treatment. In SPMS patients, 80% of patients showed disease stabilization after two years according to the EDSS.
The reasons for improvement are two-fold. First, Tcelna stops destruction of the axonal myelin sheath by depleting the body of MRTCs. Second, Tcelna stops damage to oligodendrocytes, which are the producers of myelin in the central nervous system. “We expect to see stabilization, but we also expect there to be a remyelination process to take place, as MRTCs are no longer destroying the engine that builds myelin,” said Warma. “Clinical data support the hypothesis that preventing destruction of the myelin sheath and oligodendrocytes results in repair. We saw signs of repair, with a clean side effect profile.”
With safety and efficacy bundled together in a personalized T-cell vaccine, Tcelna may be just what the doctor ordered if approved by the Food and Drug Administration for patients with multiple sclerosis.