Tcelna™ (formerly Tovaxin®)
Experimental Medications: Other Therapeutic Strategies
Company: Opexa Therapeutics
- Given via five subcutaneous injections per year
- Has been studied in SPMS
Tcelna is a T-cell vaccine. In the process of administering this vaccine, myelin-reactive T cells are removed from a small amount of the patient’s blood, inactivated, and then injected back into the patient. The body’s immune system may then potentially protect the myelin from these cells.
The TERMS placebo-controlled, one-year study in 150 people with clinically isolated syndrome (CIS) and RRMS to evaluate Tcelna’s efficacy, safety, and tolerability has been completed. The treatment did not achieve statistical significance in the primary endpoint, which was a reduction in the cumulative number of gadolinium-enhancing lesions.
However, a 37 percent decrease was seen in the annualized relapse rate of individuals given Tcelna versus placebo. The drug was well tolerated with mild skin reactions in some individuals; no serious safety concerns were raised by this study. In a subgroup of 70 people who had at least one relapse in the 12 months prior to enrolling in the study and who had no previous exposure to MS therapy, Tcelna reduced their annualized relapse rate by 64 percent compared to placebo. Additionally, 76 percent of Tcelna-treated patients remained relapse-free at one year compared with 60 percent of placebo patients.
Tcelna was more recently studied in a Phase II trial in SPMS, the Abili-T study.29 Abili-T enrolled 183 individuals with SPMS in a placebo-controlled two-year trial. The Abili-T study results were reported in a press release in October 2016. Unfortunately, the study did not find a reduction in brain atrophy (the primary endpoint) or in disability progression (the secondary endpoint) in the individuals given Tcelna versus placebo. Although vaccines are an attractive strategy in MS treatment, to date there is not any convincing evidence that they have the potential for becoming an effective therapy option.
The tetracycline antibiotics, including minocycline and doxycycline, have immunomodulatory and neuroprotective activities. They appear to decrease the passage of lymphocytes across the blood-brain barrier. In 2009, a small double-blind, placebo-controlled Phase II trial of Copaxone plus minocycline showed favorable magnetic resonance imaging (MRI) data, with minocycline decreasing gadolinium-enhancing activity by 50 percent over a period of six months. A subsequent 24-month trial showed a significant decrease in lesion activity and clinical status.
A larger study called RECYCLINE enrolled 305 individuals with RRMS and used minocycline as an add-on to Rebif in people with RRMS. Data were presented at ECTRIMS in 2012,30 and disappointingly, minocycline did not provide significant improvement to either clinical or MRI outcomes.
Another Phase III trial looking at minocycline reported positive data in fall 2015. This Canadian Phase III double-blind study began in 2009, and enrolled 142 people with a clinically isolated syndrome (CIS). The participants were randomized to oral minocycline at 100 mg twice daily or to an identical placebo. Treatment was continued for up to two years, or until MS was confirmed. Those receiving minocycline had a 44.6 percent lower risk of conversion to MS at six months, and a 37.6 percent lower risk at 12 months, versus individuals taking a placebo. The authors suggest that with the known safety and low cost of minocycline, this medication could be considered for the initial treatment of individuals with a first clinical demyelinating event, particularly in geographic regions without access to approved disease-modifying therapies.