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PHILADELPHIA -- Multiple sclerosis patients dosed with a monoclonal antibody specific for human endogenous retrovirus (HERV) proteins in a small pilot trial showed signs that the drug helped and was safe, a researcher said here.
After 12 monthly doses of the GNbAC1 antibody, targeting the so-called MRV-Env protein, seven patients with established MS (mean age 55, mean Expanded Disability Scale Score 4.8) showed stability in MRI brain lesion activity and no disability progression on average, according to , of GeNeuro SA in Geneva, Switzerland, which is developing the drug.
Action Points
- One year of therapy with the GNbAC1 antibody, targeting the so-called MRV-Env protein, in seven patients with established multiple sclerosis appeared to be safe and may have contributed to stability of the disease.
Perron said no safety issues were identified in the trial, with most adverse events being those associated with MS disease activity or common complications. He at a poster session at the
Underlying the trial is a theory, not widely accepted in the MS research community, that the disease is caused or exacerbated by activation of certain elements in the normal human genome that, Perron and some others believe, are relics of retroviruses that infected early humans or their primate ancestors millions of years ago.
These small "HERV" elements are not capable of producing fully formed, infectious viruses, but they can express proteins that were components (perhaps now mutated) of the original viral particles, or so the theory goes.
Perron's group believes that MSRV-Env is such a protein -- the name signifying an envelope protein for a hypothetical MS-related retrovirus. Their drug is aimed at suppressing this protein and, with it, disease activity in MS.
A rival group headed by Australia-based , and , is taking a different approach. They are currently enrolling patients in a small trial of the anti-HIV drug raltegravir (Isentress), motivated by case reports along with epidemiological data suggesting that patients on antiretroviral therapy have significantly reduced risk of MS, which can be interpreted as supporting the HERV theory.
Giovannoni told ľֱ that enrollment in his trial was almost complete and that he hoped to have results by the end of 2014.
GNbAC1 Study Details
Perron and colleagues conducted their phase IIa trial in three parts. In the first, they treated 10 patients on a double-blind basis with a single infusion of either 2 or 6 mg/kg of the antibody drug or placebo to measure its pharmacokinetics and gross safety.
When those data generally matched those of an earlier phase I trial in healthy volunteers, the 10 patients were invited to receive monthly open-label infusions of the drug at the same doses (five patients each) for 5 months, with all 10 accepting.
In the third phase, the 10 patients were asked to take another six monthly infusions at the same doses for a total of 12 over a full year. Two of those in the 2-mg/kg group dropped out at this point, but the remaining 8 accepted. (Another in the low-dose group did not undergo all the scheduled MRI scans and was excluded from those analyses but was included in the disability evaluations.)
At month six, four of five patients in the low-d0se group and all five of those receiving the higher dose showed stability in MRI lesion activity. Both arms showed a mean increase of 0.1 EDSS points at this 6-month evaluation, which would not be considered clinically relevant.
The two patients in the low-dose group who underwent all required MRI scans showed continued stability at month 12, as did all five in the high-dose group. Mean EDSS score at month 12 showed a 0.2-point increase from baseline in the three low-dose patients; the five high-dose patients registered a mean decrease of 0.2 points, suggesting clinical improvement in at least one patient. (The EDSS is a categorical measure of increments in disability, mainly in walking.)
Perron told ľֱ that one participant had reported abandoning a wheelchair during the study. However, such reports are not uncommon among patients taking placebo in clinical trials.
One serious adverse event occurred: acute pancreatitis in a patient with a history of biliary disease. Other adverse events ranged from proteinuria to sinus bradycardia. Nine of 140 nonserious events were considered possibly drug-related, Perron and colleagues reported.
No hypersensitivity or infusion reactions were seen, and anti-drug antibodies did not emerge.
Disclosures
The study was funded by GeNeuro. Perron and some co-authors were GeNeuro employees. Perron is a founder of the company.
Other study authors reported financial relationships with GeNeuro.
Primary Source
American Academy of Neurology
Derfuss T, et al "GNbAC1, a Humanized monoclonal antibody against the multiple sclerosis associated retrovirus envelope protein, is well tolerated in patients with multiple sclerosis" AAN 2014; Abstract P2.217.