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FAQ: SIGNAL Trial of VX15 Antibody for Huntington’s Disease (HD)

Below are some frequently asked questions about the SIGNAL Trial for Huntington’s Disease sponsored by Vaccinex and the Huntington Study Group (HSG). SIGNAL is now enrolling subjects in a second phase to determine treatment effects of the VX15 antibody in a larger population of HD subjects.

On April 24, 2017, Vaccinex, Inc. announced preliminary results of testing a novel antibody as a potential therapy for HD. In view of encouraging results, this study has been expanded and is now enrolling an additional 120 late prodromal and early manifest subjects in a second phase of the trial. Click here for full announcement.

Thirty-six participants including both late prodromal and early manifest HD subjects were enrolled at 19 sites in the United States. The VX15 antibody was found to be well-tolerated. Importantly, brain imaging in this study suggested that VX15 antibody treatment preserves brain matter and induces a striking increase in metabolic activity. These findings are the opposite of what is normally observed with the progression of HD.

HD organizations and researchers are interested because the Vaccinex drug showed evidence of an effect on imaging endpoints that have been previously associated with HD progression. These results are encouraging but additional testing in a larger group of HD subjects is required to validate these treatment effects.

Although the results of Cohort A were encouraging, the study was not large enough to demonstrate clinical improvements. Enrollment in Cohort B, the second phase of this study, to test potential clinical benefit is now complete. We do not know yet whether the drug will improve clinical symptoms or slow their progression.

VX15 antibody is a very specific inhibitor of a cellular protein called semaphorin 4D (SEMA4D). Expression of SEMA4D and its receptors are increased in glial cells of the brain when there is an injury to brain tissue, as might, for example, be caused by accumulation of aggregates of mutant huntingtin protein. Glial cells are important to maintain the health and normal function of neurons in the brain. It has been shown in laboratory studies that when SEMA4D binds to its receptor on glial cells, this promotes a transition from normal activity to an inflammatory state. In their inflammatory state, glial cells lose the ability to provide normal support and instead take on new toxic properties that can injure neurons. This may be prevented by blocking the interaction between SEMA4D and its cellular receptors with VX15 antibody. Although, unlike anti-sense oligonucleotide (ASO), VX15 antibody does not directly lower expression of huntingtin protein, by preserving the normal activity of glial cells and other “housekeeping” cells in the brain, VX15 may prevent or reduce disease-associated effects of mutant huntingtin and may also help clear these damaging aggregates from the brain.

VX15 antibody is administered by intravenous infusion in the arm. This was found to be a safe and well-tolerated route of administration for VX15 antibody in the SIGNAL Cohort A and other clinical studies.

The initial clinical trials of VX15 antibody and of ASO are designed to test the benefits of each drug individually. The best way to advance our understanding of these treatments is to enroll in one of these studies so that the effects and potential benefit of each agent can be understood. However, in view of their different mechanisms of action, it is possible that a combination of both drugs may eventually prove to be most effective. This would require testing in a different clinical trial of a drug combination in the future.

In general, it is possible to enroll in successive clinical studies once a drug has “washed-out” of your system. Each clinical study has a specific protocol that defines the required waiting period. In the case of antibodies, like VX15, the waiting period is often a few months, but this will be defined in the specific study protocol.

No. SIGNAL enrollment is complete.

Yes. In June 2018, the United States Adopted Name Council (USAN Council) approved the use of the name, pepinemab, as the official adopted name for the VX15/2503 antibody. The names pepinemab, VX15/2503 and VX15 are synonymous and represent the same investigational drug used in the SIGNAL trial. In the future, the name pepinemab will eventually replace the use of “VX15/2503” and “VX15” in literature and other communications.

Please visit the Vaccinex website for the latest expanded access and compassionate use policy information – http://www.vaccinex.com/company-policy/

Disclaimer: VX15/2503 (pepinemab) is an investigational drug currently in clinical studies. It has not been demonstrated to be safe and effective for treating Huntington’s disease (HD) or for any other disease indication. There is no guarantee that VX15/2503 (pepinemab) will be approved for the treatment of HD by the U.S. Food and Drug Administration, or by any other health authority worldwide.