New Therapy Targets Skin and Atherosclerosis in Psoriasis

Kate Johnson

March 20, 2012

March 20, 2012 (San Diego, California) — A novel oral immune modulator, known as VB-201, simultaneously improved psoriatic skin lesions and reduced atherosclerotic plaque in a phase 2 study, according to results reported here at the American Academy of Dermatology 70th Annual Meeting.

"We see this as a proof of concept. This is first in class for this novel immune modulator, which has an anti-inflammatory effect in 2 conditions that we see with substantial cooccurrence: psoriasis and atherosclerosis," said principal investigator Alexa Kimball, MD, MPH, from Harvard Medical School in Boston, Massachusetts. Dr. Kimball is also a consultant for VBL Therapeutics in Tel Aviv, Israel, which sponsored the study and developed the drug.

The data support the growing scientific literature suggesting a shared inflammatory component in both psoriasis and cardiovascular (CV) disease and a possible single pathway to treatment.

The mechanism of action of VB-201, an oxidized phospholipid analog from the lecinoxoid molecular class, is thought to be the inhibition of toll-like receptors and monocyte migration, said Dr. Kimball.

"If it is selective to these types of cells, as we think, it is selective to some immune modulation," she explained.

The study randomized 184 patients with moderate to severe psoriasis to 12 weeks of placebo (n = 59), VB-201 20 mg daily (n = 66), or VB-201 80 mg daily (n = 59).

A substudy looked at 47 patients with pronounced atherosclerotic plaque, which was visualized using positron-emission tomography (PET) after injection of 18-fluorodeoxyglucose (FDG).

In general, study participants were around 45 years of age, had a body mass index of around 29 or 30 kg/m², a baseline Psoriasis Area and Severity Index (PASI) score approaching 20, and a disease duration of 15 to 20 years, said Dr. Kimball.

In the substudy, subjects with atherosclerosis were about 5 years older and had a number of comorbidities, including vascular disease, dyslipidemia, diabetes, and obesity.

Results were underwhelming for the primary end points of the main study, including improvements in the PASI, Patient Global Assessment, and Physician Global Assessment scores, Dr. Kimball reported.

"This is not a drug that is reaching high levels of PASI 90 and PASI  100, but there is some benefit. This drug is moving people from substantial severity to reduced severity. It may not be the drug that clears everyone's psoriasis to 0, but you can see substantial differences between baseline and 12 weeks, moving a reasonable number of patients out of the severe category," she said.

However, the substudy met the primary end point for atherosclerotic inflammation. It showed "an elegant dose response," with a reduction in inflammation from baseline of 7.3% in the 20 mg group and 12.7% in the 80 mg group, compared with 4.0% in the placebo group.

"To put that into context, with high-dose statin therapy, you would typically see responses in the 7% to 10% reduction range, and that's usually over 6 months; this is occurring over just 3 months," she said.

FDG–PET scans were used to measure "the most inflamed section of the most inflamed vessel" for the primary end point, and overall inflammation and peaks in the great vessels in general, she explained.

"This form of PET/CT has been shown to be a pretty sensitive measure for inflammation in these vessels and is being used in investigational settings to try to find a surrogate marker for CV risk," she said. Changes on imaging correlate with histopathologic inflammation and CV risk factors, and seem to be predictive of future CV events, she noted.

Importantly, many of the patients who entered the study were already on statin therapy, suggesting that VB-201 might offer further improvement. "Knowing that cardiovascular risk factors are a huge public health problem, this type of approach may have multiple benefits for [our patients with psoriasis] going forward."

There were no serious adverse events associated with the therapy, and only mild intestinal complaints, she said.

I don't have a lot of information on this new agent. From what little I could glean, the potential target is very early in the inflammatory pathway, and it's an inflammatory pathway that might be more active in atherosclerosis than psoriasis," said Richard L. Gallo, MD, PhD, professor and chief of dermatology at the University of California at San Diego, and moderator of the session at which the study was presented.

This agent offers a welcome alternative to other psoriasis therapies, such as tumor necrosis factor (TNF)-alpha inhibitors, which can reduce atherosclerotic inflammation, said Maria Hordinsky, MD, chair of the Department of Dermatology at the University of Minnesota in Minneapolis, who also moderated the session.

This is a possible alternative for people who are not able to tolerate TNF-alpha inhibitors," she told Medscape Medical News. "Although TNF-alpha inhibitors haven't been around that long, and even though they're considered very safe, in a tertiary care center, we start to see the oddball cases [of intolerance]."

She said that the increasing evidence of potentially shared pathways for psoriasis and atherosclerosis might open new partnerships.

"The synergy between cardiology and dermatology is going to happen in a broader way across the country. Will we partner more with cardiologists? Are we going to do more PET scans? I don't know," she said.

The study was sponsored by VBL Therapeutics, the manufacturer of VB-201. Dr. Kimball reports being a consultant and investigator for VBL Therapeutics; and receiving grants, consulting honoraria, and speaker's fees from numerous other companies. Dr. Gallo reports receiving consulting fees from Allergan and Novartis; receiving investigator grants from Colgate-Palmolive, Galderma Laboratories, L.P., Intendis, Johnson & Johnson Consumer Products, and L'Oreal USA; and being a founder and stockholder of Skin Epibiotics. Dr. Hordinsky reports receiving grants as an investigator for Allergan, Astellas Pharma US, Johnson & Johnson Consumer Products, Lexington International, Medicis Pharmaceutical, and Novartis Pharmaceuticals.

American Academy of Dermatology (AAD) 70th Annual Meeting: Late-breaking abstract. Presented March 16, 2012.


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