Investigational Psoriasis Drug Reduces Vessel Inflammation

SAN DIEGO – An investigational first-in-class drug not only improved plaque psoriasis but reduced atherosclerotic inflammation in major vessels, a study has shown.

At 12 weeks there was a dose-related response in inflammation in the most-diseased vessels. Those in the placebo group had a 4% decrease in the target-to-baseline ratio (a validated PET/CT measure of changes in vessel inflammation), while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"As we look at our patients with psoriasis, where cardiovascular risk factors are a huge public health problem, this type of approach may have multiple benefits for them," said Dr. Alexa B. Kimball, who presented the results at the annual meeting of the American Academy of Dermatology.

The results come from a phase II trial of 184 patients with moderate to severe plaque psoriasis and a PET/CT substudy of 47 patients with cardiovascular risk factors. The patients in the double-blind, randomized, placebo-controlled study received either 20 or 80 mg of VB-201 or placebo once daily for 12 weeks.

VB-201, a phospholipid analogue, is being developed by VBL Therapeutics as an oral disease-modifying agent for chronic immunoinflammatory disease and atherosclerosis inflammation, and is the first in the lecinoxoid molecular class.

The compound’s novel mechanism of action for the control and attenuation of chronic immunoinflammatory diseases is thought to be through the highly selective modulation of components of the innate immune system. The drug is proposed to work by inhibiting cell-surface toll-like receptor signal cascade. "It’s mimicking some of the native molecules, but this turns out to be specific to antigen-presenting cells, endothelial cells, and monocytes," said Dr. Kimball. Thus, chemokine-mediated migration of monocytes to inflamed tissue is limited.

In the subanalysis, patients had to have a target-to-baseline ratio on PET/CT scan that was greater than 1.6 in order to be eligible.

PET/CT was used to evaluate inflammation in the vessels over time. The primary endpoint in this substudy included the mean of the maximum values of the target-to-baseline ratio in the most-diseased segment of vessel. The secondary endpoint involved looking at all of the inflammation in the vessels to determine a mean value for the vessels in a given patient; these mean values were then used to calculate an overall mean value of inflammation.

"One of the challenges in cardiovascular studies looking at atherosclerotic disease is that the endpoint that you’re most interested in is actually myocardial infarction, typically," said Dr. Kimball. "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 be a surrogate marker for risk."

In addition, the technique correlates well with histopathologic inflammation and with cardiovascular risk factors. "It also seems to be predictive of future clinical vascular events," she said. High-fluorine-¹⁸fluorodeoxyglucose uptake appears to correlate with future vascular events.

"We did enhance the substudy with patients with additional cardiovascular risk factors to make sure that we had a population at risk where we actually could see inflammation to begin with," she said.

In the substudy, 13 patients were on placebo, 18 were on 20 mg VB-201, and 16 were taking 80 mg VB-201. These patients were a little older and had such risk factors as vascular disease dyslipidemia, diabetes, and obesity. Many were on statins.

At 12 weeks, there was a dose-related response in inflammation in the most-diseased vessel. Those in the placebo group had a 4% decrease in target-to-baseline ratio, while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"To put that into context with high-dose statin therapy, we would typically see these types of responses in the 7%-10% reduction range usually over 6 months rather than just 3 months," said Dr. Kimball of the dermatology department at Massachusetts General Hospital in Boston.

In the main study, the researchers looked at the effects of the drug on plaque psoriasis, compared with placebo. The primary endpoint was a Psoriasis Area and Severity Index (PASI) score of 75.

The 184 patients were randomized to receive 20 mg VB-201 (66), 80 mg VB-201 (59), or placebo (59). The study cohort was primarily composed of overweight men (BMI approximately 30 kg/m²) with an average age of 45 years. Overall, the group had a baseline PASI score close to 20.

Statistically significant improvements were achieved on the Physician Global Assessment and Patient Global Assessment. In terms of PASI 75, "there was a dose response as well," said Dr. Kimball. "This is not a drug that is achieving high levels of PASI 90 or PASI 100 ... but there is some benefit."

"This drug is moving people from substantial severity to reduced severity ... It may not be a drug that clears psoriasis to zero, but you can move patients out of the severe category," she said.

"VBL-201 is thought to be – at least in these initial studies – quite well tolerated. ... The study met its primary endpoint in the PET-CT substudy, demonstrating a statistically significant reduction in vascular inflammation," Dr. Kimball noted. "Importantly, these reductions occurred also in patients who were on statin therapy."

There were no treatment-related serious adverse events; the overall rates of adverse events were similar for both doses of VB-201 drug and placebo.

The study was funded by VBL Pharmaceuticals. Dr. Kimball is a consultant for VBL and several other pharmaceutical companies.

SAN DIEGO – An investigational first-in-class drug not only improved plaque psoriasis but reduced atherosclerotic inflammation in major vessels, a study has shown.

At 12 weeks there was a dose-related response in inflammation in the most-diseased vessels. Those in the placebo group had a 4% decrease in the target-to-baseline ratio (a validated PET/CT measure of changes in vessel inflammation), while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"As we look at our patients with psoriasis, where cardiovascular risk factors are a huge public health problem, this type of approach may have multiple benefits for them," said Dr. Alexa B. Kimball, who presented the results at the annual meeting of the American Academy of Dermatology.

The results come from a phase II trial of 184 patients with moderate to severe plaque psoriasis and a PET/CT substudy of 47 patients with cardiovascular risk factors. The patients in the double-blind, randomized, placebo-controlled study received either 20 or 80 mg of VB-201 or placebo once daily for 12 weeks.

VB-201, a phospholipid analogue, is being developed by VBL Therapeutics as an oral disease-modifying agent for chronic immunoinflammatory disease and atherosclerosis inflammation, and is the first in the lecinoxoid molecular class.

The compound’s novel mechanism of action for the control and attenuation of chronic immunoinflammatory diseases is thought to be through the highly selective modulation of components of the innate immune system. The drug is proposed to work by inhibiting cell-surface toll-like receptor signal cascade. "It’s mimicking some of the native molecules, but this turns out to be specific to antigen-presenting cells, endothelial cells, and monocytes," said Dr. Kimball. Thus, chemokine-mediated migration of monocytes to inflamed tissue is limited.

In the subanalysis, patients had to have a target-to-baseline ratio on PET/CT scan that was greater than 1.6 in order to be eligible.

PET/CT was used to evaluate inflammation in the vessels over time. The primary endpoint in this substudy included the mean of the maximum values of the target-to-baseline ratio in the most-diseased segment of vessel. The secondary endpoint involved looking at all of the inflammation in the vessels to determine a mean value for the vessels in a given patient; these mean values were then used to calculate an overall mean value of inflammation.

"One of the challenges in cardiovascular studies looking at atherosclerotic disease is that the endpoint that you’re most interested in is actually myocardial infarction, typically," said Dr. Kimball. "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 be a surrogate marker for risk."

In addition, the technique correlates well with histopathologic inflammation and with cardiovascular risk factors. "It also seems to be predictive of future clinical vascular events," she said. High-fluorine-¹⁸fluorodeoxyglucose uptake appears to correlate with future vascular events.

"We did enhance the substudy with patients with additional cardiovascular risk factors to make sure that we had a population at risk where we actually could see inflammation to begin with," she said.

In the substudy, 13 patients were on placebo, 18 were on 20 mg VB-201, and 16 were taking 80 mg VB-201. These patients were a little older and had such risk factors as vascular disease dyslipidemia, diabetes, and obesity. Many were on statins.

At 12 weeks, there was a dose-related response in inflammation in the most-diseased vessel. Those in the placebo group had a 4% decrease in target-to-baseline ratio, while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"To put that into context with high-dose statin therapy, we would typically see these types of responses in the 7%-10% reduction range usually over 6 months rather than just 3 months," said Dr. Kimball of the dermatology department at Massachusetts General Hospital in Boston.

In the main study, the researchers looked at the effects of the drug on plaque psoriasis, compared with placebo. The primary endpoint was a Psoriasis Area and Severity Index (PASI) score of 75.

The 184 patients were randomized to receive 20 mg VB-201 (66), 80 mg VB-201 (59), or placebo (59). The study cohort was primarily composed of overweight men (BMI approximately 30 kg/m²) with an average age of 45 years. Overall, the group had a baseline PASI score close to 20.

Statistically significant improvements were achieved on the Physician Global Assessment and Patient Global Assessment. In terms of PASI 75, "there was a dose response as well," said Dr. Kimball. "This is not a drug that is achieving high levels of PASI 90 or PASI 100 ... but there is some benefit."

"This drug is moving people from substantial severity to reduced severity ... It may not be a drug that clears psoriasis to zero, but you can move patients out of the severe category," she said.

"VBL-201 is thought to be – at least in these initial studies – quite well tolerated. ... The study met its primary endpoint in the PET-CT substudy, demonstrating a statistically significant reduction in vascular inflammation," Dr. Kimball noted. "Importantly, these reductions occurred also in patients who were on statin therapy."

There were no treatment-related serious adverse events; the overall rates of adverse events were similar for both doses of VB-201 drug and placebo.

The study was funded by VBL Pharmaceuticals. Dr. Kimball is a consultant for VBL and several other pharmaceutical companies.

SAN DIEGO – An investigational first-in-class drug not only improved plaque psoriasis but reduced atherosclerotic inflammation in major vessels, a study has shown.

At 12 weeks there was a dose-related response in inflammation in the most-diseased vessels. Those in the placebo group had a 4% decrease in the target-to-baseline ratio (a validated PET/CT measure of changes in vessel inflammation), while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"As we look at our patients with psoriasis, where cardiovascular risk factors are a huge public health problem, this type of approach may have multiple benefits for them," said Dr. Alexa B. Kimball, who presented the results at the annual meeting of the American Academy of Dermatology.

The results come from a phase II trial of 184 patients with moderate to severe plaque psoriasis and a PET/CT substudy of 47 patients with cardiovascular risk factors. The patients in the double-blind, randomized, placebo-controlled study received either 20 or 80 mg of VB-201 or placebo once daily for 12 weeks.

VB-201, a phospholipid analogue, is being developed by VBL Therapeutics as an oral disease-modifying agent for chronic immunoinflammatory disease and atherosclerosis inflammation, and is the first in the lecinoxoid molecular class.

The compound’s novel mechanism of action for the control and attenuation of chronic immunoinflammatory diseases is thought to be through the highly selective modulation of components of the innate immune system. The drug is proposed to work by inhibiting cell-surface toll-like receptor signal cascade. "It’s mimicking some of the native molecules, but this turns out to be specific to antigen-presenting cells, endothelial cells, and monocytes," said Dr. Kimball. Thus, chemokine-mediated migration of monocytes to inflamed tissue is limited.

In the subanalysis, patients had to have a target-to-baseline ratio on PET/CT scan that was greater than 1.6 in order to be eligible.

PET/CT was used to evaluate inflammation in the vessels over time. The primary endpoint in this substudy included the mean of the maximum values of the target-to-baseline ratio in the most-diseased segment of vessel. The secondary endpoint involved looking at all of the inflammation in the vessels to determine a mean value for the vessels in a given patient; these mean values were then used to calculate an overall mean value of inflammation.

"One of the challenges in cardiovascular studies looking at atherosclerotic disease is that the endpoint that you’re most interested in is actually myocardial infarction, typically," said Dr. Kimball. "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 be a surrogate marker for risk."

In addition, the technique correlates well with histopathologic inflammation and with cardiovascular risk factors. "It also seems to be predictive of future clinical vascular events," she said. High-fluorine-¹⁸fluorodeoxyglucose uptake appears to correlate with future vascular events.

"We did enhance the substudy with patients with additional cardiovascular risk factors to make sure that we had a population at risk where we actually could see inflammation to begin with," she said.

In the substudy, 13 patients were on placebo, 18 were on 20 mg VB-201, and 16 were taking 80 mg VB-201. These patients were a little older and had such risk factors as vascular disease dyslipidemia, diabetes, and obesity. Many were on statins.

At 12 weeks, there was a dose-related response in inflammation in the most-diseased vessel. Those in the placebo group had a 4% decrease in target-to-baseline ratio, while those on 20 mg and 80 mg of VB-201 had decreases of 7% and 13%.

"To put that into context with high-dose statin therapy, we would typically see these types of responses in the 7%-10% reduction range usually over 6 months rather than just 3 months," said Dr. Kimball of the dermatology department at Massachusetts General Hospital in Boston.

In the main study, the researchers looked at the effects of the drug on plaque psoriasis, compared with placebo. The primary endpoint was a Psoriasis Area and Severity Index (PASI) score of 75.

The 184 patients were randomized to receive 20 mg VB-201 (66), 80 mg VB-201 (59), or placebo (59). The study cohort was primarily composed of overweight men (BMI approximately 30 kg/m²) with an average age of 45 years. Overall, the group had a baseline PASI score close to 20.

Statistically significant improvements were achieved on the Physician Global Assessment and Patient Global Assessment. In terms of PASI 75, "there was a dose response as well," said Dr. Kimball. "This is not a drug that is achieving high levels of PASI 90 or PASI 100 ... but there is some benefit."

"This drug is moving people from substantial severity to reduced severity ... It may not be a drug that clears psoriasis to zero, but you can move patients out of the severe category," she said.

"VBL-201 is thought to be – at least in these initial studies – quite well tolerated. ... The study met its primary endpoint in the PET-CT substudy, demonstrating a statistically significant reduction in vascular inflammation," Dr. Kimball noted. "Importantly, these reductions occurred also in patients who were on statin therapy."

There were no treatment-related serious adverse events; the overall rates of adverse events were similar for both doses of VB-201 drug and placebo.

The study was funded by VBL Pharmaceuticals. Dr. Kimball is a consultant for VBL and several other pharmaceutical companies.