Vasogen: On the road to commercialization

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By Shawn Lawrence

When Vasogen Inc. first announced in April of 2007 that it had reached an agreement with European pharmaceutical and medical devices company Grupo Ferrer International, S.A., to distribute and sell its lead product Celacade™ to the European market, it marked a major step in Vasogen’s ongoing evolution. Having spent the better part of 16 years developing therapies to target the destructive inflammatory process associated with the progression of cardiovascular and neurodegenerative disorders, this initial commercialization phase of Celacade™ was seen as a sign that Vasogen was ready to expand its business interests commercially.

A year since the landmark agreement was reached, the introduction of the Celacade™ system in Europe has now been put on hold and here in North America the process of putting together a confirmatory study for the technology has encountered significant delays with the US Food and Drug Administration. As such Vasogen has been forced to holding off its plans to fund ACCLAIM II, a clinical trial to support an application for U.S. market approval of Celacade™.
While the news generally isn’t good, it hasn’t dampened Vasogen CEO and president Chris Waddick’s drive to get Vasogen’s products to the market, nor has it made him lose faith in the technology.
“You can say I’m caught up in the passion of what the company is trying to accomplish, and advancing the development of our technologies is at the top of that list,” states Waddick, who first joined the company on a full-time basis in 1997 as its chief financial officer.
On top of serving as Vasogen’s CFO, he has also held several other key roles at the company including executive vice president, chief operating officer from 2005-2007 and was appointed to the role of CEO and president a month after the Grupo Ferrer agreement was reached to steer Vasogen on the road to commercialization.
“I think the fact that at the time of my appointment, we were coming into a period of commercialization, along with my understanding of the technology and how the business was run were all factors in my appointment definitely,” stated Waddick. “I consider myself a business person, and while my background is in finance and business I’ve also grown into the science and clinical side of the role if you will. Spending many years helping to develop these products you’re kind of forced to learn a lot about the science and clinical side of what you’re doing obviously.”
Waddick’s friendship with company co-founder and former Vasogen CEO and president David Elesley, and the time he spent working under him also helped in the grooming process for the role. All of which he believes has given him a significant edge in steering the company through this uncertain time and towards its destination, bringing its therapies to patients.
“I’ve been very fortunate from the very beginning I had the chance to get to understand our technologies, the business, and it has really helped me prepare for this role, and certainly I had the passion and the desire to do it.”
Part of the passion that drives Waddick is his belief that technology underlying Celacade™ and the company’s VP Series of Drugs is strong and despite the delays, he still believes the best course of action is to continue to explore opportunities that support further development in the U.S.
“In a way we are ahead of the curve in this type of research. Our technologies represent a potential first in class therapy for a number of serious medical conditions. The technology is designed to trigger the immune response to ‘apoptosis’ or programmed cell death, an important physiological process that regulates inflammation associated with cardiovascular and neurodegenerative disorders,” he said.
Explaining how Celacade™ works, Waddick says the process involves taking 10 cc. of blood from a patient, putting it inside a medical device where it is stressed by a number of oxidative factors, and then re-administered back into the patient intramuscularly triggering an anti-inflammatory cascade. Oxidative stress is a factor known to initiate apoptosis, a physiologic process that is inherently anti-inflammatory. The company’s VP Series of Drugs are a next generation approach to exploiting this mechanism and offer some key advantages over the device-based approach.
“Certainly there has been a growing interest around the area of apoptosis, and its properties and how they can be potentially exploited in a therapeutic way, we (Vasogen) believe we are one of the first in this industry to grasp the concept and try and exploit it to treat disease. And the best part is, it’s also a very easy process on the patient. The patient is in and out in 30-45 minutes,” he said.
The technology was developed from a scientific concept thought up by one of the co-founders of Vasogen, Dr. Anthony Bolton, who is still with the company as its chief scientific officer. Bolton and the science team spent years of pre-clinical research in animal models looking at the potential of the therapy, developing it, deriving the right treatment regime and then moving it into the clinic and looking at cardiovascular patients and eventually focusing in on the heart failure population.
The aforementioned 2,408-patient Phase III ACCLAIM (Advanced Chronic Heart Failure Clinical Assessment of Immune Modulation Therapy) trial of the Celacade ™ technology, which was completed in 2006 assessed the use of Celacade™ in patients with chronic heart failure, and although the primary endpoint was not achieved, it demonstrated strong results in two important pre-defined patient subgroups showing that it significantly reduced the risk of death or first cardiovascular hospitalization by 39% in patients with NYHA Class II heart failure at baseline (n=689, p=0.0003), and by 26% in patients with no prior history of heart attack at baseline (n=919, p=0.02). It was this study that supported Celacade’s approval status in Europe and allowed Vasogen to seek out Grupo Ferrer International as a partner.
Under the original Vasogen/Ferrer collaboration agreement, Ferrer had the exclusive rights to market Celacade for the treatment of chronic heart failure in specified countries of Europe, including Germany, Spain, Portugal, France and Italy. Additionally Ferrer had exclusive rights to certain countries in Latin America. While this partnership has now been put on hold in terms of its original structure, Waddick still sees it as a strategic fit and the company is currently exploring strategic alternatives with Ferrer.
“One of the key reasons we believe in this partnership and aren’t abandoning it entirely is they have been very successful at introducing new healthcare technologies across Europe in the past. This along with the fact that they are a private company with over a billion dollars in annual revenues and 1/3 of their pharmaceutical business is cardiovascular focused,” he said.
Likewise, the plans to launch the ACCLAIM-II trial, a confirmatory study that was recommended by the US Food and Drug Administration (FDA) to support a U.S. Pre-Market Approval filing for Celacade haven’t been abandoned either.
“We will continue to work with the FDA towards finalizing the design of ACCLAIM II and will evaluate potential strategic alternatives to fund such a study,” he said.
The challenges presented by the uncertainty surrounding the ACCLAIM II trial design including costly delays in initiating this trial, current challenges funding it and resulting impact on Ferrer’s commercialization efforts lead Vasogen to announce a recent restructuring.
“As a result of the Ferrer deal, the company made a transition from a very research focused company, to a company launching a product in a short time. It required us to buildup our expertise and infrastructure in areas we’re not used to focusing on, and adapt to this shift in company focus,” he said. “This was a very exciting and challenging process and only made our recent need to restructure that much more difficult.”
It has lead to some interesting challenges along the way he adds, especially in ensuring the company itself doesn’t lose the entrepreneurial and research drive that got it to this point in the first place.
“It’s about finding the right balance between the two sides, yet continuing to have the entrepreneurial spirit and drive that got us here. In our case especially we have to balance our focus between our late stage products and our earlier stage products also.”
Among these earlier stage products are a new class of drugs Vasogen calls its VP series of drug. The drugs themselves are based on synthetic three-dimensional phospholipid-based structures with specific groups of surface molecules. They are designed to modulate cytokine levels and control inflammation.
“We really developed this class of drugs based on everything we learned developing Celacade. We learned a lot about this apoptotic pathway, how it could be exploited and from that we developed a more synthetic approach to exploiting it. Over the last number of years its been pretty much well accepted that inflammation plays a key role in a number of neuro-inflamatory diseases, so we’ve looked at this in pre-clinical models across disease models such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (Lou Gehrig’s) and diabetic retinopathy. So far the drugs have shown significant effects in all of these models,” said Waddick.
The lead product from the VP Series is VP025 and already Vasogen has completed a successful Phase I clinical trial on VP025 in Canada showing that it was safe and well tolerated.
“This is a product that instead of being delivered by device therapy would come in a vial; it would also be injected intramuscularly. It will be regulated as a biologic as opposed to a device, so we’ll pursue it through a clinical trial pathway likely with a partner as well but primarily focused in North America,” he said.
Additionally VP015, an earlier stage candidate is also being developed to treat inflammatory conditions.
With the status of the Celacade technology up in the air, Waddick states the company will begin to refocus much of its resources on the pushing the VP series through clinical trials. Still he continues to be excited by all of Vasogen’s products and his future plans for the company’s underlying technology haven’t wavered.
“We remain very enthusiastic about developing products that exploit the anti-inflammatory properties of apoptosis. This is an area of science that is gaining a considerable amount of support and given the years of work we have completed in this area we have a huge head start on the competition. Moving our drug program to a very advanced level in one or potentially two neuroinflammatory conditions is a major priority for us.”