Challenges and opportunities in cardiovascular disease

Like other industrialized countries, Canada and Mexico face major challenges in developing and marketing new medical products. In the pharmaceutical sector, pharmaceutical companies and government agencies are working to conclude agreements to facilitate the market entry of clinically tested products approved by public health authorities. 

Given that government financial resources will always be limited, the time required to develop innovative products, and all the steps they have to go through to be approved in terms of efficacy and safety, the process of making them available to the public remains highly demanding. Here we discuss Ceapro Inc, a Canadian biotech company specializing in the development and commercialization of oat-derived active ingredients for the cosmetics and healthcare industries, which continues to expand and develop its two flagship products: oat beta-glucan and avenanthramide.

 

Beta-glucan and Avenanthramide: new therapeutic opportunities

These two products are already present in many well-known brands of cosmetics and personal care products. Oat beta-glucan effectively stimulates collagen synthesis and deeply moisturizes the skin (epidermis and dermis), reducing wrinkles and allowing wounds to heal with minimal scarring. Taken orally, oat beta-glucan reduces bad cholesterol levels and has been recognized by health authorities for its beneficial properties on "heart health" in Canada, the United States, Australia and Europe. Avenanthramide acts as a natural antioxidant, anti-irritant and anti-inflammatory. In oral formulations, it could treat systemic conditions caused by inflammation. Denis Bilodeau, president and owner of iR&D2 Inc. and strategic advisor to Ceapro Inc. tells us in an interview:

 

How long has Ceapro Inc. been involved in new product development, and what are you currently developing in terms of innovation?

Mr. Bilodeau: Ceapro Inc. has been developing products for 26 years; initially, development was focused on ingredients  to serve the cosmetic sector.   In line with the vision of Ceapro’s CEO,  Mr Gilles Gagnon, the company has started to develop the same actives as potential nutraceuticals and pharmaceutical products. Therefore, over the last 8 years, focus has increased on clinical research and retail products, some of which can be sold over the counter in pharmacies, and eventually under a prescription.

Through my company iR&D2 Inc, established 22 years ago, I have the privilege of contributing to the development of Ceapro Inc's products, including beta-glucan and avenanthramide. We work on three levels of innovation. Firstly, the processing of active ingredients through unique proprietary technologies, such as by pressurized gas expansion, is being refined to increase particle granularity and thus improve the dose/effect ratio. Secondly, the creation and development of new formulations imposes dissolution imperatives in line with molecule absorption. We are happy to count on the expertise of our partner Corealis in this respect. Finally, setting up a Phase I study requires assaying the administered molecule. This step requires the involvement of a specialized metabolization laboratory, and we are fortunate to be working with Altasciences on this aspect. 

One of the clinical challenges for Ceapro Inc. is to reduce inflammation as a systemic and circulatory pathology, which has become a major therapeutic theme. Worldwide, 3 out of 5 people die from chronic inflammatory diseases such as stroke, chronic respiratory disease, heart disease, cancer, obesity and diabetes. The prevalence of specific chronic diseases mediated by inflammation is significant. In the case of diabetes, the American Diabetes Association estimates that 30.3 million people, or 9.4% of the US population, had diabetes in 2015, representing the 7th leading cause of death in the United States. As for cardiovascular disease, the American Heart Association reported in 2017 that it accounts for 1 in 3 deaths or around 800,000 deaths in the United States. Globally, cardiovascular disease accounts for 31% of all deaths, and coronary heart disease (CHD) accounts for most CVD deaths, followed by stroke (1 in 20 deaths in the US) and cardiac arrest.

In the case of circulatory systemic inflammation leading to atherosclerosis and typically requiring prescription of statins; eventually, a new, innovative formulation of Ceapro's avenanthramide could become a therapeutic option, as it is less likely to induce side effects such as muscle pain. Ceapro's avenanthramide has already shown benefits in the fight against joint inflammation, and we will shortly be testing it in circulatory inflammation. So there's great potential for this molecule.

 

In December 2022, you received approval from Health Canada to start a Phase I clinical trial at IIA.

Mr. Bilodeau: We call it Phase I-IIA, because Phase I is usually just to determine the maximum tolerated dose, but our aim is to go further and evaluate the signs of activity of the molecule... Normally, after the phase I study, there's a phase II study where efficacy is measured, but we've integrated phase IIA into this study we're running with the Montreal Heart Institute, and we're looking at preliminary signs of response in people with chronic or low-grade systemic inflammation. This is an innovative model that has been approved by Health Canada, and we will start recruiting the first patients this autumn. 

What were the criteria for selecting the Montreal Heart Institute as a partner for this study, and are there any plans to invite other cardiology institutes in other countries?

Mr. Bilodeau: We've had a privileged working relationship with the Montreal Heart Institute for several years. Yes, we could work with other centers in Canada and the United States, but we prefer to pursue and develop our relationship with the Montreal Heart Institute and Dr. Jean-Claude Tardif because of the quality of the work we have received, the high scientific and competency level of his team and the combination of science and clinical proximity to patients. It's a unique facility that brings together all the potential services needed to carry out a study of this nature. So the choice is pretty straightforward. 

 

What are the implications of the study's success once it's completed?

Mr. Bilodeau: The implication is that we would have the basis for a drug capable of reducing inflammation and therefore potentially reducing atherosclerosis with few side effects. This would be a great advantage over other anti-inflammatory drugs. To this end, and at a later date, we will be conducting comparative studies of our drug with other similar drugs.  

 

When do you think it will be marketed in Canada, and do you plan to introduce it in Europe, Latin America and Asia? 

Mr. Bilodeau: We could hope to bring it to market in about 5-7 years. The Phase II-III study alone will take 2-3 years, followed by the regulatory phase. The Phase 1 study has one year left, plus at least two years for our Phase II-III clinical study, and then about 2-3 years for regulatory approval. A global development and commercial partner will be chosen after Phase 2a to handle development and marketing in Canada, the U.S., Europe and abroad.

 

Do you think that Mexico has the necessary conditions to establish a research and development link, i.e. to collaborate in this type of research?

Mr. Bilodeau: Mexico and Canada are both facing growing problems related to inflammatory diseases. In the field of public health, at bilateral, regional and multilateral levels, the 2 countries have created a Canada-Mexico Cooperation Plan (https://www.international.gc.ca/transparency-transparence/mexico-mexique/action-plan.aspx?lang=eng). The first point is that Canada and Mexico will continue to work towards the elimination of barriers to trade in medical supplies, and will continue to share best practices in pandemic management. Secondly, both countries are committed to focusing their efforts on the development of vaccines and medicines, and to working together to ensure access to them on the American continent. Finally, a last point concerns cooperation in the face of future health crises. This is a plan to focus efforts on the development of vaccines and medicines. Facilitating access to developed products remains a major challenge, and bringing them to market remains a major difficulty, because after regulatory approval, there is still what we call formulary approval, i.e. coverage by public and private health insurance. Just because a drug or IT product has been approved by the regulatory authorities doesn't mean it will be reimbursed. This is an important point, especially in the event of a future health crisis. If the efficacy of a drug or software product has been demonstrated, Canada and Mexico should be able to facilitate its availability. At present, the industry understands very well that the resources of the healthcare system are limited, but the hope remains that decision-making will speed up.

 

Finally, would you like to add anything?

Mr. Bilodeau: We're constantly faced with the challenges of speeding up research and converting it into marketed therapeutics. Even if a drug has been developed and approved by the health authorities, it will only be used if the product is extremely advantageous enough to justify its purchase. These challenges explain the high failure rate of new companies, and call for constant creative problem-solving!