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Disease management to disease modification – removing plaque to undo atherosclerosis:

Atherosclerosis

Author

Natasza Klas

Scientific Writer/Analyst
Market Intelligence Unit, Longevity.Technology
Author

Girish Harinath

Scientific Editor
Market Intelligence Unit, Longevity.Technology
  • Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of plaque within arteries. The leading cause of death globally, atherosclerosis accounts for over 40% of all deaths worldwide.
  • Currently, the cholesterol-lowering drugs prescribed to tackle atherosclerosis do not address the underlying cause of the disease, or reverse the atherosclerotic plaques already formed. As the burden of atherosclerosis related diseases continues to grow, novel solutions for treatment are becoming necessary.
  • Cyclarity is developing genuine “disease-modifying” solutions to address age related diseases, such as atherosclerosis, by repairing an underlying cause common to many of them: the inevitable accumulation of toxic biomolecules inside cells over time.
  • Cyclarity’s primary candidate, UDP-003 is a specially-engineered beta-cyclodextrin designed to target and remove toxic, oxidized cholesterol – a key driver of atherosclerosis.
  • Without doubt, Cyclarity’s approach to true disease medication, and therefore reversal of age-related disease, offers a great deal of promise for investors, healthcare systems in the US and globally, and, most of all, for those affected by atherosclerosis-related disease.

Cardiovascular disease and atherosclerosis: the silent killer

Cardiovascular disease (CVD) is the #1 cause of death globally and encompasses a broad set of over a dozen disorders that compromise the function of the heart and blood vessels. The major cause of CVD by far, however, is the pathological process of atherosclerosis (CDC, 2022). Like the accumulation of rust within pipes, atherosclerosis involves the gradual build up of plaque within arteries which compromises the flow of blood and oxygen in the body. Strikingly, atherosclerosis is responsible for more than 40% of all deaths worldwide, and 80% of those deaths are in individuals 65 years and older. This includes mortality from devastating pathologies that are among the leading causes of death like coronary artery disease, chronic obstructive pulmonary disorder and stroke (Pahwa, 2022).

Unbeknownst to many, the process of atherosclerosis begins during early childhood. As we age, plaque builds up extensively and eventually ruptures, inducing blood clots that completely block blood flow through arteries (Goldman, 2018). Often undiagnosed, the consequences of atherosclerosis can be sudden and fatal cardiovascular events that traumatize families and exhaust healthcare systems around the world. Due to its gradual and insidious nature, a significant percentage of individuals are unaware they have cardiovascular disease until they have a heart attack. Further, it is estimated that 45% of heart attacks are silent; individuals do not notice any symptoms, yet the damage is done. Heart attacks drastically increase the risk of sudden cardiac arrest (SCA) and 90% of SCAs that happen outside hospital settings end in fatality. This has earned heart disease the notorious title – “the silent killer” (Virani, 2021).

The Center for Disease Control and Prevention estimates that the US spends $219B each year on improving metabolic health and managing symptoms of heart disease in the hopes of dethroning humankind’s most infamous killer; this alone makes it the most expensive disease to treat in the US. [Current drug treatments focus solely upon (a) lipid management, and (b) management (BP med, blood thinner) to help prevent major cardiac events.]

The conventional approach: disease management

The development of therapeutics to combat atherosclerotic CVD forms a significant part of humankind’s battle against chronic disease. The basic pathological process of atherosclerosis has been characterized for over a century (Figure 2). Despite its multifaceted nature, the major clinical focus for treatment of atherosclerosis has involved targeting cholesterol metabolism to reduce the rate of plaque accumulation within blood vessels or improving recovery after a cardiovascular event (Table 1). Of all therapeutic interventions, cholesterol-lowering statins dominate the CVD market. In fact, statins are the most commonly-prescribed drug in the world (Finnegan, 2018). In essence, the field of CVD therapeutics has adopted a strategy of slowing the rate of disease progression and reducing the risk of complications from disease (i.e. cardiovascular events, like heart attacks). Although this strategy has played a role in the significant increase in average human lifespan over the past century, it is essentially a disease management approach that has failed to erase CVD from the list of humanity’s most prolific killers.

ClassGoalTherapeutic Interventions
Cholesterol lowering drugSlow down disease progression, reduce cardiovascular eventsStatins, CETP inhibitors, PCSK9 inhibitors
BP lowering drugsSlow down disease progression, reduce cardiovascular eventsACE inhibitors, Diuretics, Beta blockers, Angiotensin II receptor blockers
Cardiovascular trauma recoveryCardiovascular event recoveryStents, Bypass surgery, Angioplasty, Clot busters, Anti-platelet drugs
Plaque removal, ImmunotherapyReverse atherosclerosisEngineered cyclodextrins
Table 1 – Classes of CVD therapeutics: Standard of care includes therapeutics that improve metabolic health (cholesterol and blood pressure lowering drugs as well as interventions for recovery from cardiovascular trauma. Cholesterol and BP lowering drugs are targeted towards slowing down CVD progression and reducing cardiovascular events. Cardiovascular trauma recovery involves stents and clot busters that treat symptoms of disease. Cyclarity’s lead candidate is a “first of its kind” drug for plaque removal and immune cell rejuvenation. It is the only intervention of its class that has potential to reverse atherosclerosis progression and reboot the cardiovascular system to a youthful state.

Top 3 leading causes of death in the US

Chart shows number of deaths (Y axis) plotted against the year (X axis)

Figure 1 – Leading cause of death from 2001-2019 and statin use: Despite statin use nearly doubling in the past 20 years, cardiovascular disease remains the leading cause of death. Cardiovascular disease continues to kill nearly 200,000 more people than the number 2 leading cause of death, cancer. The incidence of CVD mortality has been steadily rising since 2011 (ironically, since statin use nearly doubled) and is the highest it has been in several decades (Roser, 2022)

In spite of incredible biomedical advances and hundreds of billions of dollars of investment in developing drugs that target cholesterol metabolism, atherosclerosis continues to kill more humans than anything else. (Figure 1). This includes infectious disease, cancer, and diabetes. This trend shows no signs of slowing down, as the incidence of atherosclerosis and cardiovascular disease has been steadily increasing for the past three decades (Roser, 2022). It is time for the field of cardiovascular therapeutics to reevaluate its approach and reduce its fixation on disease management and to consider the possibility of genuine disease modification – but what would an approach like this even look like?

Figure 2 – Atherosclerosis Master Figure: Graphic illustrating the multi-faceted, pathological process of atherosclerosis. Standard of care either targets too early/upstream (only to slow the disease progression) or intervenes too downstream (to facilitate recovery post cardiovascular event). Cyclarity’s drug UDP-003 works in the “Goldilocks” zone, targeting the root cause and leading to disease reversal. 1) Cholesterol flowing through healthy blood vessel. 2) Cholesterol gets into walls of blood vessel. 3) Cholesterol gets damaged/oxidized within walls of blood vessel, making it toxic. (ROOT CAUSE) 4) Macrophages (immune cells) engulf oxidized cholesterol, but can not degrade it, transforming them into pathological foam cells/plaque. Undamaged cholesterol is easily degraded by macrophages. 5) Foam cells secrete inflammatory factors that drive inflammaging and accelerate plaque accumulation (COMPOUNDING EFFECT) creating a vicious cycle of disease progression. 6) Plaque ruptures and blocks blood flow through vessel, leading to cardiovascular event.

Cyclarity’s approach: disease modification

While high cholesterol levels in the blood is clearly a significant contributor and risk factor for CVD, clinical research within the past two decades is revealing that it is far from the complete picture. This is because there are several downstream events that transform this essential metabolite into a toxic waste product. Most importantly, the development of atherosclerosis is contingent upon cholesterol penetrating blood vessels and becoming oxidized – making it non-degradable and toxic.

This corrupted form of cholesterol ultimately drives an insidious cycle of low level chronic inflammation (inflammaging), macrophage dysfunction, and plaque accumulation (Figure 2) (He, 2022). There is a rapid body of evidence amassing in support of inflammaging as a key, unifying driver of several age-related diseases and, indeed, the process of aging itself. In this sense, atherosclerosis may be more accurately described as “a smoldering inflammatory condition that is aggravated by cholesterol” (Tsoupras, 2018). A true disease modification approach requires targeting and remedying these pathological features of atherosclerosis, an endeavor that no company to date has successfully demonstrated.

Cyclarity Therapeutics is an innovative biopharmaceutical company that seeks to address age-related diseases by repairing an underlying cause common to many of them: the accumulation of toxic biomolecules inside of cells. Cyclarity’s initial focus is restoring cardiovascular health through removing the cellular trash that gives rise to immune cell dysfunction, inflammation, and plaque accumulation within blood vessels. This is in stark contrast to the conventional focus on disease management through slowing plaque accumulation or reducing the risk of cardiovascular events. At its roots, atherosclerosis is a disease that begins within cells – not in the plasma. Adopting an engineering approach to remove damage and repair cells, Cyclarity seeks to offer the first genuinely disease-modifying drug for atherosclerosis. Cyclarity’s ground-breaking therapeutic, a drug called UDP-003, holds promise to radically reduce the trillion-dollar burden of this condition and save countless lives (Garth, 2022).

Redefining the treatment paradigm for atherosclerosis

Since atherosclerosis was first characterized in the early 20th century, the field of cardiovascular therapeutics has operated with a rigid, ameliorative strategy for addressing cardiovascular pathology; the development and gradual improvement of interventions focused on slowing down the process of atherosclerosis, reducing cardiovascular events, and supporting event recovery (Minelli, 2020).

Cyclarity Therapeutics works instead to rehabilitate the cardiovascular system’s own, natural self-repair mechanism, removing the toxic byproducts that cause macrophage dysfunction and restoring their natural ability to manage and reduce plaque. This is a “first in class” therapy that could redefine the treatment paradigm for atherosclerosis, paving a path for a new class of disease-modifying therapeutics. For the first time in the history of mankind’s fight against chronic disease, the possibility of disease reversal has been enabled.

There are several pivotal factors that lend great promise to Cyclarity’s lead candidate UDP-003:

  • Unique biological properties: UDP–003 belongs to a class of compounds known as cyclodextrins. Cyclodextrins have special chemical properties that give them powerful fat/cholesterol binding capabilities (Szente, 2016).
  • Robust safety profile: Cyclodextrins are a well known class of compounds used in common household and food products, as well as a pharmaceutical ingredient used to enhance the delivery of dozens of FDA approved drugs (American Chemical Society, 2015).
  • Precision engineered: Cyclarity uses its novel computational platform technology to engineer cyclodextrins to enhance target specificity, safety, and efficacy relative to generic cyclodextrins.
  • UDP-003 clears away plaque (refer to Figure 1): UDP-003 is designed to precisely bind and clear a toxic form of oxidized cholesterol, 7-ketocholesterol (7-KC), that builds up in immune cells (macrophages), transforming them into foam cells – the root cause of plaque formation.
  • UDP-003 is an immunotherapy that restores the cardiovascular system’s natural self-repair system (refer to Figure 1): The transformation of macrophages into foam cells is the critical transition point that drives plaque formation. The factors foam cells secrete drive inflammaging, a central mediator and compounding factor of atherosclerosis. By clearing out oxidized cholesterol from foam cells, UDP-003 has been shown to restore macrophages back to their functional state (National Institute of Aging, 2021).

Winning Strategy

Beyond UDP-003, there are several key features to Cyclarity’s strategy that set it up for success as a biopharmaceutical trailblazer within a challenging disease market:

  • Disruptive platform technology: Cyclarity’s platform technology designs, predicts, builds, and tests the ability of cyclodextrins to bind target molecules. This saves significant money, time, and resources by simulating and anticipating results before synthesis, benchwork, and clinical testing. Further, it facilitates iteration and evolution of Cyclarity’s pipeline to target other cellular waste products and indications.
  • Strong regulatory advantage: In recognition of its groundbreaking therapeutic strategy and promising preclinical results for UDP-003, Cyclarity was recently awarded an Innovation Passport under the United Kingdom’s Innovative Licensing and Access Pathway (ILAP). This has the potential to significantly accelerate progression and reduce costs of the clinical trial process, one of the biggest hurdles for up and coming biopharma companies (Garth, 2022).
  • Complementary combinatorial potential (constructive disruption): Due to its unique mechanism of action, UDP-003 should be complementary with standard of care therapeutics. Using a complementary approach may allow Cyclarity to “constructively disrupt” the CVD market by adding more effective and cost-reducing treatments without the need to immediately challenge standard of care.
  • World class team: Cyclarity is headed up by leaders in the longevity field supported by critical partnerships with the premier engineers of custom cyclodextrins and the world’s leading specialists in the development of cyclodextrin-specific simulations. Currently, Cyclarity is the only company that is engineering cyclodextrins to improve their precision, efficacy, and applicability for targeting age-related diseases. Their experienced in-house team and exceptional external partnerships promises to keep them ahead of their competition.

Cyclarity possesses several unique attributes that can help catalyze the global shift into an era of longevity [Table 2].

Consequences of a “sick care” systemCyclarity’s solution
CVD represents a tremendous burden on global morbidity and mortality with an aging population.Cyclarity’s lead candidate UDP-003 is designed to reverse atherosclerosis by clearing out plaque and restoring the cardiovascular system’s natural self-repair system, with the prospects of rejuvenation.
Diseases are addressed in isolation, yet cellular waste (i.e. oxidized cholesterol) and processes such as inflammaging are common drivers of several age-related diseases. Longevity drugs aim to tackle several age-related diseases by addressing common aging mechanisms.UDP-003 is delivered systemically to remove oxidized cholesterol (particularly 7-KC) from foam cells, restoring immune health and addressing one of the major “hot spots” of inflammaging. Cyclarity’s platform technology has potential to identify and engineer molecules that clear multiple forms of cellular trash and target several different indications.
Plaque begins accumulating in arteries at a very young age. Individuals with “normal plaque burden for their age” are sick patients that have not been classified as sick yet. Early intervention is the key to healthy longevity.Cyclarity’s ultimate goal is to offer UDP-003 as part of a preventative regimen to incrementally clear out plaque before it becomes a problem. Cyclarity aims to develop novel biomarker assays for example ones that measure cardiovascular aging well below the detection limit of current clinical diagnostics.
Aging is not considered a process that can be targeted. The FDA must classify aging as an indication to put longevity medicine “on the map” and make it available to the general public.Cyclarity’s unique therapeutic strategy and recent ILAP award promises to help it move more effectively through clinical trial phases while demonstrating a geroscience/SENS approach. In doing so, Cyclarity would help optimize and integrate a longevity strategy within the pharma regulatory framework.
Table 2 – The consequence of “sick care” system and the solution that Cyclarity could provide.

The true impact of CVD in the US

The US holds a major share of the market in North America due to supportive healthcare policies, a high number of patients, and a developed healthcare market. About 647,000 people in the US die from heart disease every year and the cost of heart disease is projected to reach $1.1 trillion by 2035. The US holds a major share of the market in North America due to supportive healthcare policies, a high number of patients, and a developed healthcare market. The trends in the US, however, hold true for the rest of the world as well; atherosclerosis-related diseases represent the plurality, if not the majority, of health-care related costs in the world.

By 2035 45.1% of the US population to have some form of CVD

According to the Centers for Disease Control and Prevention (CDC) Trusted Source, every year, 805,000 Americans have a heart attack, 605,000 of them for the first time. Of those who do have a heart attack, 12 percent will die from it (Thomas, 2020).

Approximately every 40 seconds an American will have a heart attack

Furthermore, it has been reported that 75% of heart attacks occur from atherosclerotic plaque rupture, a key reason why the reversal of plaque formation provides the most effective approach to tackling CVD.

Total annual cost

When accounting for both the direct and indirect costs, it is estimated that the total cost of CVD could reach an astonishing $1.1T by 2035. The cost of care associated with CVD is estimated to be between $214 – $351B, with heart attacks costing $11.5B, making it one of the most expensive conditions treated in US hospitals. These figures perfectly highlight the rising economic impact of CVD, and emphasize the need for a new approach to tackling it.

Individual costs to patients

Further to the overall economic burden, the individual costs to patients are also worth considering demonstrating the burden of CVD.

Cost of a heart attack to a traditional US health insurer

The average cost to traditional health insurers for the first 90 days following a heart attack is $22,034, while Medicare spends over $14,000 per patient on hospital bills in the year after a heart attack (Allen et al., 2022).

Cost of a heart attack to a traditional patient without health insurance

For patients without health insurance, an emergency room visit typically costs $150 -$3,000 or more, depending on the severity of the condition and what diagnostic tests and treatments are performed.

The average length of hospitalization and related costs for heart attack patients is 5.3 days at $21,500 per stay (Pierce, 2022).

Other medical procedures that may be required include:

  • Bypass surgery: ~$70,000-$200,000
  • Corrective heart surgery: ~$30,000-$200,000
  • Treatment with angioplasty and stents; ~$11,000-$41,000

The need for a disease reversal strategy in the current market

The growing financial burden of atherosclerosis and CVD

The financial impact of CVD to both US healthcare and to individuals affected by these conditions has been on a steep rise and as predicted will continue to follow this steep trajectory well into the next decade [Figure 3]. These figures themselves demonstrate that there is space for improvement in the current CVD management strategy.

Chart shows actual or projected total annual cost in US$ billions (Y axis) plotted against cardiovascular disease incidence in various years (X axis)

Figure 3. Projected total costs of cardiovascular disease (CVD), 2015–2030 (in billion USD) in the United States. HBP indicates high blood pressure; CHD, coronary heart disease; and CHF, congestive heart failure. Unpublished data tabulated by the American Heart Association (Duerrschmid , 2015).

In addition, despite the introduction of generics into the market, there is a continuous growth in costs associated with the continued lipid management drug costs [Figure 4]. Further to that, the cost of some generic lipid-lowering drugs that typically have massively reduced overall health costs, have also seen a spike in price. For example, in the year 2013 Pravastatin sodium (10 mg) surged from $27 to $196 for a one-year supply (Jaret, 2015).

Chart shows annual cost in US$ (Y axis) plotted against various lipid management drugs, by year (X axis)

Figure 4. Demonstrating the rise in the price of some common drugs from 2005 to 2013, including a statin, Crestor – the brand name for rosuvastatin. (Jaret, 2015)

Despite the growing $60.9B atherosclerosis drug market, overall costs associated with CVD continue to expand and are quickly becoming independently a significant portion of overall healthcare costs (BioSpace, 2022).

A large proportion of patients remain untreated and undiagnosed

Atherosclerosis may not cause symptoms until an artery is blocked, by which point the person could be having a heart attack or a stroke. When people first present with the first symptoms of atherosclerosis, it may be after significant damage has already occurred [Figure 4].

Figure 5: The progressive nature of atherosclerosis. The accumulation of fatty streaks in the blood vessel wall can begin at an early age, and from then on it progresses. Eventually, it leads to plaque build-up and eventual plaque rupture. Typically, in the early stages, the non-invasive tests including inflammation markers do not show any abnormality and become abnormal only in the late stages of the disease. At this point, the patient could well be experiencing symptoms of exertional angina or even a heart attack. Even the people who are identified as high risk due to risk factors can only benefit from a standard of care that delays the progression. Cyclarity hopes to change this by providing a solution that offers true disease reversal and putting a stop to fatal outcomes.

In the case of atherosclerosis, it is estimated that as many as 42% of adults without known heart disease or symptoms have some degree of atherosclerosis (Bergström et al., 2021). This staggering figure represents an opportunity and a strong market for real preventative therapy – targeting the condition before the accumulation of atherosclerotic plaque reaches critical levels.

The need for a shift from sick care to a health care approach

The typical “sick care” approach that dominates the healthcare system at present, focuses on treating illnesses and is far more costly and time-consuming. A better method of dealing with a population that is getting sicker would be to adopt a true “healthcare” approach, in other words, an approach that focuses on disease prevention. The healthcare system is certainly getting better at ’sick care’ but still lacking in ‘health care’, meaning that today’s healthcare system is keeping people with debilitating age-related disease alive, and for much longer, without addressing the underlying disease. Adopting this approach results in expanding healthcare costs for healthcare systems and patients, before even taking into account the mounting social burden posed by such debilitating conditions.

Although much of the report has focused on the financial gains of introducing a novel disease reversing drug, it is worth considering the personal patient-specific implication of the new approach. The use of statins for example is associated with some adverse effects that some will tolerate less than others. This can lead to issues with medication compliance especially when the sustained benefit provided by statins is reliant on their continual use. Furthermore, experiencing adverse events associated with the late stages of atherosclerosis can be burdensome. Undergoing surgery poses a risk itself and the continued management needed following surgery or the reliance on care, can cause disruptions in the life of both the patient and the family.

A disease reversal drug offers enormous potential to solve the problem

Most will agree that having the ability to prevent the disease and late-stage adverse events is a far more favourable option than simply managing it through treatment. This is even more imperative because the majority of the $1.1T cost of CVD is not due to the lipid management drugs or the blood thinning agents, but rather due to the cost of procedures and long-term management. Furthermore, the cost of atherosclerosis and related CVD continues to grow globally at an alarming, and possibly, an unsustainable rate.

Currently, the cost of statins ranges from $30-$400 per month for generics and $225-$600 for branded statins. However, statins only work if the patient takes them, and in most cases, patients need to stay on them for the rest of their lives. Cyclarity treatment, although more expensive initially, would only need to be taken periodically, perhaps one course every several years. However, the potentially disease-reversing course of treatment would likely eliminate the downstream more costly impact of the disease. With a $60.9B share of the $1.1T being accounted for by drugs that lead to improvement, but do not correct the problem, it suggests that introducing a truly corrective, disease reversal approach, could achieve at least that market share and even more.

Introducing a true disease reversing drug, like Cyclarity’s lead candidate, can supplement and even eventually change the standard of care, without ever needing to directly challenge it. For the time being, we can continue current standard of care strategies with the aim that one day, we will no longer have to rely on them.

Investors may be hesitant to invest in atherosclerosis drugs without real disease-modifying treatments in development, because development of new therapies that provide only incremental advantages over existing SOC may not be sufficient to drive development. First, the time and cost to develop such products are higher, because demonstrating a small incremental improvement over SOC is more difficult in a clinical environment. Second, the market potentials for such incremental drugs are depressed, and clinical success and reimbursement success are riskier.

The time, cost, and success rate associated with getting from lead product identification to the clinic can act as a deterrent to investment. This may seem like a wasted opportunity when one takes into account the substantial burden of diseases such as CVD and potential market size. One aspect that can help to pave a faster route from discovery to implementation is the use of innovative platforms such as those developed by Cyclarity. Cyclarity’s computational platform can help to accelerate translation of complex mechanistic knowledge to new therapies, which have high efficacy, specificity, and safety profile. This approach should raise any potential investors’ confidence in the future success of the company. Furthermore, it has been estimated that for every $1 spent on CVD research, the return on investment is $30 (American Heart Association, 2019).

Despite a significant return on investment, the National Institutes of Health (NIH) invests a highly disproportionate 4% of its budget in heart disease research, a mere 1% in stroke research, and only 1% in other CVDs, investments that are disproportionate to the burden posed by those diseases (American Heart Association, 2019). This could well be a reflection of the lack of new treatments that could successfully outperform the current treatments available.

Novel disease modifying approaches represent the solution to that investment dilemma. In addition, with an area of great medical need and one which poses a large economic burden, it presents an exciting opportunity for investors.

Technical Risk

One of the main challenges to overcome, when introducing a new treatment strategy that works on previously untargeted pathways, is the need for novel diagnostics. Identifying novel diagnostic factors is of importance for both the initial identification of the target group and also to identify a suitable endpoint and for the monitoring of the efficacy of treatment.

At present, doctors rely on lipid panels to assess patients’ risk of CVD and to prescribe cholesterol-lowering drugs such as statins, or by using imaging techniques to assess individual risk in combination with the assessment of individual risk factors. However, these tests come with limitations. Lipid panels have been shown to correctly identify 40% of people at risk for CVD, and the extent of CVD largely varies for individuals with the same cholesterol levels as shown by these tests. With regards to Cyclarity’s approach, these tests do not quantify the toxic cholesterol which Cyclarity is targeting through its disease modification approach. Cardiovascular imaging techniques could be an alternative option to assess the amount of plaque in arterial walls, however, they are not universally available, are costly, require highly trained personnel, and the extent of atherosclerosis can substantially vary between individuals in the same traditional risk category. Therefore, there is a need for developing alternative rapid and non-invasive methods to estimate the atherosclerosis burden and the effectiveness of any interventions.

An ideal biomarker would likely be a plasma-based biomarker that is directly related to the effects of Cyclarity’s drug, whether measuring the byproduct of clearance of plaque or otherwise. This type of diagnostic marker addresses any limitations of imaging approaches and improves the precision of monitoring drug effectiveness.

Market risk

The first statin medication was approved in 1987, and since then, statins have remained the main standard management of atherosclerosis and those at risk of CVD. Since their adoption, no therapies have been seen to be “good enough” to replace statins or challenge the current standard of care.

Despite their wide use, the risk reduction achieved by taking statins is lower than one might first assume, and this has been well documented by a recent meta-analysis which has also highlighted a large heterogeneity among the different studies (Byrne et al., 2022).

Similarly, a study published in the journal Heart BMJ, also found that half of the patients prescribed statins in primary care fail to reach ‘healthy’ cholesterol levels after two years of treatment with these drugs (Akyea et al., 2019).

Modification of lifestyle factors, including smoking cessation and exercise, as well as the use of BP-lowering medication, have led to a decrease in CVD mortality, although atherosclerosis remains the world’s biggest killer (Bhatnagar et al., 2016). The rising prevalence of the condition also means there are more people with atherosclerosis, and, therefore, the number of people experiencing adverse events also rises. Even though lifestyle modification and drugs can reduce and delay these adverse effects, the condition still poses a big impact on the quality of life of patients. This highlights the need for new treatment strategies that combat both morbidity and mortality, helping patients achieve an improved lifespan as well as healthspan.

With all this in mind, it may be the case that these recent findings could create a perfect time for a new therapeutic approach to entering the market from a market risk perspective – even more so, one which can target the root cause and provide a true disease modification rather than simply disease-delaying.

Nonetheless, Cyclarity will be launching into a market still driven by cholesterol mediators without competing drugs that can modify the disease state. If that is the case, the expectation is that the market will also still be heavily reliant on invasive, post-event treatments for the amelioration of the effects of heart attack and stroke.

Market adoption

The question remains – are we ready for a new type of treatment or are statins far too deep-rooted for new medication to infiltrate the current standard of care?

Given that the market has not seen any breakthroughs and the level of effectiveness of current treatments could be improved, this suggests that a new approach is needed. This is just one of the reasons why Cyclarity’s solution will constructively disrupt the market. Although, the best initial approach for Cyclarity’s may be to complement the current standard of care rather than aiming to replace it from the get-go.

Cost is often a major consideration when choosing drugs for mainline treatment. Therefore, the cost-effectiveness of any new non-statin therapy will play a role in determining its uptake into clinical practice. The key to a revolution in the standard of care will be a product that can more significantly stall or reverse the course of the disease, and the market economics challenge will be immediately solved by any drug which can successfully succeed in that. Cyclarity has the only approach poised to do that over the next decade.

Cyclarity’s approach to true disease medication, and therefore reversal of age-related disease, without doubt, offers a great deal of promise for investors, for healthcare systems in the US and globally, and most of all for those affected by atherosclerosis-related disease.

As the need for new therapeutic approaches becomes increasingly apparent, this may be the perfect opportunity for Cyclarity to enter the field, as it is one of the few solutions available that addresses the limiting factors of previous therapies both from a scientific perspective and from a market perspective.

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