Adele Graham-King, Contributing Editor11.17.15
It’s a rare occurrence these days for the Pharma industry to introduce a new class of drugs. In fact, searching hard to find new classes of drugs that have been discovered I can only find three other new class announcements in recent years—one anti-malarial, another semi-synthetic antibiotic and lastly one to treat hepatitis C virus. But the announcement of the discovery of a new class of drugs in clinical research to actually achieving approval for market is a whole different ball game.
However, in July and August the FDA approved not one, but two new drugs in a new class licensed to treat hypercholesterolaemia. A move that could potentially make a ground-breaking difference in the treatment of a potentially fatal condition.
Hypercholesterolaemia is a condition that has seen a huge change in mortality and morbidity over the past 30 years. Identified by blood tests that measure cholesterol levels the risks associated with uncontrolled raised lipids include an increased risk of cardiovascular disease including coronary artery disease (CAD), cerebrovascular disease and peripheral vascular disease (PVD).
One of the issues associated the hyperlipidaemia is that it is a silent disease and although there are certain characteristics such as xanthelasma palpebrarum, which are yellowish patches consisting of cholesterol deposits above the eyelid more commonly observed with familial hypercholesterolaemia, it is only detectable with clinical investigation.
Although the condition has been recognized for many years it was historically difficult to treat and the pharmacological agents weren’t exactly great for patient adherence. Indeed as many sufferers of primary hypercholesterolaemia are young children and adults, medications needed to be easy to take which hasn’t always been the case, leading to poor disease management impacting on morbidity and mortality.
Historically this condition was treated with cholestyramine powders; although now almost redundant in this area of treatment this bile acid sequestrant was effective in converting cholesterol into bile acids, which were excreted from the body effectively. Presented as a powder and taken mixed into water these powders weren’t the best to take!
However, the arrival of statins to the market in the mid 1990s started by the launch of Mercks’ Zocor (simvastatin) fundamentally changed the way in which hyperlipidaemia was treated globally. Statins, also known as HMG-CoA reductase inhibitors inhibit the enzyme HMG-CoA reductase, which is required in the cholesterol production pathway. Inhibiting this enzyme can have a dramatic effect on blood levels of cholesterol and supported with strong clinical evidence they are used routinely in primary and secondary prevention of CVD. Furthermore statins are effective in lowering cholesterol in children with primary hyperlipidaemia and much more favorable to take than the dreaded powders of the 1980s. Although there are associated side effects, the benefits generally outweigh the negatives and as there are plenty of options on the market a suitable statin can usually be found for most patients. With the expiration of several patents in the statin market place their use has become the main stay in treating high cholesterol.
But the truth is that statins alone are not always the answer to this problem and although dietary modification and exercise are ‘prescribed’ as part of disease management this doesn’t always happen. Even strict adherence to medication alongside a healthy lifestyle doesn’t always result in the desired reduction in lipids and therapeutic levels simply aren’t achieved. This is a scenario particularly is seen more commonly in primary hypercholesterolaemia. So what do to?
It is possible to take adjunct therapy of statins with ezetimibe (Zetia) which is a cholesterol re-uptake inhibitor and this may be taken alongside fibrates but fortunately there has been ongoing research and development in order to create other, more efficacious drugs for this difficult to manage group of patients.
A long time in their creation, Pharma have turned to monoclonal antibodies in order to look for a solution to the problem. Monoclonal antibodies, which in lay man’s terms are laboratory produced molecules that can attach to cells in order to make them more identifiable to our own immune system, thus resulting in opening cells to immune attack or altering their ability to work as they are programmed to do. Much more commonly recognized up to now in the treatment of certain cancer the can be a useful and effective tool for disease management.
In July and August 2015 the FDA approved to new monoclonal antibody drugs for use in the treatment of hypercholesterolaemia. Evolocumab (Repatha) and alirocumab (Praluent) are both human monoclonal antibodies, which inhibit protein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein, which stops the liver from acting on LDL-C (Low Density Lipoprotein) allowing cholesterol to stay elevated in the blood. The two new compounds are both PCSK9 Inhibitors which effectively interfere with the PCSK9 protein by binding to it, rendering it to be ineffective in binding to the LDL receptors which allows the liver to be much more efficient in metabolizing cholesterol.
Backed up by a whole ruck of clinical trials which were reviewed and recently published in the Annals of Internal medicine the PCSK9 Inhibitors are thought to lower LDL Cholesterol by almost half (47%) on average. This has the potential to have a massive impact on the morbidity of patients suffering from this disease. Although the current clinical evidence has shown that the new drugs are highly efficacious this doesn’t extend to making people live longer however it does seem that there is a reduced risk of MI or cardiovascular death. A large global clinical trial is currently underway to examine further the potential impact that treatment with PCSK9 Inhibitors will have on hypercholesterolaemia. Due to report in 2017 this will potentially provide the evidence that these new drugs will extend life.
Both evolocumab and alirocumab are delivered by injection, which in itself is a change in the way that hyperlipidaemia is managed and some patients will not want to go down this route of treatment. However due to the fact that both these medications are only indicated to be used in conjunction with maximum statin therapy, diet control and exercise in those who are resistant to statins or people who have primary hypercholesterolaemia and not responding, these are people who are at high risk of further, more serious events and therefore must be a consideration. Importantly both companies are aiming to make the drugs financially affordable, certainly in the US, which will potentially create an extensive pool of patients looking to try the new cholesterol blasters.
In 2008 atorvastatin was reported to be worth in the region of $12.4 million and the statin market as a whole several years earlier was reported to be worth $18.7 billion. Surely this market has the potential to reach the same dizzy heights for the Pharma companies, as well as a huge impact on patients who up until now have been unable to achieve effective therapeutic management of a life threatening condition. With the end of the clinical trial in sight in 2017 the results could see a shift in the management and life expectancy of these patients. This new category of drugs could very soon create a new era in the survivability of hypercholesterolaemia.
Adele Graham-King
Contributing Editor
Adele is a design consultant who works in prod- uct development for medical and healthcare ap- plications. Her background is in pharma, and she has a degree in applied physiology.
However, in July and August the FDA approved not one, but two new drugs in a new class licensed to treat hypercholesterolaemia. A move that could potentially make a ground-breaking difference in the treatment of a potentially fatal condition.
Hypercholesterolaemia is a condition that has seen a huge change in mortality and morbidity over the past 30 years. Identified by blood tests that measure cholesterol levels the risks associated with uncontrolled raised lipids include an increased risk of cardiovascular disease including coronary artery disease (CAD), cerebrovascular disease and peripheral vascular disease (PVD).
One of the issues associated the hyperlipidaemia is that it is a silent disease and although there are certain characteristics such as xanthelasma palpebrarum, which are yellowish patches consisting of cholesterol deposits above the eyelid more commonly observed with familial hypercholesterolaemia, it is only detectable with clinical investigation.
Although the condition has been recognized for many years it was historically difficult to treat and the pharmacological agents weren’t exactly great for patient adherence. Indeed as many sufferers of primary hypercholesterolaemia are young children and adults, medications needed to be easy to take which hasn’t always been the case, leading to poor disease management impacting on morbidity and mortality.
Historically this condition was treated with cholestyramine powders; although now almost redundant in this area of treatment this bile acid sequestrant was effective in converting cholesterol into bile acids, which were excreted from the body effectively. Presented as a powder and taken mixed into water these powders weren’t the best to take!
However, the arrival of statins to the market in the mid 1990s started by the launch of Mercks’ Zocor (simvastatin) fundamentally changed the way in which hyperlipidaemia was treated globally. Statins, also known as HMG-CoA reductase inhibitors inhibit the enzyme HMG-CoA reductase, which is required in the cholesterol production pathway. Inhibiting this enzyme can have a dramatic effect on blood levels of cholesterol and supported with strong clinical evidence they are used routinely in primary and secondary prevention of CVD. Furthermore statins are effective in lowering cholesterol in children with primary hyperlipidaemia and much more favorable to take than the dreaded powders of the 1980s. Although there are associated side effects, the benefits generally outweigh the negatives and as there are plenty of options on the market a suitable statin can usually be found for most patients. With the expiration of several patents in the statin market place their use has become the main stay in treating high cholesterol.
But the truth is that statins alone are not always the answer to this problem and although dietary modification and exercise are ‘prescribed’ as part of disease management this doesn’t always happen. Even strict adherence to medication alongside a healthy lifestyle doesn’t always result in the desired reduction in lipids and therapeutic levels simply aren’t achieved. This is a scenario particularly is seen more commonly in primary hypercholesterolaemia. So what do to?
It is possible to take adjunct therapy of statins with ezetimibe (Zetia) which is a cholesterol re-uptake inhibitor and this may be taken alongside fibrates but fortunately there has been ongoing research and development in order to create other, more efficacious drugs for this difficult to manage group of patients.
A long time in their creation, Pharma have turned to monoclonal antibodies in order to look for a solution to the problem. Monoclonal antibodies, which in lay man’s terms are laboratory produced molecules that can attach to cells in order to make them more identifiable to our own immune system, thus resulting in opening cells to immune attack or altering their ability to work as they are programmed to do. Much more commonly recognized up to now in the treatment of certain cancer the can be a useful and effective tool for disease management.
In July and August 2015 the FDA approved to new monoclonal antibody drugs for use in the treatment of hypercholesterolaemia. Evolocumab (Repatha) and alirocumab (Praluent) are both human monoclonal antibodies, which inhibit protein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein, which stops the liver from acting on LDL-C (Low Density Lipoprotein) allowing cholesterol to stay elevated in the blood. The two new compounds are both PCSK9 Inhibitors which effectively interfere with the PCSK9 protein by binding to it, rendering it to be ineffective in binding to the LDL receptors which allows the liver to be much more efficient in metabolizing cholesterol.
Backed up by a whole ruck of clinical trials which were reviewed and recently published in the Annals of Internal medicine the PCSK9 Inhibitors are thought to lower LDL Cholesterol by almost half (47%) on average. This has the potential to have a massive impact on the morbidity of patients suffering from this disease. Although the current clinical evidence has shown that the new drugs are highly efficacious this doesn’t extend to making people live longer however it does seem that there is a reduced risk of MI or cardiovascular death. A large global clinical trial is currently underway to examine further the potential impact that treatment with PCSK9 Inhibitors will have on hypercholesterolaemia. Due to report in 2017 this will potentially provide the evidence that these new drugs will extend life.
Both evolocumab and alirocumab are delivered by injection, which in itself is a change in the way that hyperlipidaemia is managed and some patients will not want to go down this route of treatment. However due to the fact that both these medications are only indicated to be used in conjunction with maximum statin therapy, diet control and exercise in those who are resistant to statins or people who have primary hypercholesterolaemia and not responding, these are people who are at high risk of further, more serious events and therefore must be a consideration. Importantly both companies are aiming to make the drugs financially affordable, certainly in the US, which will potentially create an extensive pool of patients looking to try the new cholesterol blasters.
In 2008 atorvastatin was reported to be worth in the region of $12.4 million and the statin market as a whole several years earlier was reported to be worth $18.7 billion. Surely this market has the potential to reach the same dizzy heights for the Pharma companies, as well as a huge impact on patients who up until now have been unable to achieve effective therapeutic management of a life threatening condition. With the end of the clinical trial in sight in 2017 the results could see a shift in the management and life expectancy of these patients. This new category of drugs could very soon create a new era in the survivability of hypercholesterolaemia.
Adele Graham-King
Contributing Editor
Adele is a design consultant who works in prod- uct development for medical and healthcare ap- plications. Her background is in pharma, and she has a degree in applied physiology.