The war on cholesterol continues unabated with the new star target (PCSK9) having been the subject of a hotly contested race in the clinic over recent years, but now, perhaps inevitably, that drug development contest looks like it's going to be further contested - in a courtroom - before a single dollar has been made by anybody.
To many it appeared that the war on cholesterol and the cholesterol (drug) wars were already far behind us, following the phenomenal success of the game-changing drug class known as statins - a class which achieved the panacea (nirvana?!) of unquestionably benefiting people's lives and health while simultaneously raking in billions of dollars to their manufacturers - eventually making them the most successful drugs in history.
However, while they have been spectacularly successful, not everyone responds well to statins and there are some fairly serious side effects which affect patient compliance, so the door was never entirely slammed shut. Or, looking at it the other way, the spectacular success of statins and the riches they brought in were sure to keep pharmaceutically-minded researchers on the hunt for the next HMG-CoA Reductase, which is the target against which statins were discovered.
That dream became reality with the discovery of the PCSK9 class; PCSK9 is a proprotein convertase that binds to the LDL receptor and targets it's complex with cholesterol for degradation, thereby reducing receptor quantity at the cell surface. This can lead to reduced cholesterol uptake which is an identified trigger for cardiovascular disease leading to heart attacks and strokes. A lot of hope for this new target crystallised into drug candidate reality when preclinical studies underlined that PCSK9 was a tractable target that did indeed lower cholesterol levels when inhibited.
Two of the players who are ahead in the race to market a PCSK9-targeting biologic are Sanofi/Regeneron and Amgen; pharmaceutical companies that have each completed Phase III clinical trials and have applied to the FDA for approval to market their drug candidates. It's a neck-and-neck race and the pressure mounted on Amgen with the announcement by Sanofi and Regeneron this summer that they were intending to use an extremely valuable FDA (rare pediatric disease) priority review voucher in connection with the Biologics License Application (BLA) submission for their Alirocumab.
These priority review vouchers are worth their weight in gold to drug companies because they save time, and time is big, big money in the pharmaceutical world. Even if it simply means that you get to market six months earlier than your nearest competitor, that can make a massive difference to roll-out sales and early adoption by the medical community and patient segment. No doubt this has played a part in the recent issuance by Amgen of a lawsuit claiming that Sanofi-Regeneron are infringing on Amgen patents (# 8,563,698, 8,829,165, and 8,859,741) which detail and claim monoclonal antibodies to PCSK9. Amgen's own Evolocumab is the subject of another BLA tabled at the FDA, and they aren't going to take the possiblity of being second sitting down.
Amgen wants an injunction to prevent the manufacture, use and sale of Sanofi and Regeneron's Alirocumab, so this is serious business - for both parties. In any case, statins have not disappeared, and they are still big business themselves, so it is not likely that PCSK9 therapeutics will dominate the market anytime soon. In fact, analysts think it will be a rather slow roll-out, with PCSK9 inhibitors used in only a selected subset of those at risk of cardiovascular disease, with a more global adoption only likely after a trouble-free introductory period.
Why change something that's working well, will be the argument for many practioners and patients alike, and if you are on a statin with no side effects experienced, then I can see the point. But it is tempting to consider that with the doses perfected over time, the combination of a low dose statin with a to-be-determined safe dose of a PCSK9 inhibitor could be the magic bullet and might eradicate heart disease for the majority.
We are not there yet, of course, and there is an important aside to that potentially attractive proposition in that it will only further contribute to the burgeoning population vulnerable to and suffering from age-related CNS disease. This is going to reach a pandemic-type scenario by 2050 and the lack of pharmacueutical success in this disease class is of real concern to us all - old and young alike. We are almost all either heading towards the vulnerable age group, or have loved ones living in that age group, and the abject lack of any transformative therapeutic for Alzheimer's disease, dementia more generally, Parkinson's disease etc. is (going to be) a major problem for society.
The prevalence of CNS disease is a symptom of medical success in other key conditions that used to be a death sentence, and now we need to be focusing on some of these diseases that we are all going to face in one capacity or another in our lifetimes. The cost to the healthcare system of age-related CNS disease is a staggering one, and one which is exponentially rising; investing some of the future costs into higher priority research today is going to be essential in making any progress.
The pharmaceutical companies who have raked in billions on statins or those about to on PCSK9 inhibitors could do well to reinvest in age-related disease areas that those drugs help us live to see. While that is perhaps an apparently ungrateful way of looking at it, pharmaceutical companies can (must) be persuaded to reignite their interest in the currently "unpopular" CNS disease segment, especially given that it will represent a massive market by 2050 and such companies don't have any problem printing money when they get it right.
But, if they get to print their money, and we get to finally have a transformative, disease-modifying CNS disease therapeutic, well, that's a big win-win and I think we can all live with that. In the meantime, we can all focus on developing better PCSK9 inhibitors and that does include us, because AmorChem has a small molecule PCSK9 program in our own portfolio!
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