– Dr. Harsha K Rajasimha
The use of a patient’s or tumor’s DNA sequence to diagnose/characterize a disease and select or discover drugs that have the highest likelihood of response with least toxicity is one way of broadly defining Precision Medicine. Although most doctors would agree that medicine is far from precise, President Obama’s state of the union address in early 2015 made ‘precision medicine’ a household phrase drawing public attention to this burgeoning field. Mayo clinic has adopted the phrase individualized medicine in naming its world class center at Rochester, MN. Some even refer to it as genomic medicine but I like ‘personalized medicine’ (PM) better. Major healthcare organizations in US and around the world are early adopters and are already practicing PM.
In the biopharmaceutical industry, more drugs are receiving orphan drug status and priority review by FDA than ever. In 2014, records were shattered with an astounding 467 orphan drug designation requests received by FDA (~35% increase over 2013), an astonishing 293 orphan drug designations granted (~13% increase over 2013), and a whopping 49 orphan drug approvals (~53% increase over 2013). This amazing output for FDA’s orphan drugs program is not an exception but rather a trend (even more orphan drug designation requests have been received in 2015 already) giving us a glimpse at the future of drug development. This trend is likely linked to the greater use of genomics for biomarker discovery and for stratifying patients during clinical trials.
If we look at the list of all FDA Approved Orphan Drugs between 1983-present, a number of them are of course targeting rare diseases but one can also note that a large number of these approvals and designations are for certain rare types of more common diseases such as Cancer. Today, we know that there are over 200 types of Cancer. A growing number of Cancer drugs are falling into orphan drug category which is no surprise as the Oncology community is now several years into tumor genetic profiling using genotyping or multi-gene panels. There are multiple success stories of targeted cancer therapies receiving orphan drug status and approvals on expedited basis such as Xalkori (for ALK+, ROS+, or Met+, NSCLC), Iressa (for EGFR+ NSCLC), etc. You also find this list of approved orphan drugs targeting a range of diseases such as Repatha for familial hypercholesterolemia, Orkambi for Cystic fibrosis, Duadopa for late stage Parkinson’s, Eloctate for hemophilia A, among others.
What’s more striking is that the beginning of PM is marking the end of ‘one-size-fits-all medicine’ as drugs that failed earlier trials are being repurposed with a better stratification strategy and targeting smaller sub-populations. Biopharma companies are no longer relying solely on hitting those blockbuster drugs but rather going after a large number of orphan drugs with associated companion diagnostics. Which means many common diseases are getting broken down into a number of rare diseases (sub-types) with drugs targeting specific sub-types. A divide and conquer approach seems to be emerging to divide the complex common diseases into a number of more tractable rare diseases.
No wonder, the global genes project is now reporting over 7000 rare diseases with new diseases being added to the list daily. So taken together, the beginning of Precision Medicine to me, marks the beginning of the end of common diseases… its the beginning of an era of rapid discovery of more rare diseases and orphan drugs… a necessary breakthrough to overcome some of the challenges of common diseases.