Orphan Drugs - Precision Medicine Initiative

The Continuing Journey from Orphan Drugs to Precision Medicine: The Rise of “Causality Drugs”

In Clinical Development, Regulation & Government by Freya Smale

I have said it before, and I will say it again – if every drug is an orphan drug, none of them are.

Today, as the White House announces a series of commitments from various stakeholders in the pharmaceutical industry towards advancing precision medicine, one thing is becoming abundantly clear – the time where an orphan drug indication means anything might be coming to an end.

That is not to say that they will not exist. Indeed, many have emphasized that the growth of Precision Medicine by no means has indicated that anyone is looking to repeal the Orphan Drug Act or any incentives towards rare diseases.

Rather, it is to say that if this new paradigm does indeed come to pass, then there will soon come a time where every drug is an orphan drug, and the vestigial incentives gained from having an orphan indication will no longer serve an advantage in a market filled with drugs exclusively for rare, “precision” diseases.


Part of the announcements today include the NIH’s PMI Cohort program. This is meant to be a 1 million person strong database of sequenced genomes and biological data with which industry, academia and government can collaborate to understand further the natural history of diseases and how to conquer them. They are working with Google’s Verily and Vanderbilt University to accomplish this.

This approach should be a very familiar pattern to companies engaged in Rare Disease research. Using patient groups and patient registries to develop a natural history – if not a genomic analysis – of disease is a vital component when researching an orphan designated drug which have to treat specific genotypes.

In essence, what this means is that the NIH has commissioned a very large patient registry – but not for any specific disease. Rather, they are looking to enable this data to be used to further understand every disease, even those that people wouldn’t consider “orphan”.

This is exciting not in the execution, but in its implications. In order to achieve precision medicine, the industry must acknowledge that genomic (and proteomic) data must be used from the very beginning of the drug development process.

But using genomic data by its very nature is going to categorize individuals into subsets, both phenotypically and genotypically. This is going to result in a shift in focus. No longer will “blockbuster” drugs be the ones that can treat as many people as possible with disregard to the mechanism of achieving the outcome. Rather, a blockbuster drug will be one that could potentially hit as many of the genotypic subsets of the disease as possible, or hit one subset so well that you effectively cure the disease.


The biggest gap in achieving precision medicine is still the transfer of genomic data to the bench work upstream in the drug development process.

While daily, it seems there are new health technology innovations by IBM, Apple, Google, Microsoft and others, there are far less examples of this data being used outside of the clinician-patient interface. This is a major reason why cell and gene therapy research companies have been invited to the World Precision Medicine Congress USA 2016, launching in Washington D.C. this November. Their role in the conversation is equally if not more important than allowing a patient to understand their genotype.

These technologies are an important and enabling facet of bringing the healthcare providers towards the paradigm by driving the family physician to think in genetic terms. However, a physician understanding an individual’s genotype does little to solve an issue if the drug development has not kept pace. Diagnosing a patient with a subtype of a diseases based on their genetic or proteomic analysis is fantastic for keeping data and information, but is useless if there is no subsequent treatment based on that information.

This is where the work that has been put into Orphan Drugs will become increasingly valuable. Many orphan drug companies, by nature of the diseases they are curing, have put millions of research dollars into understanding the genetics and subsequent pathways that cause their diseases, and treat based on cell or gene therapies (or large molecules) that can impact those specific pathways. Often these companies work with patient groups formed for the specific diseases.

This is where the NIH’s program is so powerful. By essentially crowdsourcing the genomic work, they are lifting a burden off of the pharmaceutical industry do that they can begin analyzing and utilizing this data as they expand their pipelines.


What the NIH has done is enabled the industry to take the learnings of years of ODA incentivized research and grow beyond the scope of “rare diseases”. To grow beyond a binary “rare/common” paradigm into one where every subset of every disease is treated as the unique genetic trait that it is.

To grow beyond trying to simplify, and instead drive towards complexity.

Indeed, a more apt title moving forward would be “Causality Drugs”. Old-school blockbusters such as acetaminophen were driven not by complexity, but by simplicity. It looked not at a cause, but rather an effect, and how to mitigate it for the longest period of time in the most people.

Causality drugs emphasize treating a specific cause in a way that can only be enabled by the omics revolution – hitting on a specific oncogene, silencing a specific mutation. By moving towards causality, we can drive not just treatments, but cures.

As we understand rare diseases in their current state, the number of people with the disease must fall below a certain number. I believe that very soon, if President Obama gets his wish, even that number will seem far too high as the new paradigm takes hold.

World precision medicine congress usa 2016