In the previous entry we discussed the many types of companies that get interested in rare diseases, each of them because of different reasons. If your disease field matches one of those business propositions you will get at the top of the list of interesting diseases for that company, but another part of the decision equation is time, or field maturity. Is this field ready for us to start working on it already?
The following are the questions that a company will often need to answer to be able to judge if the field is ready for them, too early for them, or maybe even too mature for them to get in. Some of it applies to both large and rare diseases while some of the questions are more important for rare diseases.
If you work at a rare disease patient organization or research foundation, make sure you also ask yourself these questions:
o How many patients are out there? Some companies will be interested in diseases with as little as 500 patients, but others might have a cut off of 3,000-5,000 treatable patients. If the numbers are not known, or if they are too small, the probability of getting a company interested will be much much smaller.
o Is there already a drug approved that treats this disease in a satisfactory way? If a company can be the first-to-market it will be more interested in the disease.
o Who else is developing drugs for this same rare disease? The larger rare diseases might support competition, with multiple companies hoping to get a piece of the market, but if the disease is very rare one of the main drivers of companies to choose a rare disease, which is avoiding competition, will not make sense anymore.
o Do we know the cause of the disease and what is affected? This will help them see if your disease is a good match for their drug or technology, and even to see if they might have already have some already developed drug that could help your disease because it acts on the same signaling pathway.
o Are there good animal models of the diseases? Generally this is a mouse model. If there are good mouse models the company could either quickly test their drug to see if it has efficacy (if the drug already exists), or use it to confirm the efficacy of a future drug that they might want to develop. If there is no mouse model yet, some companies might worry that the disease might turn out to not be easy to model in a mouse, and that will make it harder to validate their drug in a relevant model prior to clinical trials. In some diseases, other animals are used to model the disease. What matters is if there is a good animal model that has symptoms in common with the patients or not, and if the company can have access to it.
o Are there other preclinical models available? The good mouse model is the bare minimum, for many research programs they will need to have access to DNA carrying the mutation and to cell cultures from patients.
o Is the patient population homogenous? Is there well-documented natural history? This is important to know which are the symptoms that need to be treated and to reduce patient variability. Patient variability is one of the problems of larger common diseases, and the reason of many trials failures. Therefore having patients that are very homogenous (diseases caused by one gene, for example) is a major attractive point of rare diseases.
o Could we find clinical centers willing to run clinical trials and patients willing to enrol? If there are too few specialists or they are not confident that they could find patients, companies will wait for the field to be ready.
o Would we know how to design a clinical trial? Depending on the disease symptoms it might be easy or not to know what could be measured during clinical trials to investigate drug efficacy. Not having a clear symptom to measure in a trial, what is generally called “an endpoint”, can be a major cause of clinical trial failure.
o Is there any previous case of regulatory agreement or approval? If the regulatory authorities (generally FDA or EMA) have already agreed with another company which endpoints are good, and how many patients are needed, and confirmed that they consider that rare disease a legitimate separate disease, then a lot of the regulatory risk has been lifted and more companies will be interested.
Because it takes time to be able to answer all of these questions in an affirmative way, some of the most recently described rare diseases will not be mature enough for companies to work on them. The next entry of the Impatient Series will address how, from a patient organization, you can advance research in your disease to the point and make it mature.
Let’s start an #ImpatientRevolution!
Ana Mingorance, PhD