Cross-functional and pre-competitive consortia are emerging as a way to navigate the gridlock and identify novel therapies.  

There is a sense of urgency, primarily driven by patient advocacy groups, to identify new therapies, and improve on existing therapies aimed at the rare diseases their loved ones suffer from.  

Traditionally the process has involved sponsorship of academic labs that may work unilaterally or within a small network to identify potential candidates. Communication within these networks has been a challenge and once a promising compound has been identified, progress has typically been slow on intellectual property (IP), so access to results and the input from outside the network has been limited.   This has limited the extent to which a compound can be tested and profiled. Very often these compounds have eventually progressed to clinical stages without in-depth knowledge of either the mechanism of action or a complete pharmacokinetic profile. Given the funding constraints as well as the added hurdle of coordination and communication, is it any wonder that this incomplete drug discovery process takes less time than a traditional step-wise drug discovery path, but more often ends in a clinical failure?

With the advent of new FDA regulations for rare and orphan diseases the conventional drug discovery and development route is now a relatively truncated route but issues of safety and non-clinical efficacy are still paramount. The long and winding road that has traditionally started with target identification and subsequent lead candidate identification, then the progresses to optimization, preclinical pharmacology and safety studies is not a path that need be adhered to exactly to the letter.

Yet while this approach may help maximize clinical success and build a stronger safety profile, it can take several years to accomplish—precious time that many of these extremely ill patients do not have.

What is required is to find a middle ground between conventional drug discovery and fast track drug discovery. The key to this comes through true commitment and open collaborations with data sharing, best practices emulation, imagination, creativity and open dialogue between clinicians, researchers, patient groups and regulatory agencies.

A recent symposium in New York City, organized by Charles River Laboratories, addressed the critical need for collaborations that will accelerate successful rare disease drug discovery. Speakers with expertise in various disease areas (Duchenne’s muscular dystrophy, Batten disease, academia’s, and amyotrophic lateral sclerosis (ALS)) came together to discuss challenges and best practices in collaborative drug discovery.

One of the strongest impediments for rare disease drug discovery, for instance, revolves around the issue of IP.  Certain institutions may move slowly on IP management, which delays compound testing by pharmaceutical and biotech or even other academic labs. The tendency, in the past, has been to be less open about sharing data due to the pressure in academic culture to “publish or perish”.

The formation of cross-functional and pre-competitive consortia is emerging as a way to navigate the gridlock and identify novel therapies as well as repurpose and reposition therapies aimed at other indications. Current consortia have a mixed success rate, running the gamut from clinical success to absolute inertia. Panel discussions during the symposia focused on best practices that may help make consortia successful. Interestingly, the scientific hypotheses for the disease under investigation is rarely a problem and in the last few years, for many diseases, better funding has become more readily available. More often, softer skills such as good project management, strong leadership, clear communication, access to data from a wider range of sources and strength of purpose at every level within the consortium are essential for success.

The inclusion of contract research organizations (CROs) in the drug discovery ecosystem has often times been an afterthought because in general CROs have typically worked in a fee-for-service fashion. However, there is an increasing shift towards true partnership and active collaboration with scientifically sound and innovative CROs. CRO’s, like Charles River, who have engaged in drug discovery for some time have the experience and knowledge to identify critical milestones and the data that needs to be generated to move a compound or therapy to the next phase of drug development.

The complex ecosystem includes academic labs that perform innovative research to identify disease drivers and targets for rare diseases, and pharma/biotech companies that have the resources to complete the preclinical and clinical trials and navigate the regulatory process. Regulatory agencies are also an integral part of the ecosystem and they can be true collaborators if involved early in the drug discovery process as they can share IND-filing requirements with investigators to help fast-track novel therapies. One of the speakers at the symposium illustrated this point by showing how gene therapy delivered via an adeno-associated virus is being used to treat Batten disease (CLN6 variant) in children.

Managing this complicated ecosystem can be challenging. Multiple components require careful attention, including regular communication with patients and advocacy groups, preclinical investigators, clinical trial groups, regulatory agencies and funding agencies. But it is possible! Successful groups such as CHDI, which is seeking solutions for Huntington’s disease or Target ALS, are evidence that this model is working and, in fact, gaining momentum.

With adequate funding and successful management of foundations and consortia as well as the valuable input from the right CRO we can begin to see a horizon whereby we may finally be on the road to moving some of these rare diseases to the solved column.

How to Cite:

Venkateswaran, Anjli. Hitting Home Runs for Rare Diseases. Eureka blog. Nov. 9, 2016. Available: