March 12-14, 2014
Designing innovative therapies for neuropathic pain: preclinical and early clinical development challenges
The second scientific meeting of the Foundation for Peripheral Neuropathy was successful in bringing together basic and clinical scientists from academia, NIH, and industry to identify the challenges in Preclinical and Early Clinical Drug Development for Neuropathic Pain. The meeting focused on preclinical drug development approaches and challenges in Phase II trials for neuropathic pain. In the preclinical stage, advantages and disadvantages of phenotypic and candidate molecular target based screens were discussed along with the new role academic drug discovery centers are playing in early drug discovery. These are outlined in three articles by Drs. Slusher, Enna and Inglese. After outlining some of the potential new drugs for neuropathic pain, four industry experts led a roundtable discussion on industry’s perspective on developing drugs for neuropathic pain. The second half of the meeting focused on challenges in Phase II trials of neuropathic pain. Several issues were identified.
- Discrepancy in defining peripheral neuropathy as either a disease or syndrome.
- Inclusion/exclusion criteria in studies have not been standardized. Among the factors related to this issue are confounding disorders, concomitant medication usage, and identifying representative patient populations.
- Outcome measures with respect to pain intensity have not been clearly defined and are difficult to quantify.
- The placebo effect plays a significant role in studies and impacts data analysis (Variation in response: 20-70%).
- Resource limitations due to funding and the changing landscape of the research field.
- Data sharing: confidentiality versus open access.
Discussions at the meeting led to the recognition that at the preclinical stage there will be room for both phenotypic and mechanism-based screening approaches, with a greater involvement of academic drug discovery centers than we have experienced in the past. Partnerships between academia and industry will align the academic scientists’ expertise in disease and animal models with the drug discovery expertise of academic centers and industry and will likely result in faster identification of candidate drugs.
On the clinical end, there is an urgent need to develop resources for biomarker discovery and infrastructure for academic clinical trials. The Peripheral Neuropathy Patient Registry (PNRR), funded by the Foundation for Peripheral Neuropathy is such a resource.
The rationale and aims of the PNRR:
- Stored biological samples collected throughout the course of PNRR in a central repository that will be accessible to any scientist with promising biomarker leads for the purposes of verifying initial results and assessing correlations to clinical outcomes and other biomarkers
- Identify phenotypic clinical features of patients with neuropathic pain
- Improve and/or assist with clinical trial recruitment process
- Develop a comprehensive and uniformly acquired clinical dataset with correlated biological samples that can be used in biomarker verification studies
- Establish standardized protocols for acquisition, transfer and analysis of clinical data and biological samples that can be used by the research community
- Create standardized data protocols to ensure that tests and assessments conducted at multiple sites and across multiple cohorts can be pooled and shared in the clinical community
- Establish a comprehensive set of clinical biospecimens data that will be used to define biomarkers of PN. Once these biomarkers are defined, they can be used in therapeutic studies, which is the ultimate goal
The PNRR creates a bio-bank of blood and DNA of well-characterized patients with various forms of peripheral neuropathy and lays the foundation for future clinical trials with these motivated patients.
The data collected in the PNRR will ultimately result in the improvement of the ability to diagnose, treat, prevent and eventually, cure peripheral neuropathy.