Journal of the Peripheral Nervous System 19(Supplement):S28–S29 (2014)

Conclusions

Designing innovative therapies for neuropathic pain:preclinical and early clinical development challenges

A Höke1, DM Simpson2, and R Freeman3

1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Department of Neurology,Mount Sinai School of Medicine, New York, NY, USA; and 3Department of Neurology, Harvard Medical School, Beth Israel

Deaconess Medical Center, Boston, MA, USA

The second scientific meeting of the Foundationfor Peripheral Neuropathy was successful in bringingtogether basic and clinical scientists from academia,National Institutes of Health (NIH), and industry toidentify the challenges in Preclinical and Early ClinicalDrug Development for Neuropathic Pain. The meetingfocused on preclinical drug development approachesand challenges in phase II trials for neuropathic pain.In the preclinical stage, advantages and disadvantagesof phenotypic and candidate molecular target basedscreens were discussed along with the new role aca-demic drug discovery centers are playing in early drugdiscovery. These are outlined in three articles by Drs.Slusher, Enna, and Inglese. After outlining some of thepotential new drugs for neuropathic pain, four industryexperts led a roundtable discussion on industry’s per-spective on developing drugs for neuropathic pain. Thesecond half of the meeting focused on challenges inphase II trials of neuropathic pain. Several issues wereidentified. These include:

• Discrepancy in defining peripheral neuropathy aseither a disease or syndrome.

• Inclusion/exclusion criteria in studies have not beenstandardized. Among the factors related to thisissue are confounding disorders, concomitant med-ication usage, and identifying representative patientpopulations.

• Outcome measures with respect to pain intensityhave not been clearly defined and are difficult toquantify.

• The placebo effect plays a significant role in studiesand impacts data analysis (variation in response:20–70%).

• Resource limitations due to funding and the chang-ing landscape of the research field.

• Data sharing: confidentiality vs. open access.

Discussions at the meeting led to the recogni-tion that at the preclinical stage there will be room

for both phenotypic and mechanism-based screen-ing approaches, with a greater involvement of aca-demic drug discovery centers than we have experi-enced in the past. Partnerships between academia andindustry will align the academic scientists’ expertisein disease and animal models with the drug discov-ery expertise of academic centers and industry andwill likely result in faster identification of candidatedrugs.

On the clinical end, there is an urgent needto develop resources for biomarker discovery andinfrastructure for academic clinical trials. The Periph-eral Neuropathy Patient Registry (PNRR), funded bythe Foundation for Peripheral Neuropathy is such aresource.

The rationale and aims of the PNRR:

• Stored biological samples collected throughout thecourse of PNRR in a central repository that will beaccessible to any scientist with promising biomarkerleads for the purposes of verifying initial results andassessing correlations to clinical outcomes and otherbiomarkers.

• Identify phenotypic clinical features of patients withneuropathic pain.

• Improve and/or assist with clinical trial recruitmentprocess.

• Develop a comprehensive and uniformly acquiredclinical dataset with correlated biological samplesthat can be used in biomarker verification studies.

• Establish standardized protocols for acquisition,transfer and analysis of clinical data, and biolog-ical samples that can be used by the researchcommunity.

• Create standardized data protocols to ensure thattests and assessments conducted at multiple sitesand across multiple cohorts can be pooled andshared in the clinical community.

• Establish a comprehensive set of clinical biospeci-mens data that will be used to define biomarkers of

© 2014 Peripheral Nerve Society S28

Höke et al. Journal of the Peripheral Nervous System 19(Supplement):S28–S29 (2014)

peripheral neuropathy (PN). Once these biomarkersare defined, they can be used in therapeutic studies,which is the ultimate goal.

The PNRR creates a bio-bank of blood and DNAof well-characterized patients with various forms of

peripheral neuropathy and lays the foundation forfuture clinical trials with these motivated patients. Thedata collected in the PNRR will ultimately result in theimprovement of the ability to diagnose, treat, prevent,and eventually cure peripheral neuropathy.

S29