Prize4Life recently attended the 9th Annual Neurotech Investing & Partnering Conference, Advances in Drugs, Devices & Diagnostics for the Brain and Nervous System hosted by the Neurotechnology Industry Organization (NIO) and NeuroInsights held April 23-24, 2014 in Boston, MA. For those of you who unfamiliar with NIO, it is a non-profit trade association for neuroscience-focused companies founded in 2006 to accelerate the development of treatments and cures for brain and nervous system illnesses. The Conference provides a stimulating forum for discussions between pharma, biotech and investors on recent trends in development of diagnostics, therapeutics, and medical devices for neurological diseases. Prize4Life’s Executive Director, Dr. Sara Shnider, attended the meeting and reported on the session on “Parkinson’s and Other Movement Disorders”. Although the session focused on Parkinson’s disease, the challenges of therapy development raised in the session, such as how to improve drug delivery to the central nervous system and evaluating clinical trial results with subjective outcome measures, are common to ALS and other neurodegenerative diseases.
The session of Parkinson’s and Other Movement Disorders highlighted key challenges with drug delivery into the CNS. The moderator of the session, Manuel Lopez Figueroa, Vice President of Bay City Capital, provided context to discussion of Parkinson’s disease (PD) with the staggering statistics that 1.5 million Americans live with PD, making it the 14th leading cause of death in the United States. He also cited the high costs of the disease, estimated to be approximately $14 billion dollars per year, including direct and indirect costs. The market for PD drugs is greater than $2.2 billion dollars per year, however none of the available medications are able to reverse or attenuate progression of the disease. Although the past year did not bring new therapies into the clinic, it has been a productive year for developing new delivery systems for PD, which will be the focus of the session.
Glenn Batchelder, CEO and co-founder of Civitas Therapeutics opened the session. Chelsea, MA-based Civitas Therapeutics is developing breakthrough therapies based on their proprietary technology that enables respiratory delivery of a large, precise dose of L-Dopa with a simple, convenient, breath-activated device. L-Dopa remains the gold standard for treatment of PD, and is prescribed to over 75% of patients with PD. However, over 50% of patients taking this medication suffer from phases called “OFF periods”, when symptoms become overwhelming and the medications are ineffective. The reason for these OFF periods is the sharp dose response to this drug, where small changes in plasma levels lead to large changes in motor function, and a small drop in plasma concentration can be debilitating. The inherent variability of the oral route results in unpredictable efficacy, which Civitas has overcome with their pulmonary delivery approach.
CVT-301 is a pulmonary delivery system for L-Dopa, which delivers drug directly to the plasma thereby overcoming the large concentration shifts observed after oral administration. CVT-301 will empower patients to take control during the OFF periods, when oral L-dopa fails. The company has completed Phase I and IIa studies, achieving clinical proof-of-concept and dose selection, and they have already received supportive FDA feedback on their development plan. They have also confirmed insurance coverage of this therapy at an attractive price.
Mark Pykett, CEO of Navidea Biosciences followed with new diagnostic tools for PD. The focus of the company is precision diagnostics for detecting the presence and status of disease, and they are particularly interested in repurposed drugs in order to accelerate the approval for use in humans. The company received FDA approval in early 2013 for Lymphoseek, a diagnostic for use in lymphatic mapping procedures to help localize lymph nodes draining a primary tumor in patients with breast cancer or melanoma. Currently under development are NAV4694, being evaluated in Phase IIB and III for diagnosis of Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI), and NAV5001 for diagnosis of PD, and Dementia with Lewy Bodies.
NAV5001 is a small molecule radiopharmaceutical imaging agent labeled with iodine 123 that bind the dopamine transporter (DAT) and specifically labels dopaminergic neurons in the striatum and substantia nigra. Due to the increased thermal and radiologically stability of NAV5001 as compared to the commonly used imaging agent, ([123)I]ioflupane, and its greater selectively for DAT, the imaging time required using NAV5001 is only a fraction of the time required with ioflupane (45 min. as compared to 4-6 hours). Navidea is currently in Phase III clinical studies for PD, and a Phase IIb for Dementia with Lewy Bodies. Since this drug has already been in >600 patients in clinical studies, it already has a demonstrated safety profile. Dr. Pykett mentioned the challenging regulatory environment for diagnostics caused by the decision of the Centers for Medicare & Medicaid Services (CMS) in July 2013 not to allow wider reimbursement for amyloid positron emission tomography (PET) for the evaluation of dementia and neurodegenerative diseases, including Alzheimer’s disease. It is unclear what the reimbursement landscape will be for new diagnostics of neurodegenerative diseases, but it is clear that it will be important to demonstrate that the diagnostic can improve treatment through early diagnosis and risk stratification of patients.
Next, Kevin Gorman, the CEO of Neurocrine Biosciences discussed their groundbreaking new therapeutic for treating patients with tardive dyskinesia of (TD). This disorder involves involuntary, repetitive movements primarily of the facial muscles, which often develops following prolonged periods of taking antipsychotic drugs. Neurocrine has developed NBI-98854, which is currently in Phase II trials for the treatment of TD. Dr. Gorman discussed the challenges in the regulatory process for TD, being the first company to begin a registration procedure for this disease. One of the primary challenges was the requirement by the FDA that the accepted evaluation measure for TD, the Abnormal Involuntary Movement Scale (AIMS). However, the rating scale has a limited scoring range from 0-4 for each body regions, and the patient scoring by physicians at different sites was inconsistent between physicians and across clinical trial sites, confounding the results. By post-hoc analysis of the video-records AIMS tests from the failed Phase IIb trial, they found a large, statistically significant benefit to their therapy, which had been overlooked due to variability in the scoring system across sites. The lessons learned from their Phase IIb trials were that for this type of subjective measure, the AIMS testing needs to be performed by a second physician who was not involved in administering the drug, and more importantly, scoring requires a central review by blinded observers applying consistent criteria across all participating patients. Dr. Gorman underscored the value of the fast-track designation, which enabled the company to have frequent conversations with the FDA to ensure a clear path toward regulatory approval of their drug.
The final presenter was Randall Moreadith, CEO of Serina Therapeutics. Serina Therapeutics is a pharmaceutical company that has developed a safe, water-soluble polymer to which they can attach a variety of small molecules, proteins, peptides and DNA. The attachment of these molecules to their polymer typically alters the pharmacokinetic properties of the original compound, thereby improving the safety and efficacy profile of the original drug. One example is their clinical candidate for treating PD by providing continuous dopaminergic stimulation. They have developed a sustained release L-Dopa compound called SER214, which is very effective at reducing OFF times that are typical of L-Dopa therapy. In the MPTP primate model, a single subcutaneous injection of SER214 promotes prompt and sustained improvement in motor function, and the monkey do not develop dyskinesia. The company has already performed most of the IND-enabling studies, and plans to apply for Breakthrough Designation.
The follow up discussion focused on the partnering landscape for PD, which is usually in the shadows of Alzheimer’s disease in terms of financial investments. Partnership opportunities appear to be great for companies developing new drugs, as opposed to improved delivery systems for old drugs. With respect to the diagnostics for PD, Navidea is optimistic that the key is validation, and that a well validated imaging biomarker will lead to productive partnership opportunities. The panel concluded with a discussion of the impact of Medicare reimbursement and the payers, given the challenging environment for diagnostics and symptomatic treatments. The panelist reiterated the undeniable unmet need in PD, and their expectation for increasingly strict pricing requirements for novel drugs. – Sara Shnider