The September/October issue of NeuroPerspective features our annual, epic, and comprehensive review of the Alzheimer’s space, including a review of the current thinking around pathophysiology and therapeutic targets. The subtitle for the review is ‘Reset, Reboot,Recalibrate’, because the traditional modus operandi for the Industry in its approach to AD has produced a series of disspiriting failures. An updated assessment on the roles of amyloid, tau, neuroinflammation, and other targets is included. Among the 150+ programs are assessed are those from: AbbVie, AB Science, AC Immune, AgeneBio, Allergan, Alkahest, Anavex, Asceneuron, AstraZeneca, Axon-Neuroscience, Axovant, Biogen, Cognition Therapeutics, Cortexyme, Denali, Eisai, E-Scape, Genentech, Intra-Cellular, JNJ, Karuna, Lilly, Lundbeck, Merck, Novartis, Oryzon, Pfizer, Prana, Probiodrug, Proclara, ProMIS, Roce, Takeda, TauRx, Tetra Drug Discovery, United Neuroscience, and Voyager. Alkahest is the focus of the Company Review, sidebars include coverage of the current state of the AD Biomarker art and a consideration of the POC timelines for major AD programs.
The Sept/Oct issue also includes a full review of ADHD, including the search for nonstimulant options that might approach the efficacy of the psychostimulants. Programs from Aevi, Alcobra, NLS Pharma, Otsuka/Neurovance, Sunovion, and Supernus are among those assessed in the review.
The March/April issue of NeuroPerspective for 2017 offers detailed reviews of HD and Elilepsy.
Huntington’s offers more mechanistic clarity than its neurodegenerative peers, though the route from genotype to phenotype remains to-be-defined, and the mHtt target grows more complex and multi-faceted the more that it comes into focus. Operating against the genetic anomaly would require the selective sparing of necessary wild-type Htt, and the delivery of large molecules through the BBB and deep into the brain. Which means that upstream clarity does not easily translate into downstream impact. The size of the Huntington’s-yet-to-emerge patient universe is in the 150-200,000 range in the US, making this far more than a minor market for any company that can develop a disease-slowing treatment. Such a drug would be administered early, and perhaps chronically. The advent of a disease-modifier would also invert the risk-benefit calculations involved in genetic testing: The diagnosis would finally be more than an incontrovertible harbinger of personal doom. Some of the companies whose programs are discussed in the review include: Annexon Biosciences, Proclara, Roche/Ionis, Wave Life Sciences, Spark Therapeutics, Teva, UniQure, Voyager, Prana, Evotec/CHDI, and Vaccinex.
The second therapeutic sector review is on Epilepsy: The current armamentarium of anti-epileptic drugs offer numerous variations on a few main themes; none of which have proven superior across the board; and which singly or in combination, provide adequate control for just 70-80% of epilepsy patients. For a patient formerly refractory to drug treatment, achieving seizure control, via monotherapy or adjuncts, can be a life-saving event, literally and figuratively. Improving tolerability, and reducing teratogenicity and/or weight gain, would also improve treatment compliance and outcome.The most dramatic advances on tap for the next few years involve relatively small, but severely-impacted subpopulations. Severe Refractory Status Epilepticus appears solvable for many via SAGE-547, while significant (though far from ideal) inroads are now being made with Dravet Syndrome and Lennox-Gestaut, generally refractory to intervention, by companies like GW Pharma and Zogenix. Big Pharma has largely withdrawn from the development of epilepsy drugs, as exemplified by Lilly's outlicensing LY3130418 to Cerecor, and JNJ/Janssen not pursuing its own promising TARP/AMPA inhibitors. In contrast, UCB Pharma has made epilepsy the centerpiece of its research and commercial strategy, although recent partnerships have been turned to neurodegeneration as they gradually broaden their focus. Of the other companies tracked in NeuroLicensing 2016-17, only Dainippon/Sunovion and Otsuka cited Epilepsy as an area where they have licensing interests. This means that drug development for Epilepsy has become the province of small and mid-sized specialty companies, and funding has not been easily found, in spite of the unmet needs that continue to be high-profile in this population. The companies whose programs are discussed in this review include: SAGE Therapeutics, GW Pharma, UCB Pharma, Marinus Pharmaceuticals, Zogenix, Epalex, Cerecor, Tansna Therapeutics, Zynerba, Catalyst Pharma, SK Biopharma, Neurona Therapeutics, and Adamas Pharmaceuticals.
The March/April issue also includes discussion of recent clinical findings from Trevena, Merck, Acorda, and Celgene, as well as commentary on the pricing debacle at Marathon Pharmaceuticals and questions regarding Alcobra’s revised strategy. Company Spotlight Reviews are included for Wave Life Sciences and Trevena.
The first therapeutic sector review covers Schizophrenia, the most devastating of all the psychiatric disorders, one which reflects the awkward melding of multiple schizophreniform disorders with very divergent symptom patterns. Affecting about 1% of the population, schizophrenia's genetic vulnerabilities are complex and contribute to schizophrenia's etiological confluence of genetic flaws, prenatal/perinatal environmental factors, and later anomalies in the formation and 'editing' of synaptic networks. While still speculative, it does appear that at its root, schizophrenia arises from neurodevelopmental failure exacerbated by the degenerative impact of aberrant adolescent synaptic 'pruning.' Network deficits account for the neural dyscontrol that sets the stage for hallucinations/delusions, and for the impoverishment of cognitive capabilities and motivation. Current therapeutics are solely aimed at the so-called positive symptoms of schizophrenia, to this point no one has had success developing treatments for the cognitive and negative symptoms that take such a functional toll, even when the more florid symptoms of schizophrenia are relatively controlled. Some of the companies whose programs are discussed in the review include: Annexon Biosciences, Allergan, SAGE Therapeutics, Takeda, Merck/Bionomica, Acadia, Promentis, Newron, Intra-Cellular Therapies, Karuna Pharmaceuticals, and Sunovion. With Tardive Dyskinesia one of the horrific legacies of an earlier era of antipsychotic treatment, the issue also assesses the two new entrants for the treatment of TD, from Neurocrine Biosciences and Teva.
The second therapeutic sector review covers Insomnia, which has seen the development of a novel mechanistic approach (orexin antagonism), despite the plethora of relatively effective but imperfect GABAergic sedative-hypnotics already available. Those drugs have a number of shortcomings, but create a genericized environment that constitutes a significant commercial challenge. This has been tackled by Merck's suvorexant/Belsomra, handicapped by FDA-imposed dosing recommendations that recommended a subclinical dose, ensuring that many prescribers and patients would be initially dissatisfied. Merck has not broken out its sales figures, which is a sure sign that they lag expectations. The other companies whose programs are discussed in this review include: Eisai/Purdue Pharma, Minerva Neurosciences/JNJ, Ferrer/Ergomed, Intec Pharma, and the Actelion spin-out company.
The May/June issue also includes discussion of recent clinical findings from AveXis, Neuren, Catalyst, and Allergan, as well as commentary on the dismantling of BMS' CNS portfolio and the emergence of BioHaven; and the activist investor putsch at Depomed. Company Spotlight Reviews are included for BioHaven Pharmaceuticals and Karuna Pharmaceuticals. 54 pages.