Selected recent issues of NeuroPerspective are available for purchase on a single-purchase basis.
The September/October 2019 issue of NeuroPerspective features our comprehensive annual review of the Alzheimer’s space, including a review of the current conceptual trends vis-a-vis pathophysiology, mechanisms, and therapeutic targets. 2019 has seen greatly expanded efforts aimed at harnessing neuroimmunological components in the service of avoiding toxic levels of inflammation, while promoting microglial clearance of aberrant protein aggregates. There has also been a willingness to fund novel models for AD and its treatment, including infection models. This is not to completely dismiss the most recent iterations of the ‘amyloid theory’, beta amyloid oligomers are clearly toxic and play some role in the Alzheimer’s process, including setting the stage for tau aggregates to inflict damage. The original amyloid hypothesis, featuring plaque as the active edge of pathology, is an anachronism, we are just beginning the process of vetting the role of tau and tau therapeutics in clinical AD.
Among the 200+ programs assessed are those from: AbbVie, Alector, AC Immune, Allergan, Alkahest/Grifols, Anavex, Asceneuron, Axon-Neuroscience, Biogen, Cognition Therapeutics, Cortexyme, Denali, EIP Pharma, Eisai, E-Scape, Genentech, JNJ, Klogene, Lilly, Lundbeck, Merck, Novartis, Oryzon, ProMIS, Roche, Rodin Therapeutics, Takeda, TauRx, Tetra Drug Discovery andVoyager. Cortexyme and Rodin Therapeutics are the foci of the two Company Review> sections; sidebars include coverage of the current state of the AD Biomarker art and an overview of the POC timelines for major AD programs.
The Sept/Oct issue also includes a full review of Frontotemporal Dementia (FTD), including an evaluation of the complex heterogeneity within this umbrella category, with marked divergences in genotype and phenotypic signs. FTD programs are evaluated, including those from AbbVie/Alector, Biogen, Aquinnah, and Wave Life Sciences/Takeda.
Commentary covers such diverse topics as Novartis Zolgensma faux pas;Marinus’ lackluster PPD results;AbbVie’s PSP failure, Vanda’s ‘perplexity’, and the impending battle between Jazz and Harmony in the narcolepsy space.
The July/August 2019 issue overviews developments in the neuro sector YTD, including coverage of paradigm shifts in the treatment of depression, SMA, and migraine. Capsule summaries for 80+ companies are included, plus commentary regarding trends in investment and partnership dynamics. Migraine is reviewed in full for the first time in four years, with an assessment of the CGRP-target reconfiguration of the migraine market, both via the injectibles and the coming oral options from Allergan and Biohaven. The July/August issue also provides an overview of E-Scape Bio.
The first therapeutic sector review covers Multiple Sclerosis, which to some degree represents the kind of therapeutic efficacy and choices that the rest of the neurotherapeutics area aspires to achieve, but remains problematic for some populations and in the risk-benefit profiles available for the disease modifiers. Biogen's commercial dominance is being threatened by the highly successful advent of Roche's Ocrevus and what will eventually turn into a parade of patent expirations. Progressive MS, both Primary and Secondary, has only begun to be addressed by Ocrevus and Mayzent, and with far less impact than can be brought to bear on Relapsing-Remitting MS. Even in RRMS, patients have generally had to confront a choice between efficacy and safety, where the most impactful therapeutics also come with the most dire adverse event risks (e.g. Tysabri and PML). Beyond disease-slowing, MS is the context where regenerative therapies are most likely to first make their mark in the neuro field, with remyelination high on the priority list. In terms of high profile programs, the development of new targets in neuroinflammation is very applicable to MS, with programs from Sanofi/Denali, Merck KGa, Annexon, and Disarm Therapeutics among the most interesting approaches. Remyelination/regeneration is the goal of programs from AbbVie, Biogen, and Roche/Inception 5, with ‘inhibiting the inhibitors’ and fostering oligodendrocyte differentiation standing out as the primary tactics.
The second therapeutic sector review covers Insomnia, an area which is dominated by GABAergic generics, but is also the context for the therapeutic elucidation of the orexin receptor system as a means of modulating wakefulness and sleep. There is an active debate as to how best utilize the orexin system, via dual receptor agonists, as was the case with Merck’s Belsomra (as well as Eisai/Purdue, Idorsia), or selective orexin-2 agonists, such as Minerva Neuroscience’s seltorexant. The FDA’s priorities have gone somewhat askew in the insomnia field, with a preoccupation with rare side effects and subtle decrements in ‘next-day driving’, which are less of a real-life problem than untreated insomnia and the heavy reliance upon OTC soporifics which have substantial next-day residual effects.
The May/June issue also includes discussion of recent developments for companies addressing depression (JNJ/Janssen, Allergan); substantial doubts regarding the viability of NGF mAbs in pain; and the obstacles the FDA has been presenting to pain companies, particularly in the ‘abuse-deterrent’ space.
The March/April 2019 issue of NeuroPerspective provides detailed reviews of two therapeutic areas, as well as coverage and commentary regarding significant developments in the CNS therapeutics space.
The first therapeutic sector review covers Schizophrenia, the most devastating of all the psychiatric disorders, one which comprises the awkward melding of multiple schizophreniform phenotypes 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. At its root, schizophrenia most likely arises from neurodevelopmental failure exacerbated by the degenerative impact of aberrant adolescent synaptic 'pruning,' perhaps reflecting aberrant neuroinflammatory/immune system activity. Network deficits account for the neural dyscontrol that sets the stage for hallucinations/delusions, and for the impoverishment of cognitive capabilities and motivation. While there is promising work on neuroinflammation currently ongoing, with a predominant focus on neurodegeneration (e.g. Alector, Annexon, Denali), the potential application of that work to schizophrenia lags far behind. Symptomatic treatments for schizophrenia are still the currency of the clinical practice and clinical development realms: Current therapeutics are almost solely aimed at the so-called positive symptoms of schizophrenia, there has been no real 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: Biogen,Intra-Cellular Therapies, Karuna Pharmaceuticals, Cerevel, Allergan, Boehringer Ingelheim, Sage Therapeutics, Lundbeck, Takeda, Acadia, Promentis, Newron, Syndesi, SyneuRx, and Sunovion.
The second therapeutic sector review covers Stroke, an area which became anathema to the pharma industry after a series of clinical failures 15-20 years ago. With almost 800,000 stroke cases annually in the US alone, this neglect (which had left stroke R&D primarily the province of endovascular device companies) has been untenable in the long run. Biogen is the first of the major pharma companies to make a return to stroke, via partnerships with Remedy and TMS. There is work on extending the window for thrombolytic interventions (ActiCor, Biogen), solving the seemingly intractable puzzle of neuroprotection (NoNO, AdMIRx, Avilex, ZZ Biotech), and a growing emphasis on repair/regeneration, particularly by the several cell therapy companies engaged in that work (Athersys, SanBio, NeuralStem, ReNeuron). Programs from BioAxone and Idorsia address hemorrhagic stroke. Other companies and academic centers whose programs are discussed in this review include: UCLA, ArunA, NeurOp).
The March/April issue also includes discussion of recent clinical findings from companies addressing depression (JNJ/Janssen, Sage Therapeutics,Axsome, Blackthorn Therapeutics); high-innovation partnerships for Voyager with AbbVie and with Neurocrine, Biogen with C4T and Skyhawk, and possible salvation for the PTSD program from Bionomics. The Company Spotlight Review covers SyneuRx, which is in PhII/III trials using sodium benzoate/NaBen for schizophrenia and dementia.
The January/February issue of NeuroPerspective has been released. It provides a comprehensive review of 2018, and a full appraisal of what to anticipate in 2019. 130 companies have capsule summaries of current activities and coming events, including AbbVie, Acorda, Adamas, Alkahest, Alkermes, Allergan, Biogen, Biohaven, Blackthorn, Denali, JNJ, Lilly, Lundbeck, Lysosomal Therapeutics, Marinus, Minerva, Neurocrine Biosciences, Novartis, Ovid, Perception, Pfizer, Roche, SAGE, Sunovion, Teva, Voyager Therapeutics, Wave Life Sciences, Xenon, Yumanity, Zogenix, and one hundred more.
Highlights and Lowlights from 2018 are assessed, with particular consideration of 2018's record inflow of financial resources from both investors and pharma partners; Roche/Ionis's preliminary data in Huntington's; the anticipated advent of SAGE's Zulresso, as well as the status of potential competition from Marinus in Post-Partum Depression; Biogen's first foray into Psychiatry; the FDA's support for trials of MDMA and psilocybin in a number of psychiatric disorders; the ambiguous impact of JNJ's esketamine as a treatment adjunct; and the disappointment of BioAxone's Cethrin in Spinal Cord Injury. For the first time in a couple years, NP has named recipients of our awards for Best and Worst CEO.
This issue also includes a guest article from Joel Sanders PhD (Cello Health) reviewing the expanding range of gene therapy programs in neurodegeneration, including Novartis/AveXis, Biogen/Ionis, PTC/Agilism AbbVie/Voyager, Takeda/WAVE, and many more. The Jan/Feb NP also provides a succinct review assessing the rise of digital technologies in clinical trials and treatment, via companies like MindStrong, AiCure, TrialSpark, Science 37, Pear Therapeutics, Click Therapeutics. HeadSpace, and DThera.
The Company Spotlight covers Syndesi Therapeutics, developing procognitive compounds spun out by UCB Pharma.
The November/December issue of NeuroPerspective features a comprehensive review of the Pain space, divided into two major sub-sections, Nociceptive (including Inflammatory) Pain and Neuropathic Pain. Even as attention has necessarily been focused upon the Opioid Epidemic that had its roots in an overreliance upon prescription opioid analgesics, the Pain field has yet to develop non-opioid alternatives that provide sufficient analgesia for severe pain. Some companies have focused upon developing modestly-less-abuse-prone opioid reformulations, these have failed to impress regulators or prescribers. Trevena's 'biased agonists' represented an unacceptable trade-off of efficacy for safety, while NGF antibodies have had a torturous path through clinical and regulatory challenges, and are burdened by their own safety risks. Extending the range of short-acting anesthetics in order to circumvent the need for post-operative opioids is a strategy that has shown some promise. Neuropathic pain is in some ways even more ephemeral and frustrating, there has yet to be a 'gold standard' for neuropathic pain, which comes in several major sub-varieties, and for which current treatments tend to offer only partial relief to a minority of patients.
Among the 60+ programs are assessed are those from: Centrexion, Lilly/AstraZeneca, Teva/Regeneron, Trevena, Vertex, Cara Therapeutics, Wex Pharmaceuticals, Mesoblast, Adynnx, Recro, Novartis/Spinifex, Xenon, Astraea, Coda Therapeutics, Aptinyx, and Amgen. The Boehringer Ingelheim licensing agenda is excerpted from NeuroLicensing 2018-19. Sidebars include coverage of JNJ esketamine program in depression; competition rapidly pursuing Biogen's Spinraza, the ambiguity of Eisai/Biogen's BAN2401 data in Alzheimer's, and the ADCOM rebuff of Alkermes' highly flawed NDA submission for ALKS 5461. 53 pages.