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Saturday, April 13, 2019

As spin-out, Alcon joins a successful crowd

  • Novartis spin-off Alcon began life as an independent company in the green Tuesday, a start that aligns with the historically positive market reception for companies spun out from their parents in both pharma and the broader business world.
  • Since 2010, major pharma spin-offs have outperformed the S&P 500 by a median return of 5% in the first month of trading, according to an analysis by RBC Capital Markets published Wednesday. That success holds true for other industries as well, the investment bank found, citing data from the Bloomberg U.S. Spin-Off Index showing spin-offs outperformed the market at an increasing rate over the past decade.
  • That trend, coupled with Novartis’ successful move to shed Alcon, could potentially serve as a blueprint for Allergan, a pharma facing growing investor discontent, RBC analyst Randall Stanicky wrote. After four years of consistent share price declines, shareholder frustration could be in the spotlight at Allergan’s May 1 meeting, which will feature a non-binding vote to separate the CEO and chairman roles.

Novartis’ spin-off of Alcon was the result of a 2017 strategic review. The newly independent company, which employs more than 20,000 staff, will focus on a portfolio of eye care products that earned sales of $7.1 billion last year.
Spin-offs are largely aimed at generating greater stock returns, and RBC’s analysis found such moves have been largely successfully in achieving that goal — judging by their short-term stock market performance, at least.
PARENTSPIN-OFFDATE COMPLETEDSPIN-OFF 1-MONTH PERFORMANCESPIN-OFF 12-MONTH PERFORMANCE
NovartisAlconApril 2019N/AN/A
Eli LillyElancoSept. 2018-12%-9%
PfizerConsumer healthIn processN/AN/A
BiogenBioverativFeb. 201718%133%
BaxterBaxaltaJuly 20154%46%
Reckitt BenckiserIndiviorDec. 20146%20%
TheravanceTheravance BiopharmaJune 201474%-29%
PfizerZoetisFeb. 201312%-2%
AbbottAbbVieJan. 20136%48%
Average15%30%
Median6%20%
SOURCE: RBC Capital Markets
In the case of Allergan, shareholders may be taking a closer look at Novartis’ decision.
“The solid historical performance of spin-offs suggests that it could be a compelling alternative to a sale or divestiture should Allergan pursue a break-up,” Stanicky wrote.
While non-binding, the May 1 vote on splitting the CEO and chairman roles could hold broader implications for Allergan’s future direction, according to the analyst.
Stanicky advocates for a business break-up and expects the board to feel more pressure if the vote garners majority support. He isn’t alone either, as Bernstein analyst Ronny Gal recently called for a split of Allergan’s aesthetics and therapeutics businesses.
“We believe management should address such split plans explicitly in the upcoming quarterly call,” Gal wrote, referencing Allergan’s first quarter earnings call set for May 7.
The Dublin-based pharma has been here before. As part of a strategic review a year ago, CEO Brent Saunders said  “everything was on the table,” including a split.
That process led Allergan to announce plans last May to sell its women’s health and infectious disease businesses. But neither have been sold yet, and Saunders said earlier this year the company would no longer attempt to find a buyer for its women’s health unit.
The stock market hasn’t been kind to Allergan. Share prices have declined more than 50% since 2016, and a string of R&D failures have lowered long-term growth expectations.
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Why Alder thinks its late-comer migraine drug can succeed

A clutch of new preventive therapies jolted the migraine market in 2018, with three similar drugs from Amgen, Teva and Eli Lilly launching within months of each other.
While those large drugmakers elbow for commercial advantage, a small biotech in the Pacific Northwest has been planning a fourth-to-market launch that could add a new competitive wrinkle.
The odds are stacked against Alder BioPharmaceuticals, a company of about 200 based in Bothell, Washington. This February, Alder filed an application for U.S. approval of its drug eptinezumab, which blocks a protein called CGRP that’s also the target of the therapies from its three would-be pharma rivals.
Alder is planning for an early 2020 launch, a timeline that even if all went right would put eptinezumab more than a year behind. Its competitors are also industry-leading giants, with employees by the tens of thousands.
But Alder doesn’t think it would need a large salesforce to compete, according to Robert Azelby​, who joined Alder last June as its CEO. He predicted a specialty launch, tailored to a specific group of prescribers, would yield success if eptinezumab were to win approval.
“I would anticipate that Alder goes it alone in the U.S.,” Azelby​ said in an interview with BioPharma Dive, adding Alder would consider an ex-U.S. commercial partnership.
Instead, Azelby​ expects a salesforce of 75 to 100 people that will focus on a small group of specialist doctors who do most of the prescribing for these migraine therapies. Per market research done by the company, roughly 3,000 doctors are writing 80% of the prescriptions for CGRP inhibitors, and 800 of those doctors account for half of all anti-CGRP prescriptions.
“We don’t need armies of people going out and calling primary care because these patients are being seen by this concentrated group of physicians,” said Azelby​, previously an executive for Amgen and Juno Therapeutics.
That Alder thinks it can make a mark with eptinezumab speaks to the blockbuster sales expectations for the preventive migraine market overall. Sales of the three approved drugs have been modest to date, but prescription numbers suggest continued uptake of the drug class.
For better or worse, eptinezumab carries a clinical difference from the anti-CGRPs developed by Amgen, Lilly and Teva. While those three are administered subcutaneously once a month, Alder’s drug is given through a quarterly IV infusion. Teva’s drug, Ajovy (fremanezumab), also has quarterly subcutaneous dosing.
“There’s no advantage of being an IV because patients are going to choose what they can get,” Andrew Hershey, a headache medicine specialist at Cincinnati Children’s Hospital  said in an interview with BioPharma Dive. The migraine expert added CGRP choice has really been determined by the insurance companies, and believes the IV requirement could make it a less attractive option. Hershey has previously disclosed consulting ties to Amgen and Lilly.
Azelby​, on the other hand, spins the IV requirement as a perk, requiring less frequent treatment than the other options and associated with a rapid reduction in migraine risk in the first 24 hours after infusion.
Paul Matteis, an analyst with Stifel, shares Azelby​’s view, arguing in a recent note to investors that payers are likely to bucket all three subcutaneous drugs together, potentially helping boost coverage of eptinezumab. Still, Matteis believes Alder’s drug will command only a “meaningful minority share.”
In addition to whether doctors will be convinced of eptinezumab’s benefit, another question hangs over Alder.
As a regulatory decision and potential launch nears, it relates to M&A, something perhaps made more relevant given Azelby​’s background.
The exec was last at Juno, which was bought out by Celgene in a multi-billion dollar deal in 2018. He also sits on the board of Clovis Oncology, whose own chief executive has not been shy about his desire to be bought.
Some Wall Street analysts have wondered of a similar ending to Alder’s story. Cowen & Co.’s Ken Cacciatore, for one, noted a sale would remove from Alder the burden of building a commercial presence.
“We are hopeful that Alder will be sold and therefore not have to add another salesforce and promotional effort into this category,” Cacciatore wrote in February in a note to investors.
When asked directly on the company’s M&A attitude, Azelby​ demurred, saying his Juno experience taught him to not think much about the M&A side.
“That’s going to be a determinant of a third party that would like to acquire us and their engagement with the board,” he said, adding his focus is on executing the launch well. “If we do those things, it’s going to bring shareholder value as well as benefit to patients in either scenario, whether we stay it alone as an independent or if we are acquired.”
The company has moved forward with preparations to launch by itself, naming a chief commercial officer earlier this week in Nadia Dac, previously AbbVie’s vice president of global specialty commercial development.
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Barriers to Telehealth Adoption Remain

Fitting telehealth into the daily flow of a medical practice is the biggest perceived barrier to telehealth adoption, according to a survey conducted by the American College of Physicians (ACP).
“One of the biggest challenges … is that members struggle with how to integrate telehealth into their practice workflows,” said Tabassum Salam, MD, the ACP’s vice president for medical education, speaking at the group’s annual meeting here.
“They want to figure out which patients are good candidates for telehealth, and they have to figure out how to change their procedures and incorporate new types of visits into these practice workflows.”
The ACP surveyed a random sample of 1,449 members ages 65 and younger in October 2018 and in January 2019; completed responses came from 233 members; 72% were general internists and 28% were subspecialists. Types of telehealth included in the survey included video visits, e-consults, remote patient monitoring, remote care management and coaching, and data from wearables.
The rate of adoption and usage varied widely depending on the type of technology involved, although 51% of respondents said they used at least one of the five categories of telehealth technologies. E-consult technology, in which physicians use either real-time or “store-and-forward” virtual communication tools to consult about a patient, was the most widely used technology, at 33% of respondents. Of those who used e-consults, 63% said they used them every week. Remote care management and video visits were less widely used, by 24% and 18% of respondents, respectively.
Among survey respondents, perceived barriers to adoption of telehealth included difficulties integrating it into the practice workflow (mentioned by 42% of respondents), no patient access to the technology (36%), concern about potential medical errors (29%), and security and privacy of patient information (23%).
image
(l-r) Ana Maria Lopez, MD, MPH, president of the American College of Physicians, and Tabassum Salam, MD, vice president for medical education, the American College of Physicians (Photo by Joyce Frieden)
“We do recommend physicians use their professional judgment over whether telehealth services are right for each patient and in each situation,” said Andrew Dunn, MD, chair of the ACP board of regents. However, he added, telemedicine has been proven highly effective in certain cases.
For example, the Indian Health Service ran a pilot telehealth program in Alaska which decreased the percentage of patients who had to wait at least 5 months for a new patient visit from 47% to 8%, “so it was a really dramatic improvement in access.” Another program run by the Department of Veterans Affairs showed a 20% reduction in readmissions with the use of telehealth services to improve home care for patients with multiple chronic diseases. “So it is very successful when used strategically,” said Dunn.
Barriers to telehealth still remain, including state licensure, he said. “Right now if you want to provide telehealth care across the state line, you probably need to be credentialed in both states and both hospitals … That’s a major barrier to what could be a big improvement in care.”
Another barrier is lack of good reimbursement models for telehealth “and the need for adequate technology on both sides: the transmitting side and the side of the receiving hospitals,” said Dunn. “We also want to make sure it doesn’t increase [disparities] in care between the haves and have-nots in the country; if you don’t have access to broadband technology, then you’ll be excluded from these benefits, and that’s a major concern to the college.”
There is some good news on the reimbursement front, he added: “As of January 1st, Medicare has established new payment codes for services provided using … virtual check-ins, e-consults, and remote evaluation of patient images. We’re very supportive of that.”
Telehealth technology is also getting better and cheaper, said ACP president Ana Maria López, MD, MPH. “Twenty years ago, the technology to give face-to-face video activity was about $100,000,” she said. “Currently, many systems are part of the electronic health record.” In addition, “With significant interest in how to implement telemedicine better, there are regional centers across the country available for people to go and say, ‘I want to do this; how do I do this?'”
Other findings from the survey included:
  • Among those with video visit technology, only 19% used it every week
  • Of those with remote care management technology, 50% used it every week
  • Among the technologies that respondents hadn’t implemented yet, 17% were considering implementing video visits next year, followed by remote patient monitoring and remote care management (both at 11%), physician e-consults (10%), and use of wearable data (9%)
The ACP is planning to develop some telehealth resources specific to internal medicine, Salam said. “Our initial focus will be on video visits, and then we plan to expand to other telehealth apps.” The resources will include guidance on appropriate use cases, workflow changes, the current state of reimbursement and regulatory issues, and a guide for practical selection of equipment and vendors. The material will be offered in multiple modalities, including online educational modules, web-based toolkits, and webinars, she said.
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The Bristol-Celgene merger is approved. Here are 8 challenges ahead

After months of horse-trading, hand-wringing, and heated debate, the $74 billion merger of Bristol-Myers Squibb and Celgene was finally approved by shareholders on Friday. “We’re very excited about the new company,” Giovanni Caforio, Bristol’s chairman and CEO, said at the meeting.
Now what?
Like Dustin Hoffman and Katharine Ross in the last scene of “The Graduate,” the two biopharma newlyweds got what they wanted, and now they’ll have to get used to one another’s idiosyncrasies. That means navigating a patent cliff, dealing with rough market dynamics, and trying to keep key employees from updating their résumés.
Here’s a look at the biggest issues facing Bristol-Myers and Celgene after their long-awaited union.

Revlimid and the patent cliff from hell

Congratulations, Bristol, you now own one of the largest drug-patent cliffs in the history of the pharma industry — $20 billion in Celgene product revenue (based on 2021 estimates) will disappear over the next nine years as generic competitors enter the market and gobble up market share.
Sixty percent of that liability falls on Revlimid, Celgene’s blockbuster multiple myeloma treatment. The first generic version of Revlimid is expected to enter the market in March 2022, but only on a restricted volume basis as dictated in a settlement agreement with the generic drug maker Natco Pharma. How fast Revlimid sales erode beyond 2022 remains undetermined because the legal wrangling continues between Celgene and generic drug makers. That fight is now Bristol’s.

Celgene’s pipeline must not stumble

Bristol acquired Celgene with full knowledge of the patent cliff, of course. Management’s working plan is to replace a good chunk of that lost revenue with newer drugs from Celgene’s pipeline.
Three of those Celgene drugs — fedratinib, ozanimod, and luspatercept — have been submitted to the Food and Drug Administration. If all goes right, fedratinib will be approved to treat myelofibrosis in September, with ozanimod (for multiple sclerosis) and luspatercept (for myelodysplastic syndrome and beta thalassemia) following in early 2020. Two CAR-T cancer therapies called bb2121 and liso-cel remain in late-stage clinical trials but are also crucial to the success of the Bristol-Celgene marriage. The margin of error for failures or delays is infinitesimally small.

Bristol’s cash cow is losing ground

Once upon a time, Bristol was at the vanguard of cancer immunotherapy. Back in 2016, the company’s Opdivo led the multibillion-dollar market and looked poised to maintain its lead. Then came a string of clinical trials that made Merck’s similar Keytruda look like the best product in the class, stealing market share from Opdivo and sliding Bristol’s therapy into second place.
That puts Bristol, which got about 30% of its revenue from Opdivo last year, in a tough spot. Opdivo is likely to face biosimilar competition in the next seven to nine years, and its diminishing stature in immuno-oncology underlines how much Bristol — like Celgene — needs next-generation cancer therapies to come through.

Keep the headhunters at bay

Mergers are not just about products and profits. People matter very much, too. Combining two large companies is never easy, but Bristol must be especially careful not to let talented scientists and businesspeople walk out the door because of intracompany rivalries or turf battles. Lifesaving medicines don’t just develop on their own. Want an early read on the success (or failure) of the Bristol-Celgene marriage? Check LinkedIn before the income statement.

Celgene’s many friends might have questions

Celgene has long been known as a ready and willing partner in biotech, and the company spent years stitching together a tapestry of deals that essentially gave it a call option on every new idea for treating cancer. Now, however, Celgene’s scores of partners might be wondering whether the combined company still values their relationships.
Some, like Bluebird Bio and Acceleron, have little to worry about, as their collaborations were name-checked by Bristol as keys to Celgene’s value. But others might not be so fortunate, including BeiGene, a company whose Celgene-licensed project happens to be a competitor to the Bristol-owned Opdivo.

Biotech at large is losing its most prolific business development player

No one in biotech doled out deal dollars quite like Celgene. Since 2008, $131 billion was spent by Celgene on acquisitions, partnerships, and licensing deals with smaller biotechs, according to DealForma. That’s more than all the money similarly invested by its big-cap biotech brethren, combined.
With Celgene subsumed, will Bristol’s pockets be as deep? If not, will biotech business development suffer?

The ride isn’t over yet for Celgene shareholders

Among the less-discussed facets of the merger is this: Under the agreement, every Celgene share is worth one share of Bristol, $50 in cash, and one lottery ticket called a CVR. Short for contingent value right, a CVR is a tradable note that entitles its holder to a cash payout if certain futures come true. In Celgene’s case, the cash amounts to $9, and the futures are these: Ozanimod and liso-cel must win FDA approval by the end of 2020, and bb2121 must do so by the end of 2021.
There’s no partial credit, meaning if any of those therapies gets rejected — or approved even one day after its deadline — the CVR is worthless. That makes this a fairly high-stakes proposition for Celgene shareholders. And, notably, the two parties in the deal have different expectations. As analysts at Mizuho pointed out earlier this week, Celgene assigns a roughly 69% probability of success, which gives the CVR a value of about $6, while Bristol believes it has a 45% chance of paying off, making the CVR worth roughly $4.
The CVR will trade on the open market, so we’ll soon find out what the wisdom of the crowd has to say about Celgene’s pipeline.

What’s in a name?

The Bristol-Myers Corp. and Squibb Corp. merged in 1989 to form Bristol-Myers Squibb. There’s been no outward suggestion from Bristol executives that another corporate rebranding is being considered. That’s sort of a shame, because to see the Celgene name, a longtime biotech bellwether, disappear, will feel odd.
Not that anyone’s asking our advice, but Bristol-Celgene Squibb has a nice ring to it. Or, how about Bristol-Myers Celgene? Not bad. Bristol-Myers Celgene Squibb starts to sound a bit too much like a law firm. Bristolgene-Myers Squibb-Cel? Please, no.
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Immunotherapy for neurodegeneration?

Alzheimer’s disease (AD), Parkinson’s disease (PD), and prion diseases such as Creutzfeldt-Jakob disease attack different parts of the central nervous system (CNS) and elicit distinct symptoms, yet they share many biochemical and neuropathological features. These include the formation of protein aggregates in the affected brain regions and progressive activation of non-neuronal cells in the brain that play crucial roles in immune responses. The activation of immune cells in the CNS (“neuroinflammation”) is prominent in these diseases. However, it remains unclear whether boosting or suppressing the immune system, in the brain or in the periphery, may attenuate neurodegeneration. In the case of extraneural prion infections, genetic or pharmacological ablation of components of the immune system, such as B cells and complement, can prevent disease (1). However, immunotherapies, which have been successful in treating certain types of cancer, have yet to reverse neurodegeneration in any patients. Therefore, the therapeutic promise of this approach remains debatable.
Immunotherapy such as immune checkpoint blockade, which enhances the systemic adaptive immune response, may have potential in combating neurodegeneration, especially in AD (2, 3). But recent studies have failed to observe any beneficial effects of immune checkpoint blockade in mouse models of AD (4) and of prion diseases (5, 6), raising questions about the effectiveness of this approach. By contrast, findings from studies of human genetics and experimental models suggest that innate immunity in the brain has pivotal roles in the pathogenesis of neurodegenerative diseases. Therefore, targeting the immune reactions inside the brain may have enormous potential for treating these devastating disorders, yet a clear therapeutic path has not been discerned and well-defined, validated targets are still in demand.
The inhibition of immune checkpoint receptors, an approach to fighting cancers through boosting the adaptive immune system, has revolutionized cancer medicine (and was awarded a Nobel Prize in 2018). Immune checkpoint inhibition is mainly achieved by systemically blocking the activity of negative regulators of T cell activation, such as programmed cell death 1 (PD1), cytotoxic T lymphocyte–associated antigen 4 (CTLA4), and lymphocyte activation gene 3 (LAG3). The expression of these molecules, among others, establishes a state of immune suppression called tolerance toward cells of the body, which underlies the failure of the immune system to clear tumor cells (which are derived from cells of the body). Might systemic immune suppression contribute to the inefficient clearance of pathological protein aggregates in neurodegenerative diseases? Indeed, treatment with PD1-specific antibodies enhanced the infiltration of peripheral myeloid cells into the CNS and reduced the amount of β-amyloid (Aβ) plaques in the hippocampus and cortex (two brain regions most affected in AD) in two transgenic mouse models of AD (2). Moreover, LAG3 was found to facilitate the cell-to-cell spread of α-synuclein in a mouse model of PD (7).
Although PD1-specific antibodies are not harmless and can trigger autoimmunity, repurposing them for treating AD—an untreatable condition—could be justified. However, another study has found no effect of anti-PD1 antibody therapy on myeloid cell infiltration into the brain and Aβ load in these CNS regions in three other AD mouse models (4).
The brain Aβ load does not always correlate with cognitive performance, and the major determinant of cognitive decline is loss of synapses. Therefore, functional recovery tests deserve a high priority when evaluating therapeutic interventions for neurodegenerative diseases. The clearance of Aβ plaques was accompanied by recovery of cognitive performance in some of the anti-PD1 antibody–treated mouse models of AD, although effects on synapse dynamics were not studied (2). In other AD mouse models, however, the effects of anti-PD1 treatment on cognitive function were not investigated (4). Hence, the molecular underpinnings of functional recovery in the successfully treated AD mouse models are still somewhat nebulous (see the figure).
Moreover, immune checkpoint blockade may affect cognition independently of plaque clearance. A plethora of immune modulators, including cytokines, complement components, and histocompatibility proteins, play vital roles in synapse formation, refinement, and excitability, as well as in structural and functional synaptic plasticity during development and in the adult brain (8). Treatment with anti-PD1 antibodies may induce the expression of these immune modulators and their entry into the CNS.
Mouse models of AD poorly represent the human condition. Could immune checkpoint blockade still hold therapeutic value for neurodegenerative diseases? Although there are limited data on how immunotherapy affects the human brain, anecdotal clinical reports yield little reason for optimism. In contrast to mouse models of AD, cognitive deterioration is frequent among patients undergoing cancer treatments, including immunotherapy. Even in preclinical animal tumor models, blocking the immune checkpoint receptor CTLA-4 (combined with radiotherapy) reduced tumor growth but resulted in cognitive impairment (9). In principle, because immune checkpoint blockade enhances the overall ability of the adaptive immune system to target multiple disease-associated factors, one could explore its usefulness in neurodegenerative diseases other than AD.
In prion diseases, however, targeting the immune checkpoint molecules PD1 and LAG3 did not alter prion deposition and the course of disease (5, 6). Moreover, loss of PD1 did not induce myeloid mobilization to prion-infected brains (6). These results again suggest that PD1 inhibition may not suffice to promote the entry of peripheral myeloid cells into the CNS. Therefore, current evidence does not encourage the direct testing of immune checkpoint blockade in patients affected by neurodegenerative diseases. However, the increasing adoption of immune checkpoint inhibition against a growing variety of common cancers will enable statistically powered investigations of the effects of immunotherapy on human brain functions. Similarly, patients are increasingly subjected to anticancer immunotherapy, and some of them are likely to develop neurodegenerative diseases as they age. Analyzing the progression of disease in these patients, including neuropathological assessments of autopsied brains, may provide much-needed answers to these critical questions.
Targeting the innate arm of immunity inside the brain may hold more promise than targeting its adaptive arm through systemic immune checkpoint blockade. Genome-wide association studies of neurodegeneration have revealed correlations of neuroinflammatory genes in these diseases (10). Many biological processes can lead to the activation of astrocytes and microglia (non-neuronal cells in the brain), which in turn can be beneficial or deleterious. Hence, identifying specific pathways for intervention is crucial for the success of therapies targeting non-neuronal cell reactions in neurodegenerative diseases.
Progress in this area may be facilitated by the discovery of inflammasome activation in AD, PD, and other similar diseases such as amyotrophic lateral sclerosis (11–13). Inflammasomes are large complexes that play key roles in innate immune responses and in the maturation and secretion of proinflammatory cytokines such as interleukin-1β (IL-1β). An inflammasome consists of a sensor molecule, such as NLRP3 (NOD, LRR- and pyrin domain-containing 3), the adaptor protein ASC (apoptosis-associated speck-like protein containing CARD), and caspase-1, which together form a functional complex upon infection, tissue damage, or protein misfolding, such as Aβ pathologic aggregation.
In the brains of patients affected by AD and PD, the inflammasome is activated within reactive microglia (11, 12). The cascade of inflammasome activation in these cells leads to the generation of ASC “specks,” large assemblies of ASC protein that can self-propagate (much like prions), driving the neurotoxic inflammatory response and accelerating AD pathology by acting as seeds for further Aβ aggregation (11, 14). In mouse models of AD, genetic inhibition of inflammasome activity reduces not only the Aβ load, but also proinflammatory cytokine production and cognitive impairment (11). Similarly, oral treatment with a small-molecule inhibitor of NLRP3 inflammasome prevented α-synuclein pathology and neurodegeneration in PD mouse models, resulting in improved motor function (12).
Brain inflammation
Immune cells in the brain (microglia) promote inflammation and loss of neural connectivity, whereas other microglia and anti-inflammatory drugs (NSAIDs) counter this degeneration. It is not clear whether immunotherapy can stimulate the infiltration of immune cells and factors into the brain to modulate inflammation, such as in Alzheimer’s disease.
GRAPHIC: C. BICKEL/SCIENCE
Brain inflammation
Immune cells in the brain (microglia) promote inflammation and loss of neural connectivity, whereas other microglia and anti-inflammatory drugs (NSAIDs) counter this degeneration. It is not clear whether immunotherapy can stimulate the infiltration of immune cells and factors into the brain to modulate inflammation, such as in Alzheimer’s disease.
GRAPHIC: C. BICKEL/SCIENCE
Furthermore, several nonsteroidal anti-inflammatory drugs (NSAIDs) of the fenamate class are effective inhibitors of NLRP3 inflammasome activation (15). Treatment with fenamates restored cognitive function in a mouse model of AD (15). These studies have laid a solid foundation for the clinical translation of inflammasome inhibitors and the repurposing of fenamates to treat AD and potentially other forms of neurodegeneration.
Although at first they may seem contradictory, these findings point to neuroinflammation as a driver of AD and possibly of other neurodegenerative conditions. These developments herald a paradigm shift away from the “amyloid cascade” hypothesis, which posits that in neurodegenerative diseases, pathologies stem from protein aggregation. Although nearly all therapeutic attempts are still aimed at quenching protein aggregation, it is increasingly evident that aggregation is only a part of the story. How the pathological accumulation of aggregated proteins affects innate (and perhaps adaptive) immunity, and vice versa, are likely to be addressed by future studies. Identifying the receptor, adaptor, and effector molecules involved in this cross-talk may represent the best path forward to identify therapies that are more effective than those hitherto tested.

References and Notes

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Acknowledgments: A. A. is supported by the European Research Council, the Swiss National Research Foundation, and the Nomis Foundation.
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New York’s mass face recognition trial on drivers has been a spectacular failure

Face recognition proved totally unable to identify the faces of drivers in the city, according to the Wall Street Journal.
The trial: An internal e-mail from the Metropolitan Transportation Authority seen by the WSJ included the details of the trial at the Robert F. Kennedy Bridge last year. Cameras attached to the bridge were supposed to capture and identify the faces of drivers through their windshields as they passed, matching them against government databases.
The results: But the document, from November of last year, says that the “initial period for the proof of concept testing at the RFK for facial recognition has been completed and failed with no faces (0%) being detected within acceptable parameters.” That’s no faces accurately identified. Oops. Despite the failure, more cameras are going to be positioned on other bridges and tunnels, according to a spokesperson.
Controversy: Face recognition is rightly controversial. As well as its potential as a tool for mass surveillance, it has been shown to misidentify non-white faces and women. Last week a letter by prominent AI researchers called on Amazon to stop selling its face recognition software to law enforcement. Lee Rowland, policy director at the New York Civil Liberties Union, told the WSJ that face recognition coupled with the gathering of drivers’ licence plate data “represents a sea change in our government’s ability to track us.”
Apart from that, the failure of the NYC trial so far also suggests that the technology is perhaps not quite as game-ready as some of its more bullish advocates would suggest.
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