This Week in Apps: App Store bill passes AZ House, ‘deep nostalgia’ goes viral, Twitter Spaces arrives on Android
Welcome back to This Week in Apps, the weekly TechCrunch series that recaps the latest in mobile OS news, mobile applications and the overall app economy. The app industry is as hot as ever, with a record 218 billion downloads and $143 billion in…
Welcome back to This Week in Apps, the weekly TechCrunch series that recaps the latest in mobile OS news, mobile applications and the overall app economy.
The app industry is as hot as ever, with a record 218 billion downloads and $143 billion in global consumer spend in 2020.
Consumers last year also spent 3.5 trillion minutes using apps on Android devices alone. And in the U.S., app usage surged ahead of the time spent watching live TV. Currently, the average American watches 3.7 hours of live TV per day, but now spends four hours per day on their mobile devices.
Apps aren’t just a way to pass idle hours — they’re also a big business. In 2019, mobile-first companies had a combined $544 billion valuation, 6.5x higher than those without a mobile focus. In 2020, investors poured $73 billion in capital into mobile companies — a figure that’s up 27% year-over-year.
This week we’re looking into the app store bill in Arizona, the trend of animating family photos and what’s next for Twitter’s Clubhouse rival, among other things.
Arizona House passes a bill that would allow developers to avoid the “Apple tax”
Image Credits: Apple
The Arizona House of Representatives this week passed a bill (HB 2005) that could significantly impact Apple and Google’s grip on the App Store market. Unlike a similar measure recently shot down by the North Dakota Senate, this new bill doesn’t force app stores to offer alternative ways for developers to distribute their apps. Instead, it focuses on giving developers the right to use third-party systems that would allow them to circumvent the 15%-20% cut that Apple and Google take from app sales, in-app purchases and subscriptions.
Apple and Google lobbyists were already fighting against this bill before it was even formally introduced by Arizona State Rep. Regina Cobb. Cobb says she was approached by a lobbyist representing Match Group and the Coalition for App Fairness (CAF) — the latter, which has organized some of Apple’s largest competitors — like Epic Games, Match Group, Spotify and Tile — to fight back against Apple’s control of the app ecosystem.
Some legislators may oppose the bill on the grounds that these decisions are more of a federal matter and concerns over how the state would be able to enforce such a policy. The Arizona bill still has to make it through the Senate (and could be vetoed by Governor Doug Ducey) in order to become a law. If it did pass, it would make Arizona an attractive place to set up an app business and could set the groundwork for other states to pass similar legislation.
Animated family photos top the App Store
#MyHeritage re-animated my grandma Anny (here 16 years old in 1936) and now I'm crying tears of joy, hope, thankfulness, longing & regrets pic.twitter.com/uXtjBz2UZV
MyHeritage’s recently launched update that lets users animate their old photos helped to send the app to the top of the App Store this week. The company had last week introduced “Deep Nostalgia” — a facial animation feature powered by technology from Israeli tech company (and TechCrunch Battlefield alum) D-ID. To animate the photos, the tech maps the facial features from the photo to a driver video to create what it calls a “live portrait.”
The app went viral on social media, including TikTok, as people used the photo to animate long-ago relatives and other historical figures.
But in a number of more touching videos, people film themselves reacting to seeing their mom or dad “come to life” again through the tech, blinking, smiling and nodding, often set to “Remember When” by Alan Jackson or “Sign of the Times” by Harry Styles as the background track.
Though MyHeritage shot up to become the No. 1 Overall app on the App Store as of Tuesday, a smaller startup, Rosebud, quietly pivoted to address the same use case with its TokkingHeads app. The app, founded by Berkeley PhD Lisha Li, was originally intended for making funny videos and memes with friends, video game avatars or celebs by animating portrait photos with text, speech and puppetry via video — but not so well that it would cross into “deepfake” territory.
But after the release of MyHeritage’s update, TokkingHeads quickly updated to alert users to its own feature set, while also elevating the MyHeritage-like animations it offers in the app. As a result, the app started to gain a following of its own. On February 28, 2021, TokkingHeads saw 1,000 downloads. The next day, it had 8,000 downloads. The following two days, March 2 and 3, it saw 24,000 downloads and 28,000 downloads, respectively.
The app has since reached as high as No. 12 in the App Store’s Entertainment category, as of the time of writing, and No. 94 Overall. (And was climbing daily.)
The YC-backed startup’s ambitions extend beyond animated photos, however. It’s been developing internal tools which it used to generate backgrounds and visuals for use in personalized media. It’s been testing these tools with personalized meditation videos on TikTok, but isn’t yet ready to fully announce a new product. Rosebud is backed by $2.2 million in seed funding led by Khosla Ventures, with participation from Twitch COO Kevin Lin, OpenAI co-founder Ilya Sutskever, former Coinbase CTO Balaji Srinivasan and others.
Weekly News
Platforms: Apple
Image Credits: TechCrunch
Apple clarifies you can’t actually set a “default” music service in iOS 14.5. It explains that the Siri feature that asks you how you want to play the music or other audio (like podcasts or audiobooks) that you’ve requested is only an example of Siri Intelligence, and is not technically making that service a “default.”
Apple’s courtroom battle with Epic Games over the App Store’s alleged anti-competitive behavior is set to start May 3. The judge believes the case is significant enough to hold an in-person trial with witnesses.
The U.K.’s anti-competition authority, CMA (Competition and Markets Authority) is opening its own investigation into Apple’s App Store, following a number of complaints from developers alleging unfair terms.
Apple releases iOS 14.5 beta 3.The new release adds a notification banner to iPhone if you have your Apple Watch set to unlock your paired phone; brings back the Siri feature to choose your preferred audio app for certain requests; updates the Find My screen with plans to support accessories; and makes reference to Apple Card Family features, among other things.
In a bit of App Store history revealed this week, Apple’s Scott Forstall once told Pandora to use jailbroken iPhones to develop their music app ahead of the App Store’s launch.
Apple shuts down Buddybuild, the app development service it acquired in 2018. The team had joined the Xcode group at Apple, but Buddybuild remained online for existing customers. An email has now informed those customers it will cease operations on March 31, 2021.
Apple’s upcoming AirTags gains an anti-stalking feature. In the latest iOS 14.5 beta, a new “Item Safety Features” option was found to be on by default. It would warn you if someone secretly hid an AirTag in your possessions.
Something I hadn’t considered before: new beta includes a Item Safety setting in Find My. This is how Apple is trying to prevent 'stalking' with AirTags. If someone secretly hides a tag in your possessions, your phone will notice and warn you about it. pic.twitter.com/NVJyAZlthw
Google Play announced it’s reducing the minimum price limit for products in over 20 markets across Latin America, EMEA and APAC. In these markets, developers can now set prices in the range of 10-30 cents U.S. equivalent — or “sub dollar” prices. Google says this will allow developers to reach new potential buyers.
Image Credits: Google
Google debuted Flutter 2, an upgrade that broadens Flutter from a mobile framework to a portable framework. Flutter 2 will allow developers to ship native apps across iOS, Android, Windows, macOS and Linux, as well as web experiences for Chrome, Safari, Firefox and Edge, and cars, TVs and smart TVs. Google says there are now more than 150,000 Flutter apps on the Play Store today, including WeChat, Grab, Yandex Go, Sonos, Betterment and others.
The Google Play Console added a new suite of metrics and comparison benchmarks that will allow developers to evaluate the app’s engagement and monetization against up to 250 different peer sets.
E-commerce
Twitter tests new e-commerce features for tweets. The company was spotted testing a different style of organic tweet which includes product info, pricing and a big “Shop” button. The company confirmed it’s one of many commerce tests in the works.
Amazon’s mobile app got a new icon…again. Customers complained the first iteration, which featured Amazon’s smiling arrow across a brown box with a piece of blue tape at the top, reminded them of Hitler. The updated look gives the tape a smooth edge.
The Google Play Service for AR app, which delivers ARCore updates to Android phones, was updated to include support for dual cameras instead of just one, as before. The change was spotted by Android Police, which noted that the support would arrive on Pixel 4 devices first.
Fintech
More evidence of Apple Card Family support spotted in iOS 14.5 beta 3. The new feature will allow family members to share the same Apple Card through iCloud Family Sharing, so each member can access the card in the Wallet app.
Social
Image Credits: TechCrunch
Twitter Spaces beat Clubhouse to Android. Twitter’s social audio service and Clubhouse rival, Twitter Spaces, has been iterating at a rapid pace. The company has been sharing features in public as they’re designed and prototyped, including titles and descriptions, scheduling options, support for co-hosts and moderators, guest lists and more. Twitter also updated the preview card that appears in the timeline and relabeled its “captions” feature to be more accurate, from an accessibility standpoint. This fast pace of development allowed the new product to reach Android users this week, ahead of Clubhouse. However, Android users can only join Spaces for the time being, they can’t host them. Still, the move will help to serve the pent-up demand for social audio among a huge chunk of the mobile market.
LinkedIn says it will stop using IDFA ahead of the iOS App Tracking Transparency launch. The business social network is getting ahead of the change and says it will instead leverage “first-party data” to help advertisers.
Instagram accidentally hid “likes” for a number of users in the U.S., who were unintentionally added to the ongoing test where likes are no longer displayed. The company attributed this to a bug and said it was fixing the issue ASAP.
Right-wing social app Parler had dropped its lawsuit against AWS to get its cloud hosting services reinstated, but its fight isn’t over yet. In a new case, Parler is now going after Amazon with more charges, including defamation, negligence and breach of contract. The suit claims Parler lost “tens of millions” of users and future users” as well as “hundreds of millions” in revenue.
TikTok adds a Business Profile section for marketers and brands. The section offers marketing tips, insights on app usage and advertising events — and likely, in the future, e-commerce tools.
TikTok forms a Safety Advisory Council in Europe, following the death of a girl who fatally attempted the blackout challenge she saw on the app, leading to emergency intervention by Italy’s data protection authority.
Instagram launches “Live Rooms” for live broadcasts with up to four creators. Previously only two people could go live. The launch has a bit of Clubhouse envy to it, as Instagram notes it could be used for things like talk shows, Q&As and interviews, for example. A similar feature has been spotted in TikTok in recent weeks, as well.
Facebook launched BARS, a TikTok-like app for creating and sharing raps. In the app, users react with “fire” emoji while flipping through a full-screen, vertical video feed of people’s raps.
TikTok launches TikTok Q&A. The new feature will allow creators to respond to viewer questions with either text or video replies, including during livestreams. The questions and answers will also be organized in a new Q&A page, linked from the bio. The feature is a direct response to how many creators were already using the app to interact with fans.
Image Credits: TikTok
Photos
Apple introduced a service that will allow iCloud users to transfer their photos and videos to Google Photos. Anti-competitive scrutiny cracks the walled garden, it seems.
MyHeritage tops the App Store after launching a new feature called Deep Nostalgia that animates users’ old family photos.
Messaging & Communications
WhatsApp brought voice and video calls to the desktop companion app. The calls are end-to-end encrypted, and will later expand to include group calls.
WeChat updates its emojis to dial down the violence. It removed the cigar from the smoking soldier emoji and removed the blood from the meat cleaver emoji. It also no longer shows a hammer hitting a head — it’s now a frying pan.
Streaming & Entertainment
Image Credits: Netflix
Netflix launches “Fast Laughs,” a TikTok-like feed of funny videos. The mobile feature is currently iOS-only and lets users flip through a full-screen vertical video feed with short clips from Netflix programming, react, share and add items to a watchlist or immediately start streaming.
Apple pulls Music Memos, a music creation tool, from the App Store. The app was used to analyze rhythm and chords from acoustic guitar and piano recordings. The company advised users to export their content to Voice Memos library instead.
Hulu brings back picture-in-picture mode with the latest iOS update. The feature had been available previously, but was pulled so Hulu could make refinements.
Spotify’s podcast listeners in the U.S. expected to top Apple Podcasts for the first time in 2021, at 28.2 million listeners on Spotify versus 28 million on Apple Podcasts.
Gaming
Image Credits: Genshin Impact (via Sensor Tower)
Genshin Impact from miHoYo has reached $874 million in consumer spend since its September 2020 launch, reports Sensor Tower, making it already the world’s third-highest-earning mobile game.
Hypercasual games are now the largest genre for game downloads, a separate Sensor Tower report says. The genre has expanded from a 17% share of downloads in 2017 to now 31% in 2020. Other genres seeing growth include Arcade and Puzzle, increasing by 33% and 78% respectively.
Books and Reading
Flipboard expands its local coverage to over 1,000 cities and towns. The company last year launched a broader initiative around local news, allowing users to follow their local publications, TV stations, blogs and more.
Google Play Books was updated with new tools for younger readers, including “Read & Listen,” which will let kids listen to a book read out loud, “Tap to Read” to hear words spoken out loud and a kid-friendly dictionary.
Health & Fitness
COVID-19 exposure notification apps have still not seen widespread adoption, USA Today reports. Fewer than half of U.S. states offer the contact-tracing apps, and most people in participating states don’t use them.
Amazon Halo users, the app-paired health and fitness tracker from the retail giant, is being integrated with Alexa. The new feature will let you ask Echo and other Alexa devices for health stats.
Best Buy Health partnered with the Lively app to offer a range of health and safety services aimed at older adults on Apple Watch. Apple Watch users can use the app to get emergency and non-emergency assistance from the Lively agents and receive additional protection from things like Fall Detection.
Period tracking app Clue gets FDA clearance to launch a digital contraceptive. The app’s algorithmic prediction is based on Bayesian modeling and can display the days where there’s a higher risk of pregnancy.
Jamaica’s JamCOVID mobile app and website were taken offline following their third security lapse. The platform was exposing quarantine orders on over than half a million travelers.
Productivity
Image Credits: App Annie
Business and productivity apps reached 7.1 billion downloads in 2020, up 35% YoY, reports App Annie. The jump was attributed to the pandemic, with the biggest surge coming in mid-March when shelter-in-place orders kicked in.
Microsoft pulled the Delve mobile apps from the App Store and Google Play, which will be followed by a full shutdown of the service in June. Delve was designed to surface relevant info and insights using the Office Graph. Users were redirected to Outlook Mobile, which has some similar features.
Microsoft launched Group Transcribe, a new kind of mobile transcription app for in-person meetings. The app requires all meeting participants to record from their own phones, which improves accuracy and speaker identification. It also offers real-time translations to help non-native speakers follow along.
Thousands of Android and iOS app are leaking data from the cloud, Wired reports. In analysis run on more than 1.3 million Android and iOS apps, researchers found almost 84,000 Android apps and nearly 47,000 iOS apps used public cloud services. Of those, misconfigurations were found in 14% — 11,877 Android apps and 6,608 iOS apps — which were exposing personal information, passwords and medical information.
Hackers released a new jailbreak tool for almost every iPhone by using the same vulnerability Apple said last month was under active attack by hackers. The jailbreak, released by the Unc0ver team, works on iOS 11 to iOS 14.3, and iPhone 5s and later.
Google’s apps with privacy labels have begun receiving updates after lengthy pause. Apps that have started to get updates include Gmail, Slides, Docs, Sheets, Calendar, YouTube, YouTube TV, YouTube Music, Google Tasks and Google Podcasts. Google’s key apps still missing labels include Search, Photos, Assistant, Maps, Pay and Chrome.
Funding and M&A
Stream raised $38 million for its service that lets developers build chat and activity feeds into apps with a few lines of code. The company now powers communications for 1 billion users, including in apps like TaskRabbit, NBC Sports, Delivery Hero, Gojek and others.
Whatnot raised $20 million in Series A funding for its livestreaming platform for selling collectible toys and cards. The round was led by a16z, and follows a $4 million seed raised at the end of 2020.
Snapcommerce raised $85 million for its platform that uses messaging to personalize the mobile shopping experience. Inovia Capital and Lion Capital co-led the new growth round, bringing the startup’s total raise to date to $100 million.
Food delivery app Instacart raised $265 million at a $39 billion valuation. The round was raised from existing investors, including Andreessen Horowitz, Sequoia Capital, D1 Capital Partners and others and pushes the valuation up from $17.7 billion in October 2020.
Okta acquired cloud identity startup Auth0 for $6.5 billion. Auth0 offers authentication and security for apps across native mobile, desktop, and web apps. Following the deal, Auth0 will continue to operate as an independent unit inside Okta.
Fintech Square acquired Jay-Z’s streaming service TIDAL for $297 million. Perhaps those yachting trips paid off? Square plans to offer financial tools to artists to help them collect revenue. Despite the deal’s seeming oddness, a good bet is that Square plans to expand into music-based NFTs.
App marketing company AppLovin filed its S-1 ahead of its IPO. The company was valued at $2 billion in 2018, but posted a net loss of $125.9 million in 2020 on revenue of $1.45 billion, up 46% YoY. The company warned investors that it may be impacted by Apple’s IDFA changes.
Maestro raised $15 million for its interactive commerce, community and engagement tools for livestreams across web and mobile. Maestro can also be embedded into native mobile apps using a web view.
Indie weather app Weather Line acquired. The company didn’t provide any details on its acquisition, including the buyer, but said the app will be removed from the App Store. Existing users will continue to have access until April 1, 2022.
Indian jobs app Apna raised $12.5 million in a round led by Sequoia Capital India and Greenoaks Capital. The app is now used by 80,000 employers and 6 million+ workers such as drivers, delivery personnel, electricians and beauticians.
Istanbul’s Dream Games raised $50 million and launched its first mobile gaming title, Royal Match. The round, led by Index Ventures, is the largest Series A raised by a startup in Turkey.
Downloads
West Tenth
Image Credits: West Tenth
West Tenth’s new app aims to give local home-based business owners a platform to reach potential clients and make sales. The app focuses on women who have opted out of the traditional workforce to stay home, often to raise kids and work more flexible hours. Often targeted by predatory MLMs, West Tenth aims to convince women that many of their everyday skills are, in fact, marketable businesses — like cooking and meal prep, party planning, interior design, photography, home organization, baby sleep training, fitness instructions, homemade crafts and more. The startup also offers online education classes to teach women the basics of marketing and running a home business. (iOS and Android)
Social audio is growing in popularity thanks to apps like Clubhouse and Twitter’s Spaces. A startup called Cappuccino, reviewed here by TechCrunch, now wants to bring social audio to a more intimate setting: groups of friends. The anti-Clubhouse app lets friends record “podcasts,” which are designed for private consumption. (iOS and Android)
If you had any doubts at all about the Wild Wild West that are App Store ratings & reviews, someone is currently buying fake 5-star reviews for my own FlickType app – presumably so that Apple will take my app down.
In his interview with CNBC and New York Times journalist Andrew Ross Sorkin, Bill Gates said “I actually use an Android phone. I’ll often play around with iPhones, but the one I carry around happens to be Android. pic.twitter.com/bpX6aTl9nf
Chronic stress and inflammation linked to societal and environmental impacts in new study
From anxiety about the state of the world to ongoing waves of Covid-19, the stresses we face can seem relentless and even overwhelming. Worse, these stressors…
From anxiety about the state of the world to ongoing waves of Covid-19, the stresses we face can seem relentless and even overwhelming. Worse, these stressors can cause chronic inflammation in our bodies. Chronic inflammation is linked to serious conditions such as cardiovascular disease and cancer – and may also affect our thinking and behavior.
Credit: Image: Vodovotz et al/Frontiers
From anxiety about the state of the world to ongoing waves of Covid-19, the stresses we face can seem relentless and even overwhelming. Worse, these stressors can cause chronic inflammation in our bodies. Chronic inflammation is linked to serious conditions such as cardiovascular disease and cancer – and may also affect our thinking and behavior.
A new hypothesis published in Frontiers in Science suggests the negative impacts may extend far further.
“We propose that stress, inflammation, and consequently impaired cognition in individuals can scale up to communities and populations,” explained lead author Prof Yoram Vodovotz of the University of Pittsburgh, USA.
“This could affect the decision-making and behavior of entire societies, impair our cognitive ability to address complex issues like climate change, social unrest, and infectious disease – and ultimately lead to a self-sustaining cycle of societal dysfunction and environmental degradation,” he added.
Bodily inflammation ‘mapped’ in the brain
One central premise to the hypothesis is an association between chronic inflammation and cognitive dysfunction.
“The cause of this well-known phenomenon is not currently known,” said Vodovotz. “We propose a mechanism, which we call the ‘central inflammation map’.”
The authors’ novel idea is that the brain creates its own copy of bodily inflammation. Normally, this inflammation map allows the brain to manage the inflammatory response and promote healing.
When inflammation is high or chronic, however, the response goes awry and can damage healthy tissues and organs. The authors suggest the inflammation map could similarly harm the brain and impair cognition, emotion, and behavior.
Accelerated spread of stress and inflammation online
A second premise is the spread of chronic inflammation from individuals to populations.
“While inflammation is not contagious per se, it could still spread via the transmission of stress among people,” explained Vodovotz.
The authors further suggest that stress is being transmitted faster than ever before, through social media and other digital communications.
“People are constantly bombarded with high levels of distressing information, be it the news, negative online comments, or a feeling of inadequacy when viewing social media feeds,” said Vodovotz. “We hypothesize that this new dimension of human experience, from which it is difficult to escape, is driving stress, chronic inflammation, and cognitive impairment across global societies.”
Inflammation as a driver of social and planetary disruption
These ideas shift our view of inflammation as a biological process restricted to an individual. Instead, the authors see it as a multiscale process linking molecular, cellular, and physiological interactions in each of us to altered decision-making and behavior in populations – and ultimately to large-scale societal and environmental impacts.
“Stress-impaired judgment could explain the chaotic and counter-intuitive responses of large parts of the global population to stressful events such as climate change and the Covid-19 pandemic,” explained Vodovotz.
“An inability to address these and other stressors may propagate a self-fulfilling sense of pervasive danger, causing further stress, inflammation, and impaired cognition in a runaway, positive feedback loop,” he added.
The fact that current levels of global stress have not led to widespread societal disorder could indicate an equally strong stabilizing effect from “controllers” such as trust in laws, science, and multinational organizations like the United Nations.
“However, societal norms and institutions are increasingly being questioned, at times rightly so as relics of a foregone era,” said Prof Paul Verschure of Radboud University, the Netherlands, and a co-author of the article. “The challenge today is how we can ward off a new adversarial era of instability due to global stress caused by a multi-scale combination of geopolitical fragmentation, conflicts, and ecological collapse amplified by existential angst, cognitive overload, and runaway disinformation.”
Reducing social media exposure as part of the solution
The authors developed a mathematical model to test their ideas and explore ways to reduce stress and build resilience.
“Preliminary results highlight the need for interventions at multiple levels and scales,” commented co-author Prof Julia Arciero of Indiana University, USA.
“While anti-inflammatory drugs are sometimes used to treat medical conditions associated with inflammation, we do not believe these are the whole answer for individuals,” said Dr David Katz, co-author and a specialist in preventive and lifestyle medicine based in the US. “Lifestyle changes such as healthy nutrition, exercise, and reducing exposure to stressful online content could also be important.”
“The dawning new era of precision and personalized therapeutics could also offer enormous potential,” he added.
At the societal level, the authors suggest creating calm public spaces and providing education on the norms and institutions that keep our societies stable and functioning.
“While our ‘inflammation map’ hypothesis and corresponding mathematical model are a start, a coordinated and interdisciplinary research effort is needed to define interventions that would improve the lives of individuals and the resilience of communities to stress. We hope our article stimulates scientists around the world to take up this challenge,” Vodovotz concluded.
The article is part of the Frontiers in Science multimedia article hub ‘A multiscale map of inflammatory stress’. The hub features a video, an explainer, a version of the article written for kids, and an editorial, viewpoints, and policy outlook from other eminent experts: Prof David Almeida (Penn State University, USA), Prof Pietro Ghezzi (University of Urbino Carlo Bo, Italy), and Dr Ioannis P Androulakis (Rutgers, The State University of New Jersey, USA).
Journal
Frontiers in Science
DOI
10.3389/1239462
Method of Research
Computational simulation/modeling
Subject of Research
Not applicable
Article Title
A multiscale inflammatory map: linking individual stress to societal dysfunction
Article Publication Date
12-Mar-2024
COI Statement
YV is a cofounder of, and stakeholder in, Immunetrics, Inc. and a consultant to Anuna AI. PFMJV is the founder of, and stakeholder in, Eodyne Systems s.l. and Sapiens5 Holding BV. DLK was employed by Tangelo – Intend, Inc. Neither these companies nor the funders mentioned above were involved in the study design, data collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. The companies mentioned above also did not provide funding for the study. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors YV and PV declared that they are editorial board members of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
Acadia’s Nuplazid fails PhIII study due to higher-than-expected placebo effect
After years of trying to expand the market territory for Nuplazid, Acadia Pharmaceuticals might have hit a dead end, with a Phase III fail in schizophrenia…
After years of trying to expand the market territory for Nuplazid, Acadia Pharmaceuticals might have hit a dead end, with a Phase III fail in schizophrenia due to the placebo arm performing better than expected.
Steve Davis
“We will continue to analyze these data with our scientific advisors, but we do not intend to conduct any further clinical trials with pimavanserin,” CEO Steve Davis said in a Monday press release. Acadia’s stock $ACAD dropped by 17.41% before the market opened Tuesday.
Pimavanserin, a serotonin inverse agonist and also a 5-HT2A receptor antagonist, is already in the market with the brand name Nuplazid for Parkinson’s disease psychosis. Efforts to expand into other indications such as Alzheimer’s-related psychosis and major depression have been unsuccessful, and previous trials in schizophrenia have yielded mixed data at best. Its February presentation does not list other pimavanserin studies in progress.
The Phase III ADVANCE-2 trial investigated 34 mg pimavanserin versus placebo in 454 patients who have negative symptoms of schizophrenia. The study used the negative symptom assessment-16 (NSA-16) total score as a primary endpoint and followed participants up to week 26. Study participants have control of positive symptoms due to antipsychotic therapies.
The company said that the change from baseline in this measure for the treatment arm was similar between the Phase II ADVANCE-1 study and ADVANCE-2 at -11.6 and -11.8, respectively. However, the placebo was higher in ADVANCE-2 at -11.1, when this was -8.5 in ADVANCE-1. The p-value in ADVANCE-2 was 0.4825.
In July last year, another Phase III schizophrenia trial — by Sumitomo and Otsuka — also reported negative results due to what the company noted as Covid-19 induced placebo effect.
According to Mizuho Securities analysts, ADVANCE-2 data were disappointing considering the company applied what it learned from ADVANCE-1, such as recruiting patients outside the US to alleviate a high placebo effect. The Phase III recruited participants in Argentina and Europe.
Analysts at Cowen added that the placebo effect has been a “notorious headwind” in US-based trials, which appears to “now extend” to ex-US studies. But they also noted ADVANCE-1 reported a “modest effect” from the drug anyway.
Nonetheless, pimavanserin’s safety profile in the late-stage study “was consistent with previous clinical trials,” with the drug having an adverse event rate of 30.4% versus 40.3% with placebo, the company said. Back in 2018, even with the FDA approval for Parkinson’s psychosis, there was an intense spotlight on Nuplazid’s safety profile.
Acadia previously aimed to get Nuplazid approved for Alzheimer’s-related psychosis but had many hurdles. The drug faced an adcomm in June 2022 that voted 9-3 noting that the drug is unlikely to be effective in this setting, culminating in a CRL a few months later.
As for the company’s next R&D milestones, Mizuho analysts said it won’t be anytime soon: There is the Phase III study for ACP-101 in Prader-Willi syndrome with data expected late next year and a Phase II trial for ACP-204 in Alzheimer’s disease psychosis with results anticipated in 2026.
Acadia collected $549.2 million in full-year 2023 revenues for Nuplazid, with $143.9 million in the fourth quarter.
"Beware the Ides of March,” Shakespeare quotes the soothsayer’s warning Julius Caesar about what turned out to be an impending assassination on March 15. The death of American liberty happened around the same time four years ago, when the orders went out from all levels of government to close all indoor and outdoor venues where people gather.
It was not quite a law and it was never voted on by anyone. Seemingly out of nowhere, people who the public had largely ignored, the public health bureaucrats, all united to tell the executives in charge – mayors, governors, and the president – that the only way to deal with a respiratory virus was to scrap freedom and the Bill of Rights.
And they did, not only in the US but all over the world.
The forced closures in the US began on March 6 when the mayor of Austin, Texas, announced the shutdown of the technology and arts festival South by Southwest. Hundreds of thousands of contracts, of attendees and vendors, were instantly scrapped. The mayor said he was acting on the advice of his health experts and they in turn pointed to the CDC, which in turn pointed to the World Health Organization, which in turn pointed to member states and so on.
There was no record of Covid in Austin, Texas, that day but they were sure they were doing their part to stop the spread. It was the first deployment of the “Zero Covid” strategy that became, for a time, official US policy, just as in China.
It was never clear precisely who to blame or who would take responsibility, legal or otherwise.
This Friday evening press conference in Austin was just the beginning. By the next Thursday evening, the lockdown mania reached a full crescendo. Donald Trump went on nationwide television to announce that everything was under control but that he was stopping all travel in and out of US borders, from Europe, the UK, Australia, and New Zealand. American citizens would need to return by Monday or be stuck.
Americans abroad panicked while spending on tickets home and crowded into international airports with waits up to 8 hours standing shoulder to shoulder. It was the first clear sign: there would be no consistency in the deployment of these edicts.
There is no historical record of any American president ever issuing global travel restrictions like this without a declaration of war. Until then, and since the age of travel began, every American had taken it for granted that he could buy a ticket and board a plane. That was no longer possible. Very quickly it became even difficult to travel state to state, as most states eventually implemented a two-week quarantine rule.
The next day, Friday March 13, Broadway closed and New York City began to empty out as any residents who could went to summer homes or out of state.
On that day, the Trump administration declared the national emergency by invoking the Stafford Act which triggers new powers and resources to the Federal Emergency Management Administration.
In addition, the Department of Health and Human Services issued a classified document, only to be released to the public months later. The document initiated the lockdowns. It still does not exist on any government website.
The White House Coronavirus Response Task Force, led by the Vice President, will coordinate a whole-of-government approach, including governors, state and local officials, and members of Congress, to develop the best options for the safety, well-being, and health of the American people. HHS is the LFA [Lead Federal Agency] for coordinating the federal response to COVID-19.
Closures were guaranteed:
Recommend significantly limiting public gatherings and cancellation of almost all sporting events, performances, and public and private meetings that cannot be convened by phone. Consider school closures. Issue widespread ‘stay at home’ directives for public and private organizations, with nearly 100% telework for some, although critical public services and infrastructure may need to retain skeleton crews. Law enforcement could shift to focus more on crime prevention, as routine monitoring of storefronts could be important.
In this vision of turnkey totalitarian control of society, the vaccine was pre-approved: “Partner with pharmaceutical industry to produce anti-virals and vaccine.”
The National Security Council was put in charge of policy making. The CDC was just the marketing operation. That’s why it felt like martial law. Without using those words, that’s what was being declared. It even urged information management, with censorship strongly implied.
The timing here is fascinating. This document came out on a Friday. But according to every autobiographical account – from Mike Pence and Scott Gottlieb to Deborah Birx and Jared Kushner – the gathered team did not meet with Trump himself until the weekend of the 14th and 15th, Saturday and Sunday.
According to their account, this was his first real encounter with the urge that he lock down the whole country. He reluctantly agreed to 15 days to flatten the curve. He announced this on Monday the 16th with the famous line: “All public and private venues where people gather should be closed.”
This makes no sense. The decision had already been made and all enabling documents were already in circulation.
There are only two possibilities.
One: the Department of Homeland Security issued this March 13 HHS document without Trump’s knowledge or authority. That seems unlikely.
Two: Kushner, Birx, Pence, and Gottlieb are lying. They decided on a story and they are sticking to it.
Trump himself has never explained the timeline or precisely when he decided to greenlight the lockdowns. To this day, he avoids the issue beyond his constant claim that he doesn’t get enough credit for his handling of the pandemic.
With Nixon, the famous question was always what did he know and when did he know it? When it comes to Trump and insofar as concerns Covid lockdowns – unlike the fake allegations of collusion with Russia – we have no investigations. To this day, no one in the corporate media seems even slightly interested in why, how, or when human rights got abolished by bureaucratic edict.
As part of the lockdowns, the Cybersecurity and Infrastructure Security Agency, which was and is part of the Department of Homeland Security, as set up in 2018, broke the entire American labor force into essential and nonessential.
They also set up and enforced censorship protocols, which is why it seemed like so few objected. In addition, CISA was tasked with overseeing mail-in ballots.
Only 8 days into the 15, Trump announced that he wanted to open the country by Easter, which was on April 12. His announcement on March 24 was treated as outrageous and irresponsible by the national press but keep in mind: Easter would already take us beyond the initial two-week lockdown. What seemed to be an opening was an extension of closing.
This announcement by Trump encouraged Birx and Fauci to ask for an additional 30 days of lockdown, which Trump granted. Even on April 23, Trump told Georgia and Florida, which had made noises about reopening, that “It’s too soon.” He publicly fought with the governor of Georgia, who was first to open his state.
Before the 15 days was over, Congress passed and the president signed the 880-page CARES Act, which authorized the distribution of $2 trillion to states, businesses, and individuals, thus guaranteeing that lockdowns would continue for the duration.
There was never a stated exit plan beyond Birx’s public statements that she wanted zero cases of Covid in the country. That was never going to happen. It is very likely that the virus had already been circulating in the US and Canada from October 2019. A famous seroprevalence study by Jay Bhattacharya came out in May 2020 discerning that infections and immunity were already widespread in the California county they examined.
What that implied was two crucial points: there was zero hope for the Zero Covid mission and this pandemic would end as they all did, through endemicity via exposure, not from a vaccine as such. That was certainly not the message that was being broadcast from Washington. The growing sense at the time was that we all had to sit tight and just wait for the inoculation on which pharmaceutical companies were working.
By summer 2020, you recall what happened. A restless generation of kids fed up with this stay-at-home nonsense seized on the opportunity to protest racial injustice in the killing of George Floyd. Public health officials approved of these gatherings – unlike protests against lockdowns – on grounds that racism was a virus even more serious than Covid. Some of these protests got out of hand and became violent and destructive.
Meanwhile, substance abuse rage – the liquor and weed stores never closed – and immune systems were being degraded by lack of normal exposure, exactly as the Bakersfield doctors had predicted. Millions of small businesses had closed. The learning losses from school closures were mounting, as it turned out that Zoom school was near worthless.
It was about this time that Trump seemed to figure out – thanks to the wise council of Dr. Scott Atlas – that he had been played and started urging states to reopen. But it was strange: he seemed to be less in the position of being a president in charge and more of a public pundit, Tweeting out his wishes until his account was banned. He was unable to put the worms back in the can that he had approved opening.
By that time, and by all accounts, Trump was convinced that the whole effort was a mistake, that he had been trolled into wrecking the country he promised to make great. It was too late. Mail-in ballots had been widely approved, the country was in shambles, the media and public health bureaucrats were ruling the airwaves, and his final months of the campaign failed even to come to grips with the reality on the ground.
At the time, many people had predicted that once Biden took office and the vaccine was released, Covid would be declared to have been beaten. But that didn’t happen and mainly for one reason: resistance to the vaccine was more intense than anyone had predicted. The Biden administration attempted to impose mandates on the entire US workforce. Thanks to a Supreme Court ruling, that effort was thwarted but not before HR departments around the country had already implemented them.
As the months rolled on – and four major cities closed all public accommodations to the unvaccinated, who were being demonized for prolonging the pandemic – it became clear that the vaccine could not and would not stop infection or transmission, which means that this shot could not be classified as a public health benefit. Even as a private benefit, the evidence was mixed. Any protection it provided was short-lived and reports of vaccine injury began to mount. Even now, we cannot gain full clarity on the scale of the problem because essential data and documentation remains classified.
After four years, we find ourselves in a strange position. We still do not know precisely what unfolded in mid-March 2020: who made what decisions, when, and why. There has been no serious attempt at any high level to provide a clear accounting much less assign blame.
Not even Tucker Carlson, who reportedly played a crucial role in getting Trump to panic over the virus, will tell us the source of his own information or what his source told him. There have been a series of valuable hearings in the House and Senate but they have received little to no press attention, and none have focus on the lockdown orders themselves.
The prevailing attitude in public life is just to forget the whole thing. And yet we live now in a country very different from the one we inhabited five years ago. Our media is captured. Social media is widely censored in violation of the First Amendment, a problem being taken up by the Supreme Court this month with no certainty of the outcome. The administrative state that seized control has not given up power. Crime has been normalized. Art and music institutions are on the rocks. Public trust in all official institutions is at rock bottom. We don’t even know if we can trust the elections anymore.
In the early days of lockdown, Henry Kissinger warned that if the mitigation plan does not go well, the world will find itself set “on fire.” He died in 2023. Meanwhile, the world is indeed on fire. The essential struggle in every country on earth today concerns the battle between the authority and power of permanent administration apparatus of the state – the very one that took total control in lockdowns – and the enlightenment ideal of a government that is responsible to the will of the people and the moral demand for freedom and rights.
How this struggle turns out is the essential story of our times.
CODA: I’m embedding a copy of PanCAP Adapted, as annotated by Debbie Lerman. You might need to download the whole thing to see the annotations. If you can help with research, please do.
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