How Does Elysium Therapeutics’ Hydrocodone Prodrug, O2P, Work?
Could you tell our audience a bit about O2P and its development journey?
Greg Sturmer: When you look at the key features of O2P, and we talked about these inherent risks of existing opioids, I think you could probably put them into four different buckets. One of the inherent risks of existing opioids relates to oral abuse, and fatal overdose. Another is non-oral abuse and fatal overdose. A third diversion: giving your pills to someone else, or someone else getting a hold of your pills, and addiction. Let’s just briefly talk about those. Oral abuse and fatal overdose; what O2P does, we reduce the exposure to the opioid, in this case, hydrocodone when more than recommended doses are ingested. So this reduces the risk of abuse and fatal overdose. And we actually demonstrated this in our human proof of concept study that we recently completed. O2P also provides, and this quite frankly, we exceeded our expectations. When we did our human study, O2P actually provides a longer duration of action than existing opioids. That means that when a prescription is given for an O2P hydrocodone, it will take fewer tablets, significantly fewer tablets, and what fewer tablets means, coupled with our oral overdose protection, is we’re further reducing the risk of opioid abuse, diversion, and fatal overdose. Just to put this in perspective, there’s been a lot of effort of late to restrict the number of days that a doctor can prescribe. So even in that context, say that a doctor is only allowed to give eight days’ worth of pain relief, there would be no potential for lethal overdose with O2P. Even if someone took the entire bottle on day one when they received it. And that compares to existing opioids where there would be eight potential lethal overdoses. So that’s kind of the stark contrast that our technology is bringing forward.
Next, in the non-oral route of abuse and fatal overdose, I already touched upon this, so I don’t mean to talk about it much further, but our technology relies on this natural digestive process, so injecting or inhaling is not going to release hydrocodone. What we’ve also done, though, is made it really difficult to tamper with. We sent our drug, actually, to an independent lab, and said, “Beat it up, see if you can get the hydrocodone out of it.” And the results showed how robust our technology is. The third issue of diversion, I think I may have mentioned this before, over 70% of abusers, they obtained the prescription opioids that they abused from friends or family, so they’re not getting prescribed directly. They may have at the beginning, but now they’re relying on getting it from other sources. Well, O2P reduces the risk of diversion by significantly reducing the number of pills that will be prescribed. And then finally, when you talk about risks of addiction or abuse that might lead to addiction. Each prescription will have far fewer potential euphoric episodes. An abuser, what they’re looking for is, “I want to get high. I want to feel these euphoric effects as fast as I can, as long as I can, and as many times as I can.” And unfortunately that “as many times as you can,” that’s that reinforcement of behavior that can lead to addiction. So with O2P opioids, we can dramatically reduce the number of euphoric episodes that would reinforce that type of behavior.
Finally, the cool thing about our technology is it’s applicable to all oral opioids. So we’re first applying it to hydrocodone because it’s the most prescribed opioid, but next could be oxycodone, morphine, oxymorphone, hydromorphone, and then also O2P opioids that are used for opioid use disorder like buprenorphine and methadone. So a lot to be done within the opioid space, and much could be done outside of the opioid space as well with our technology.
Spotify scrambling to remove dozens of podcasts promoting online prescription drug sales
NEW YORK — If you search “Adderall” on Spotify’s podcast page, you’ll find health podcasts about ADHD, shows about addiction recovery and comedy podcasts where hosts talk about using the medication. You may also come across multiple pages masquerading as podcasts that direct users to buy drugs from potentially dangerous and illegal online pharmacies.
The intention of many of these pages is obvious from their names. Podcasts with titles, such as “My Adderall Store” – which has a link in the episode description to a site that purportedly sells Adderall, as well as potentially addictive pain medications like Oxycodone and Vicodin, among other drugs – were listed within the first 50 suggested results, a CNN review this week found.
CNN identified dozens of these fake podcasts across Spotify, advertising sales of medications ranging from Methadone to Ambien, in some cases claiming that the drugs can be purchased without a prescription, which is illegal in the United States.
Spotify is now scrambling to remove these fake podcast pages, which violate its rules and which, at best, may be spam and, and worst, could direct users to sites that violate the law.
Within hours after CNN sent Spotify a list of 26 podcasts promoting online pharmacies that were live as of Thursday afternoon, the platform had removed them. A spokesperson said they violated its rules, which prohibit illegal and spam content. Still, even after Spotify removed the podcasts CNN sent on Thursday, others continued to appear on the platform Friday morning.
“We are constantly working to detect and remove violating content across our service,” a Spotify spokesperson told CNN in a statement.
The findings come as parents have urged tech giants to crack down on the sale of counterfeit or illicit drugs to young people through their platforms, after multiple teens have died of overdoses from pills bought online. They also raise questions about Spotify’s moderation capabilities as AI makes it easier than ever to churn out fake content.
Lauren Balik, who runs a blog about tech company stocks, called on Spotify CEO Daniel Ek to address the fake podcast issue in a post on X earlier this week. Business Insider also published a report on the issue on Thursday that said it flagged hundreds of the podcasts that Spotify subsequently removed.
Multiple US government agencies have warned that ordering medications from online pharmacies may be illegal and could have harmful – and potentially deadly – consequences.
In 2011, Google was fined $500 million for running ads for Canadian online pharmacies illegally selling prescription drugs to US consumers, after which the internet giant took various steps to combat online pharmacies appearing in ads or search results. And in 2018, the US Food and Drug Administration called on tech platforms, including Facebook, Reddit and Twitter (now called X), to do more to prevent illegal opioid sales on their sites.
Still, tech platforms that host content pointing users to those sites, are largely subject to “a lack of any repercussions, any accountability,” according to Katie Paul, director of the non-profit Tech Transparency Project. That’s because federal law generally protects tech platforms from liability over what users post on their sites.
“There’s no regulations,” Paul added.
Podcasts advertise ‘delivery without prescription’
Even after the issue was called to Spotify’s attention, CNN was easily able to find dozens of these fake, drug sales podcast pages, including some that had been posted on the platform for months.
One such podcast, called “Xtrapharma.com,” posted eight episodes, each less than 10-seconds long, on November 29, 2024. The episodes featured a computerized voice advertising Xanax, Percocet, Oxycontin or Hydrocodone for sale “with FDA-approved delivery without prescription.”
“Our platform provides a seamless experience for those seeking solid medications like Xanax,” the Xtrapharma.com podcast description on Spotify read. “With just a few clicks, you can avail yourself of this trusted medication from the comfort of your home, ensuring discretion and convenience while prioritizing your mental health needs.”
Another podcast titled “Order Xanax 2 mg Online Big Deal On Christmas Season” posted its only episode on December 2 last year. In the 26-second episode, a computerized voice said, “Are you a health-conscious guy? Presenting the best health advisor episode first time on Spotify,” before describing Xanax. Its description linked users to an online pharmacy that claims to deliver “Government approved medicine to the customer’s doorstep.”
The proliferation of text-to-speech tools has made it easier and faster to create large volumes of this kind of spammy content.
“I think podcasts have a bigger blind spot, because … voice makes it much more difficult for moderation,” Paul told CNN.
One Spotify podcast titled “John Elizabeth,” with thumbnail art advertising a pharmacy website, had dozens of episodes featuring a voice that sounds computer-generated. The website advertised was the same as that promoted on another podcast, called My Adderall Store.
“If you’re in search of Ativan for sale online with fast delivery, you’re in luck,” the voice said in one episode of the show. “Our online store offers a hassle-free shopping experience, making it easy for you to get the medication you need without any trouble.”
On an initial CNN search of Spotify podcasts for “Adderall,” at least seven podcasts advertising online pharmacies showed up within the first 100 results. On a search for “Xanax,” 20 of the first 60 results promoted online pharmacies. And on a search for “Valium,” two of the first five suggested results were promoting online pharmacies.
Fake podcasts also surfaced in searches for “Vyvanse,” “Codeine” and “Percocet,” such as a show titled “How Percocet Dosage Taken No RX” with episodes like “Order Codeine Online Safe Pharmacy Louisiana” that linked to an online pharmacy along with a coupon code.
None of the drug sales podcasts that CNN viewed had been rated by users on the platform, so it’s not clear how many people may have viewed or interacted with them. CNN could not confirm if orders placed through these sites would actually be delivered.
Spotify’s moderation rules
In some cases, after CNN engaged with these podcasts – including one called “Adderall 10 mg blue pills” – the site appeared to remove them; links to the shows redirected to a page saying, “Sorry, that’s not currently available.” However, more than two dozen others remained active until CNN asked Spotify about them.
Spotify offers free tools that allow anyone to create, distribute and, potentially, monetize podcasts. However, it notes in its creator guidelines that its mission to “democratize audio” doesn’t mean “anything goes on our platform.” Those guidelines prohibit, for example, hateful content, sexually explicit content, illegal content and spam, including content made “solely to … promote a product or service.” The platform says it may remove content that violates those creator guidelines.
“Mass publishing identical or indistinguishable content that directs listeners to potentially harmful sites or services, or violates our monetization policies,” Spotify said in the guidelines.
Separately, Spotify’s platform rules also prohibit “content that illicitly promotes the sale of regulated or illegal goods,” including illegal drugs. It says it uses both automated technology and human reviewers to enforce its rules.
Spotify has previously been criticized over health-related content on the platform.
In 2022, several prominent artists raised concerns or pulled their music catalogues from the site, in protest of its popular podcast “The Joe Rogan Experience,” which had repeatedly spread false claims about vaccines and the pandemic. In response, Spotify added a content advisory to all podcast episodes that discuss Covid, directing users to trusted sources. (Rogan also promised to do more thorough research and provide more balanced information about Covid.)
The company continued to ramp up its moderation efforts following that 2022 debacle, including establishing a Safety Advisory Council to provide feedback on Spotify’s rules and enforcement. It also acquired Kinzen, a machine learning startup capable of screening audio content for rules violations.
But online safety experts say the fake podcasts are a sign that Spotify needs to do more to protect its platform.
“What’s true is that anywhere people can post user-generated content, you will find … people selling drugs,” said Sarah Gardner, CEO of the Heat Initiative, a non-profit that advocates for child safety online. “That part is, unfortunately, pretty consistent. It’s really about what the companies do to combat it.”
Hydrocodone Rescheduling Fueled Online Drug Sales
Hydrocodone was once the most widely prescribed and one of the most abused drugs in the United States. Over 135 million prescriptions were filled in 2012 for hydrocodone combination products such as Vicodin, Lortab and Norco.
Then in 2014 the Drug Enforcement Administration rescheduled the opioid painkiller from a Schedule III controlled substance to the more restrictive category of Schedule II. The move was intended to reduce the prescribing of hydrocodone – and it quickly had the desired effect. By 2017, only 81 million prescriptions for hydrocodone were filled.
But while legal prescriptions for hydrocodone have gone down, the DEA’s 2014 rescheduling may have fueled a surge in illegal online sales of hydrocodone and other opioids, according to a new study in the British Medical Journal.
“The scheduling change in hydrocodone combination products coincided with a statistically significant, sustained increase in illicit trading of opioids through online US cryptomarkets. These changes were not observed for other drug groups or in other countries,” wrote lead author Jack Cunliffe, PhD, a lecturer in data analysis and criminology at the University of Kent.
Cunliffe and his colleagues studied these online cryptomarkets – also known as the “dark web” – by using web crawling software that scans the internet looking for websites dedicated to online sales of illicit drugs. From October 2013 to July 2016, they found that sales of prescription opioids on the dark web nearly doubled, from 6.7% to 13.7% of all online drug sales.
“Our results are consistent with the possibility that the schedule change might have directly contributed to the changes we observed in the supply of illicit opioids,” said Cunliffe. “One explanation is that cryptomarket vendors perceived an increase in demand and responded by placing more listings for prescription opioids and thereby increasing supply.”
Iron Law of Prohibition
The increase in supply and demand wasn’t just for hydrocodone. The researchers also noted a growing number of online listings for more potent opioids, such as oxycodone and fentanyl. They attribute that to the “iron law of prohibition” – banning or reducing the supply of one drug encourages users to seek more potent drugs from new sources.
“We found that users were first buying oxycodone followed by fentanyl. Drug users adapt to their changing environment and are able to source drugs from new distribution channels if needed, even if that means by illegal means. In a context of high demand, supply side interventions are therefore likely to push opioid users towards illicit supplies, which may increase the harms associated with their drug use and make monitoring more difficult,” Cunliffe wrote.
As PNN has reported, business is booming for illegal online pharmacies. As many as 35,000 are in operation worldwide and about 20 new ones are launched every day. About half are selling counterfeit painkillers and other medications. Overdoses involving fentanyl and other synthetic opioids – most of them purchased on the black market – have also increased and now outnumber those linked to prescription opioids.
“The study’s findings are troubling but not surprising. As you’ve well reported, there are often unexpected and negative externalities resulting from well-intended anti-addiction interventions,” Libby Baney, Principal, Faegre Baker Daniels Consulting and senior advisor to Alliance for Safe Online Pharmacies said in an email to PNN.
“What’s worse still, when buying medicine online – whether from dark or surface web sellers – it is virtually impossible for the consumer to know if the product is what it claims (in this case, an opioid like oxycodone) or is a dangerous counterfeit laced with a deadly dose of elephant tranquilizer or poison. As too many victims have shown, even one pill can kill.”
A recent study at the University of Texas Medical Branch also found an association between hydrocodone’s rescheduling and increased opioid abuse. Researchers found that hydrocodone prescriptions for Medicare patients declined after rescheduling, but opioid-related hospitalizations increased significantly for elderly patients who did not have a prescription for opioids
