Search This Blog

Monday, August 15, 2022

Plus Therapeutics: Positive Data at Conference on CNS Clinical Trials and Brain Metastases

 - Plus Therapeutics, Inc. (Nasdaq: PSTV) (the “Company”), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, yesterday presented positive data from two ongoing clinical trials of its lead investigational drug, Rhenium-186 Nanoliposome (186RNL), in the treatment of recurrent glioblastoma (GBM) and leptomeningeal metastases (LM) at the 2022 Annual Conference on CNS Clinical Trials and Brain Metastases. The conference is co-sponsored by the Society for Neuro-Oncology (SNO) and the American Society of Clinical Oncology (ASCO) and is being held August 12-13, 2022 in Toronto, Canada.

The oral presentation, titled Safety and Feasibility of Rhenium-186 Nanoliposome (186RNL) in Leptomeningeal Metastases Phase 1/2a Dose Escalation Trial [LOCL-04], demonstrated that the 186RNL dose administered through an intraventricular catheter at 6.6 mCi in 5.0 mL achieved absorbed doses of 18.7 to 29.0 Gy to the ventricles and cranial subarachnoid space, which was well tolerated with no treatment-related adverse events of greater than grade 1. Furthermore, all three patients in the cohort were observed to have prompt and complete 186RNL distribution throughout the cerebrospinal fluid (CSF) subarachnoid space that was durable past one week and very well tolerated. Importantly, all patients showed a decreased CSF cell count by microfluidic chamber assay after treatment, ranging from 65% to 92% which was also durable.

https://finance.yahoo.com/news/plus-therapeutics-presents-positive-data-170600756.html

Novartis says lung cancer drug canakinumab fails another trial

 Novartis said on Monday its canakinumab drug to help treat non-small cell lung cancer failed a phase III trial, the latest blow for the treatment which also fell short in a study last year.

The drug, used as an adjuvant treatment, did not meet its primary endpoint of disease-free survival, the Swiss company said.

Adjuvant treatments are additional cancer treatments after the primary one intended to lower the risk the cancer will return.

The failure in the latest trial, called Canopy A, is a setback for Novartis after canakinumab failed in a separate study last year where it was tried in combination with another drug and chemotherapy. "Consensus expectations for this high-risk project remained zero or low with the remaining market exclusivity for canakinumab limited until 2028," said Zuercher Kantonalbank analyst Laurent Flamme.

He estimated annual sales of around 300 million Swiss francs ($317.9 million)by 2026 for the drug as an adjuvant treatment for non-small cell lung cancer

https://www.marketscreener.com/quote/stock/NOVARTIS-AG-9364983/news/Novartis-says-lung-cancer-drug-canakinumab-fails-another-trial-41314622/

Opthea Secures up to $170 M in Non-Dilutive Financing for OPT-302 in wet AMD

 

  • Carlyle and its life sciences franchise Abingworth, working with their recently formed development company Launch Therapeutics (Launch Tx), to provide non-dilutive financing of up to US$170M, consisting of a US$120M commitment and an option to increase funding by a further US$50M
  • If OPT-302 is approved in a major market, Carlyle and Abingworth will be eligible to receive fixed success payments and variable success payments of 7% on annual net sales, which terminate after reaching four times the funded amount
  • In addition, Opthea has received commitments for US$90M1 (A$128.57M) via a private institutional equity placement for new shares and launched an A$5M Share Purchase Plan (SPP)
  • Opthea is expected to be fully funded through pivotal Phase 3 topline data and pre-commercial activities and retains full worldwide commercial rights to OPT-302
  • Financing decision driven by the potential of superior visual outcomes demonstrated in Phase 2b unlike competitors who focus on extended dosing

Sunday, August 14, 2022

Reefer madness: Cannabis in US is a ‘$100 billion opportunity,’ Tilray CEO says

 Tilray CEO Irwin Simon believes the legalization of cannabis at the federal level will provide major business opportunities in the United States.

In a recent interview with Yahoo Finance Live, Simon predicted that the opportunity would be upwards of $100 billion. 

"If you look at cannabis today in the U.S., 93% of Americans want medical cannabis legalized and about 63%, 65% want adult use," he said. "Today it’s legal in about 33 states, plus D.C. So, it’s out there that … that majority of people want cannabis [to be available] legally." 

Simon stressed that the opportunities could be extended to cannabis-adjacent products like food, personal care items, and drinks

"What will happen once the U.S. legalizes, the big companies like Diageo, Brown-Forman, ABI, even I think the Nestle's and the Unilever's will want to be into the cannabis business because they know Gen-Z, millennials, that's very much what they want," Simon said.

Simon’s comments come after Senate leaders, lead by Majority Leader Chuck Schumer, D-N.Y., last month introduced a bill that would end the federal prohibition of marijuana, allowing states to set their own laws without fear of reprisal from the federal government. 

https://www.foxbusiness.com/markets/cannabis-us-100-billion-opportunity-tilray-ceo-irwin-simon-says

Secret behind 'nic-sickness' could help break tobacco addiction

 If you remember your first hit on a cigarette, you know how sickening nicotine can be. Yet, for many people, the rewards of nicotine outweigh the negative effects of high doses.

University of California, Berkeley, researchers have now mapped out part of the brain network responsible for the negative consequences of nicotine, opening the door to interventions that could boost the aversive effects to help people quit smoking.

Though most addictive drugs at high doses can cause physiological symptoms that lead to unconsciousness or even death, nicotine is unique in making people physically ill when inhaled or ingested in large quantities. As a result, nicotine overdoses are rare, though the advent of e-cigarettes has made "nic-sick" symptoms like nausea and vomiting, dizziness, rapid heartbeat and headaches more common.

The new research, conducted in mice, suggests that this aversive network could be manipulated to treat nicotine dependence.

"Decades of research have focused on understanding how nicotine reward leads to drug addiction and what are the underlying brain circuits. In contrast, the brain circuits that mediate the aversive effects of nicotine are largely understudied," said Stephan Lammel, UC Berkeley associate professor of molecular and cell biology. "What we found is that the brain circuits that are activated after a high aversive dose are actually different from those that are activated when nicotine is delivered at a low dose. Now that we have an understanding of the different brain circuits, we think we can maybe develop a drug so that, when nicotine is taken at a low dose, these brain circuits can be coactivated to induce an acute aversive effect. This could actually be a very effective treatment for nicotine addiction in the future, which we currently do not have."

Lammel and Christine Liu, who recently obtained her Ph.D. from UC Berkeley, also found that nicotine receptors in the reward pathway become desensitized by high doses of nicotine, which probably contributes to the negative experience of high doses.

"The inhibitory inputs and the desensitization of nicotine receptors on the dopamine neurons themselves both contribute to decreased dopamine signaling in the reward pathway, then decreased feelings of pleasure and, therefore, behavioral aversion," Liu said.

Lammel, Liu, graduate student Amanda Tose and their colleagues described the brain circuits involved in nicotine aversion in a paper accepted by the journal Neuron and now posted online.

The yin and yang of dopamine

Nicotine, like cocaine and heroin, is known to cause addiction by activating the body's reward network: Nicotine binds to receptors on cells that release the neurotransmitter dopamine into the brain, where it affects everything from pain perception and mood to memory. The dopamine network, in general, provides positive feedback that reinforces our desire to seek out pleasurable activities.

But three years ago, Lammel and his colleagues discovered a parallel dopamine network that responds to unpleasurable stimuli by releasing dopamine into different areas of the brain than does the dopamine reward network. The discovery of this yin-yang nature of dopamine came at a time when it was becoming clear that dopamine performs quite different roles in various areas of the brain, exemplified by its function in voluntary movement, which is affected in Parkinson's disease.

Since then, Lammel's team has found that some chemicals also stimulate the negative dopamine network. Lammel, Liu and Tose looked closely at nicotine's effects on the body precisely because of its known aversive effects at high doses, and found that it, too, activates the network.

"This subcircuitry we reported had a major impact in the field," Lammel said. "For the first time, we identified this particular subcircuit of the dopamine system that was activated by negative emotional stimuli, such as an outburst of electrical shock. Now, we've found that a completely different stimulus -- a pharmacological stimulus, a drug -- activates the same system. This means that the system is particularly designed to be activated by aversive stimuli."

To demonstrate this for nicotine, Liu and her colleagues infused the drug into mice and measured the second-by-second release of dopamine in the brain using a recently developed technique called dLight-based fiber photometry. Previously, dopamine could only be measured over periods of minutes, which obscured the short-term responses of neurons to dopamine.

They then used chemical antagonists to inactivate a specific nicotine receptor called alpha-7 in the aversion network, which reduced the effects of aversive nicotine on neural activity. Subsequent optogenetic experiments eliminated the aversive behavior.

"In the animals where we were able to silence this population of neurons, we actually saw a strong preference for high-dose nicotine," Liu said. "So, by silencing the circuit, we were able to demonstrate for certain that this was a very important neural encoder of the behavioral aspect of high-dose nicotine."

The only drug designed to help with nicotine cessation, varenicline, could work by increasing aversion via the alpha-7 receptor and lessening desensitization of the alpha-4/beta-2 receptor, she said, but its precise mechanism of action is currently unknown.

Lammel noted that drugs that block the alpha-7 nicotinic acetylcholine receptor might not work as a treatment for tobacco or nicotine addiction because they would block many necessary functions of the receptor. But identifying this nicotine receptor as key to mammals' aversion to high-dose nicotine will help researchers develop targeted drugs to tweak the body's response to a typical dose that a smoker would ingest when lighting up a cigarette.

"Maybe in the future that will be an approach for nicotine addiction therapy, where we use genetic editing technologies to selectively target these receptors in specific brain circuits and then overexpress or delete receptors," Lammel said. "What we deliver here is a blueprint of a brain circuit and nicotine receptor subtype that is critically important for nicotine's aversive properties."

The work was supported by the National Institutes of Health (1R01DA042889), California's Tobacco-Related Disease Research Program (26IP-0035), the One Mind Foundation (047483), the Brain Research Foundation (BRFSG-2015-7) and the Wayne and Gladys Valley Foundation. Liu, now a postdoctoral fellow at UC San Francisco, was a Howard Hughes Medical Institute Gilliam Fellow and an NSF Graduate Research Fellowships Program (GRFP) fellow. Tose was an NSF GRFP fellow.

Other paper co-authors are Jeroen Verharen, Yichen Zhu, Lilly Tang, Johannes de Jong and Jessica Du of UC Berkeley and Kevin Beier of UC Irvine. All Berkeley researchers are members of the campus's Helen Wills Neuroscience Institute.


Story Source:

Materials provided by University of California - Berkeley. Original written by Robert Sanders. Note: Content may be edited for style and length.


Journal Reference:

  1. Christine Liu, Amanda J. Tose, Jeroen P.H. Verharen, Yichen Zhu, Lilly W. Tang, Johannes W. de Jong, Jessica X. Du, Kevin T. Beier, Stephan Lammel. An inhibitory brainstem input to dopamine neurons encodes nicotine aversionNeuron, 2022; DOI: 10.1016/j.neuron.2022.07.003

Rapid, at-home prototype saliva test that's as good as RT-PCR

 At-home COVID-19 tests have become an easy way to self-diagnose. But current tests have drawbacks, such as the length of time it takes to get an answer, or how accurately the test can identify a positive case. And most of them require the uncomfortable procedure of sticking a swab up one's nose. Now, researchers reporting in ACS Sensors have developed a SARS-CoV-2 saliva assay and prototype device that combine speed and ease with high sensitivity.

The two main options for at-home COVID-19 testing today are rapid antigen tests and those based on reverse transcription polymerase chain reaction (RT-PCR). Rapid antigen testing delivers a result directly to the user in about 15 minutes, but it's not very sensitive and can provide a false-negative signal, meaning someone could unknowingly infect others. Though RT-PCR is known as the "gold-standard" assay because of its high sensitivity and specificity for SARS-CoV-2, it requires the sample to be sent away to a lab and be analyzed by specialized personnel. The analysis itself can take up to an hour, but the total time from swab to answer can take days. Plus, both methods require the uncomfortable process of swabbing the back of your nose.

Non-invasive saliva-based tests exist, but they also rely on the slow and specialized RT-PCR approach. A similar method called reverse transcription loop-mediated isothermal amplification (RT-LAMP) can also detect viral SARS-CoV-2 RNA at a level of specificity and sensitivity consistent with RT-PCR, but it's quicker, cheaper and easier to use. Therefore, Weihua Guan and colleagues wanted to see if they could use RT-LAMP to create a fast and sensitive COVID-19 test that only requires a saliva sample; a palm-sized, portable device; and a smartphone.

The researchers integrated several steps into one compact machine, which they call the saliva-based SARS-CoV-2 self-testing with RT-LAMP in a mobile device (SLIDE). Its five distinct modules conduct all of the steps needed for RT-LAMP: heating the sample, mixing it with RT-LAMP reagents, carrying out the reaction, detecting how much viral RNA is present and communicating that result to a smartphone. To use SLIDE, a person simply spits into a vial on a cartridge that they insert into the device, and results are sent to a smartphone within 45 minutes. In lab tests, SLIDE successfully detected and quantitated a mock saliva sample spiked with inactivated SARS-CoV-2 virus particles, as well as a real saliva sample from someone known to be positive for COVID-19. In both cases, the results were consistent with those from RT-PCR, which suggests that the SLIDE device could be a quick, easy and sensitive way to tell whether someone has COVID-19, say the researchers.

The authors acknowledge funding from the National Institutes of Health, National Science Foundation and Penn State Coronavirus Research Seed Fund.


Story Source:

Materials provided by American Chemical SocietyNote: Content may be edited for style and length.


Journal Reference:

  1. Zifan Tang, Jiarui Cui, Aneesh Kshirsagar, Tianyi Liu, Michele Yon, Suresh V. Kuchipudi, Weihua Guan. SLIDE: Saliva-Based SARS-CoV-2 Self-Testing with RT-LAMP in a Mobile DeviceACS Sensors, 2022; DOI: 10.1021/acssensors.2c01023

No ‘slam dunk fix’ in HIPAA privacy law to protect abortion patients

 Abortion advocates and Democratic lawmakers are calling on the Biden administration to protect data on patients seeking abortion services, as concerns mount that clinic and hospital information could be used to prosecute individuals who seek the procedure in states where it’s illegal.

Possible actions involve the Health Insurance Portability and Accountability Act, an oft-cited yet little-understood law that protects sensitive medical information from being disclosed without a patient’s consent or knowledge.

But HIPAA doesn’t provide the sweeping health data protections that many Americans think it does. And there’s little federal agencies can do to strengthen the law without help from Congress, according to multiple data privacy and legal experts interviewed by Healthcare Dive. 

Any actions the HHS takes to make HIPAA stricter or prevent abortion-related data from being shared with law enforcement are likely either unenforceable, subject to legal challenges or will take too long to help patients in the near-term, experts said.

In this legal environment, providers — torn between concerns of legal retribution and their duty to patients — should focus on minimizing and protecting the data they collect, while keeping abreast of shifting abortion legality in their state.

“Typically the laws are trying to catch up with where the real world is, in terms of what’s going on. This time we have the inverse of that situation, where the real world is trying to catch up or adjust or modify to the law,” said Bruce Armon, a health law attorney at Saul Ewing Arnstein & Lehr. “The best thing for the provider community is to pay attention to developments almost on a daily basis.”

HIPAA’s law enforcement exception

Following the Supreme Court’s landmark decision to overturn Roe v. Wade in June, dozens of states swiftly restricted access to abortion care. The ruling kickstarted a national conversation about privacy, as digital records like text messages, browser histories and emails have been used to prosecute pregnancy-related criminal charges in the past.

Medical data stored by healthcare providers could also be leveraged to prosecute patients and providers, despite being under HIPAA’s privacy umbrella.

”There’s many gray areas, gaps in it,” said Ashley Thomas, senior counsel at Holland & Knight.

Under HIPAA, law enforcement is allowed to request patient information from covered entities, and covered entities are permitted, but not required, to comply.

According to recent guidance published by the HHS, if a state law prohibits abortion but doesn’t expressly require providers to report it, a provider that reports instances of the procedure is violating HIPAA.

But providers are allowed to report abortion data if they receive a court order or summons. Those could become more frequent as conservative state attorneys general crack down on reproductive healthcare.

“There’s a lot of things that are gray here and they’re overlapping and intersecting and changing very fast,” said Matthew Bernstein, founder of information management consultancy Bernstein Data.

    Providers looking to protect their patients from prosecution could decide not to respond to law enforcement requests as a policy, unless they come in the form of a warrant, said Lucia Savage, chief privacy and regulatory officer at Omada Health.

    But subpoenas or court orders aren’t something providers can ignore without opening themselves up to a lawsuit, though complicated legal nuances could arise for providers performing abortions on out-of-state patients. Absent federal protection for the procedure, some conservative states, including Missouri, are eyeing ways to prosecute out-of-state providers if they perform abortions on patients from their state of residence.

    “It sounds unconstitutional. But a lot of this sounds unconstitutional to me,” said Dianne Bourque, a partner at Mintz specializing in healthcare law.

    No ‘nice clean slam dunk fix’

    President Joe Biden signed an executive order in July calling on Federal Trade Commission Chair Lina Khan and HHS Secretary Xavier Becerra to consider issuing new HIPAA guidance to protect against digital surveillance.

    Some Democratic senators have urged HHS to go further and update the law to limit or explicitly prevent health data from being shared with law enforcement agencies targeting people who have an abortion.

    The HHS Office of Civil Rights, which oversees HIPAA, is “going to look at all its options. That’s what an agency does in response to an executive order. But I think its options are going to be limited,” said Savage, who was chief privacy officer of HHS’ health IT arm during the Obama administration.

    Regulators could have some authority here. The HIPAA statute is bare-bones, and the bulk of how it’s interpreted today comes from rules and regulations. The OCR could issue nonbinding subregulatory guidance, attempt rulemaking or increase enforcement actions, experts said.

    To fully close or mitigate the law enforcement exception with respect to abortion, regulators would have to issue new rules. That takes time — sometimes, years pass between when a rule is proposed and when it’s finalized — and wouldn’t help patients or providers in the interim.

    “The regulatory process can take years. We have providers who have literally days, maybe a week or two, to determine how to appropriately care for a patient,” Armon said.

    The OCR could also try to cram abortion data protections into a notice of proposed rulemaking on new HIPAA rules from 2021. Regulatory agencies have flexibility between the content of a notice and the content of a final rule, as long as the final rule meets the standard of a logical outgrowth from the original, Savage said.

    Among other things, the 2021 NPRM attempts to increase permissible disclosures of personal health information and improve care coordination and case management. Regulators could try to find grounds to argue protecting reproductive health data slots represents a natural outgrowth from that NPRM, Savage said.

    The OCR also need to watch out for the parameters for drafting HIPAA regulations, lawyers said. Any change to HIPAA regulations would have to align exactly with the statute to ensure the Biden administration doesn’t overstep in terms of overruling state law.

    A section of HIPAA says that nothing in the law can be construed to invalidate or limit the authority or power of a state law in specific circumstances, including providing for the reporting of disease or injury, death or public health intervention.

    Conservative states could use these circumstances to sidestep any HHS effort to increase HIPAA protections for abortion patients, Mintz’s Bourque said. For example, if a state attorney general positions a request for abortion data as related to preventing injury, but the OCR has restricted providers’ ability to share that data, the state could say HHS has exceeded the boundaries of what HIPAA allows it to do, likely launching a legal fight.

    “It’s impossible to say yes this will work, no this won’t work. But this is the ground for arguing about it,” Bourque said. “There’s not a nice clean slam dunk fix.”

    That’s one of many legal twilight zones emerging in the ongoing fight over abortion access, as complications crop up for both pro-choice and anti-abortion factions in federal and state governments.

    For example, even if the HHS explicitly says providers can’t share abortion-related data with law enforcement agencies, a public health agency could query and receive that data from providers by framing it as a public health request, and share it with law enforcement, Bourque said.

    In addition, providers under HIPAA are allowed to disclose PHI that they think is evidence of a crime that occurred on the premises. In a state where abortion is criminalized, if a healthcare worker believes an illegal abortion has occurred, they are allowed to share that information with authorities without a patient’s permission.

    If the HHS moves to restrict abortion data sharing, HIPAA could become contradictory with itself, lawyers said. It could also run afoul of whistleblower protection laws, if medical workers who report abortions are protected in good faith reporting a violation of law.

    “I don’t know who wins that,” Bourque said. “It’s this perfect storm.”

    Provider best practices

    The best solution would be for Congress to act to address gaps in HIPAA and U.S. privacy laws to resolve concerns related to reproductive rights, experts said. But in the absence of comprehensive action, it’s largely falling to providers to protect patient’s medical data — and themselves from legal retribution, especially if they operate in a state where abortion is illegal.

    Providers should collect the bare minimum of data they need to provide patient care and be very cognizant of retention obligations, especially for data that could reveal what reproductive health services patients have received, experts suggested.

    “If you don’t need to collect it, don’t collect it. And if you no longer need to retain it, dispose of it,” Bernstein said.

    Physicians aren’t necessarily required by law to include in the record that a patient showed signs they might have had an abortion. That could mitigate the fallout if they receive an enforceable subpoena from law enforcement, Thomas said.

    It’s also important to be knowledgeable about what you can and cannot do under HIPAA, Bourque said.

    The lawyer said she’s seen instances where state forms require a lot more to be shared by the provider than what the statute actually authorizes.

    “It’s really important that everybody proceeds with caution,” especially in the face of potential overreaching by enforcement authorities, Bourque said. “To comply with HIPAA you have to comply with the bare minimum. Provide what’s asked and not more, otherwise you’ve got a HIPAA problem.”

    https://www.healthcaredive.com/news/hipaa-privacy-law-abortion/627319/