Biden takes victory lap on insulin cap, after rescinding Trump cap

 President Joe Biden jumped on social media Saturday night to take a victory lap on the Inflation Reduction Act, a signature piece of legislation the president is parading ahead of November’s midterm elections.

In a pair of tweets, Biden — who campaigned on "Bringing America together" and "uniting our nation" — knocked Republicans for supporting only "the wealthiest Americans" and opposing a cap on insulin prices.

"If you’re on Medicare, your insulin will be capped at $35 a month thanks to the Inflation Reduction Act. We wanted to cut the cost of insulin for everyone—including hundreds of thousands of children with Type 1 diabetes—but Republicans voted to strike that out of the bill," Biden tweeted.

In a separate tweet, Biden claimed Republicans were swift to help corporations. Democrats, he said, were swift to implement taxes against them.

"Republicans had no problem enacting a $2 trillion tax cut that overwhelmingly benefited the wealthiest Americans and biggest corporations," the president tweeted. "Now, thanks to the Inflation Reduction Act, corporations will have to pay a minimum corporate tax of 15%."

Biden’s $430 billion Inflation Reduction Act, which he signed into law in August, caps the cost of a month’s supply of insulin to $35. Medicare recipients will also not have to pay a deductible for insulin, starting on January 1, 2023.

The law also authorizes the federal government to negotiate prices on some prescription drugs and cap costs for the government's Medicare health program, Reuters reported.

The government will start negotiating prices for 10 drugs in 2024, which are slated to take effect in 2026. The first of the medicine prices to be negotiated will be for medications that treat diseases such as diabetes, cancer and arthritis. The specific medications will be announced in 2023.

The new law also caps out-of-pocket pharmacy drug costs for those enrolled in Medicare at $2,000 per year, starting in 2025.

While Biden’s victory lap included criticizing Republicans for not supporting the cap, it was Republicans — namely former President Donald Trump in 2020 — that first limited the cost of Part D prescription insulin to a maximum $35 copay for a month’s supply.

"President Trump has forged partnerships with pharmaceutical manufacturers and plans to deliver lower priced insulin to our nation’s seniors," Centers for Medicare & Medicaid Services (CMS) Administrator Seema Verma said at the time. "This market-based solution, in which insulin manufacturers and Part D sponsors compete to provide lower costs and higher quality for patients, will allow seniors to choose a Part D plan that covers their insulin at an average 66 percent lower out-of-pocket cost throughout the year."

Biden rescinded the Trump healthcare action within his first year in office.

video

Trump announces insulin price cap for senior citizens

Trump touts massive cuts in insulin prices for affected Americans

In recent weeks, Biden has increased his propagandizing against Republicans as the midterm elections are just over 30 days away.

His recent tweets from the official presidential account include calling some Republicans "extremist," suggesting Trump supporters are "pro-insurrection," claiming the Republican Party would enact a nationwide abortion ban and that the GOP would "enact extreme policies to threaten access to basic health care."

https://www.foxbusiness.com/markets/biden-takes-victory-lap-inflation-reduction-acts-insulin-cap-blames-republicans

You Didn’t Invent That Drug

 Remember when Barack Obama declared that companies owe their success to the government? “You didn’t build that,” he said. Well, now the National Institutes of Health claims credit for Biogen‘s

A new treatment for Alzheimer’s disease showed success in a large trial last week.

“Potentially promising outcomes such as this one are the result of continued public investment in medical research, the tireless work of scientists around the world, and assistance for people with Alzheimer’s disease and their caregivers,” the National Institutes of Health wrote in a news release this week. Although the National Institutes of Health did not fund the successful study, it says that “decades of research paved the way” for it.

Sorry. The apparent success of Biogen is mainly due to the sustained private investment in drug research and development over many decades, which has led to dozens of failures and write-offs of billions of dollars in investments. Biogen may finally recoup some of its investment with a new Alzheimer’s drug, if the Biden administration allows it.

Amyloid buildup is associated with Alzheimer’s disease. Many scientists believe that removing amyloid from the brain can slow cognitive decline. But the long line of failed amyloid therapies has raised doubts in some quarters. Many rejected the first-in-class amyloid drug Aduhelm from Biogen despite positive results from a late-stage trial because another trial showed mixed results.

The Food and Drug Administration approved Aduhelm based on the entirety of the evidence. But Medicare refused to pay for it and other anti-amyloid treatments that might get rapid government approval outside of clinical trials because they weren’t convinced that removing amyloid could slow the disease. Biogen’s new experimental drug lekanimab provides more evidence that it can.

Even the National Institutes of Health seem to agree. Lecanemab slowed the rate of cognitive decline by 27% over 18 months, similar to Aduhelm. “Government funding has been integral to helping us understand the role of amyloid, the protein targeted by lekanimab,” says the National Institutes of Health. Well, but Biogen and other drug makers have taken the risk of investing complications of that in experimental treatments without guaranteeing they will ever pay off.

The failed experiments led Biogen to specifically scan patients’ brains for amyloid. However, the National Institutes of Health is trying to claim credit for this revelation, writing that “selection of participants in lecanemab clinical trials is based on amyloid positron emission tomography, a technology developed with publicly funded research.”

Government bureaucracies like to take credit, but the National Institutes of Health essentially claims the intellectual property for Biogen. Will the NIH also claim inventors’ rights to Biogen’s patents so it can earn royalties on its drug sales, as it did with Moderna on its Covid-19 vaccines because its scientists contributed to coronavirus vaccine research?

Progressives also say that the Bayh-Dole Act allows the federal government to seize patents for drugs developed with government funding. You can expect to hear this argument if Medicare covers lecanemab. The administration’s political narrative is that drug makers are greedy and don’t care about patients.

It’s possible that the agency is just trying to get Congress to give it more money, but the government never stops absorbing all it can. Sorry, NIH, you didn’t invent that.

https://chof360.com/you-didnt-invent-that-drug/

Congressman Escalates War With PBMs

 Representative Buddy Carter, BSPharm (R-Ga.), a pharmacist and former pharmacy owner, on Friday escalated his longstanding battle against pharmacy benefit managers (PBMs), releasing a report critical of the industry and calling for changes in the PBM rebate system.

"What we're trying to achieve in healthcare is accessibility, affordability, and quality," Carter said at a press conference in the parking lot of a pharmacy here. "PBMs are hurting accessibility, affordability, and the quality of healthcare."

Carter issued a report entitled "Pulling Back the Curtain on PBMs: A Path Towards Affordable Prescription Drugs." The report included stories from patients who had experienced difficulties in accessing their medications due to PBM rules or excessively high drug costs.

The report also urged support for a regulation issued by the Trump administration -- but delayed by the Biden administration -- that would force drug company rebates to be passed along to patients at the point of sale, rather than being absorbed by the PBMs. And it urged support for legislation now in Congress, such as the Pharmacy DIR Reform to Reduce Senior Drug Costs Act and the Drug Price Transparency in Medicaid Act, that would curb some PBM authorities and force them to be more transparent about their pricing strategies.

At the press conference, speakers -- several of whom also appear in Carter's report -- outlined the issues they were having receiving their medications. Jessica Wofford, a nurse who has had Crohn's disease for 15 years, said that her monthly 1-ml injection of ustekinumab (Stelara) is $24,900. "My insurance company is wonderful in that they will pay $17,000 of this, leaving the rest of the $7,000 to me to figure out how I'm going to pay for it."

Wofford said she is enrolled in two copay assistance programs to help make up the difference. "I'm enrolled in the second one because I maxed out of the first one in March of this year ... And the problem with these kinds of medications is that they're authorized by your insurance, [but] your insurance will only authorize this through one particular specialty pharmacy. You cannot shop these medications; you cannot go online, unfortunately, and find better prices."

Terry Wilcox, CEO and founder of Patients Rising NOW, a group of patients advocating for better access to treatment, said that she recently went to a pharmacy to pick up ear drops for her son. "They said, 'That'll be $210.'" When Wilcox said the price wasn't usually that high and that the GoodRx app quoted a price of $80, the pharmacy told her she couldn't pay that price because it wouldn't count toward her deductible.

"I was like, 'Why would I want to pay two and a half times more for something just so that it can count towards my deductible? I want this,'" she said. "So I ended up paying that price. But that's the shenanigans you go through."

Elisa Comer, a healthcare administrator, said "there should never be a case where a pharmacist or physician has to tell a mother she can't [access] medication for a child with juvenile arthritis," sending the child back into a wheelchair for the next year and a half. "These are true stories," said Comer. She said that she herself fought so hard with PBMs one year that "I had to give up and go off my medication."

"I have a message for you PBMs out there: we're on to you and we're coming for you," she said. "These are hills that we are willing to die on. And we're tired of you hijacking our healthcare. And a word for my chronic illness family -- you stay the course, you stay in there and fight. 'Let's roll.'" Her last remark a quote from Todd Beamer, a passenger on one of the hijacked September 11, 2001 flights, who said "Let's roll" before he and some fellow passengers stormed the pilots' cabin in an effort to derail the hijackers.

Asked for their response, the Pharmaceutical Care Management Association, a trade group for PBMs, sent a statement saying that "Americans consistently reject the use of blame game tactics, especially when real patients' health and lives are at stake. This is especially true when it comes to blaming PBMs, the one entity reducing costs in the healthcare system."

"An overlooked reality is that, for the majority of Americans, average patient out-of-pocket costs are actually decreasing thanks to PBM's [sic] proven ability to negotiate discounts from pharmacies and drug manufacturers on behalf of patients," the statement said. "Without the affordability and care coordination provided by PBMs, patients' access to their medications will be limited. We urge other members of the prescription drug supply and payment chain to put down their swords, and join us in making prescription drugs more affordable for more Americans."

https://www.medpagetoday.com/pharmacy/pharmacy/101124

NYC shoplifter with 153 arrests booked again after fleecing three Rite Aids

 

A prolific Big Apple shoplifter with over 150 arrests dating back to his teens was busted again in Queens this week, sources told The Post.

Tedera Williams, 47, was nabbed on Friday for three separate incidents in which he stole beer from three separate Rite Aids in Queens.

The thefts included seven cases of Corona beer and a shopping cart on Sept. 21, stolen Heineken on Sept. 23 and another 12-pack of Coronas on Friday.

He is separately facing petit larceny charges from a string of Sept. 8 incidents, according to public records. He was arrested in Manhattan on several misdemeanor larceny charges on Sept. 25 after being caught stealing a polo shirt, belt and jeans from Bloomingdale’s on the Upper East Side, and released without bail.

Williams was first arrested as a teen, but the early busts are sealed, sources said.

ADVERTISEMENT

His publicly available rap sheet begins Jan. 10, 2000, and includes at least 153 arrests including for charges of petit larceny, robberies, tampering with evidence, stealing, burglary and forcible touching in 2019 for rubbing a 22-year-old woman’s butt.

He remained in custody as of Saturday evening.

https://nypost.com/2022/10/08/nyc-shoplifter-with-153-arrests-booked-again-after-fleecing-three-rite-aids/

Oncorus Publishes on Synthetic vRNA/LNP Platform for the Treatment of Cancer

 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapies company focused on stimulating the immune system to transform outcomes for cancer patients, today announced the publication of preclinical data in Nature Communications highlighting the potential of its synthetic viral RNA (vRNA)/lipid nanoparticle (LNP) platform as a novel approach to treating cancer by enabling repeat intravenous (IV) administration of viral immunotherapy. Data published today demonstrate vRNA/LNP delivery and selective replication, virus assembly, spread and lysis of tumor cells, leading to potent anti-tumor efficacy even in the presence of virus neutralizing antibodies in the bloodstream.

The article describes the design and development of Oncorus’ synthetic RNA viruses for the systemic treatment of cancer. The IV delivery of viral RNA genomes for two picornaviruses, Seneca Valley Virus (SVV) and Coxsackievirus A21 (CVA21), was formulated in LNPs. By encapsulating vRNA in LNPs, Oncorus was able to recapitulate oncolytic viral therapy in various tumor cells and avoid neutralizing antibodies. The vRNA/LNP constructs were well tolerated and elicited tumor-specific in situ production of oncolytic virions, immune cell recruitment and tumor destruction. Efficacy was observed across multiple cancer models, including xenografts, PDX, GEMM and syngeneic models, with survival benefit observed in an orthotopic small cell lung cancer (SCLC) tumor model. Overall, synthetic RNA viruses were well tolerated after a single or multiple IV dose in mice and non-human primates. These results support the potential of this modality to expose all tumor lesions within a patient to a potently living drug that can both kill tumor cells and stimulate the immune system to fight cancer more effectively.

https://www.biospace.com/article/releases/oncorus-announces-publication-in-nature-communications-highlighting-the-development-of-its-intravenously-administered-synthetic-vrna-lnp-platform-for-the-treatment-of-cancer/

The Clinic Speaks Slowly, and Quietly

 BY DEREK LOWE

I sometimes feel as if I'm hammering away at a nail that's already well below the surface of the wood when I come around to today's topic, but then I realize that no, it really does need to be said. A lot of people really don't know how to deal with results from drug trials. That's especially true for the general public, of course, but it's more true than it should be for people in the field as well. Results that look promising can in fact evaporate on closer scrutiny, and this happens rather often. You can get the opposite, too, where something that didn't look good actually comes through. But those are more rare, since the odds are against any new treatment working at all (never forget the overall clinical failure rate of about 85%). The usual situation, sadly, is that if the results don't look worse in a larger trial or with more access to data, that's a win, and this is an outlook with current relevance.

These thoughts come up now in relation to molnupiravir. That's one of the many pandemic stories in the gigantic triple-decker novel that we've all been living in for the last couple of years, so here's a refresher for this particular plot thread. It's a small molecule aimed at viral polymerase activity, and it was discovered before the current coronavirus pandemic. At the time it was heading the clinic as a possible influenza drug, but it was rapidly repurposed to see if it could be useful against SAR-CoV-2. Most of these repurposing ideas are long shots, but in this case there was more hope, because molnupiravir seemed to have a broad spectrum of potent activity against viral polymerase enzymes. The initial Phase II data in the spring of 2021 were underwhelming, though. This was obviously not going to be a pandemic wonder drug, and the question became whether it was going to be of much use at all. 

But later that year the story flipped around: another trial showed what looked like strong evidence for efficacy, and optimism returned - for a bit. The subsequent FDA advisory committee meeting had more data available, though, and the more you looked at the results the less impressive they were. The problem was that the interim look at the trial data was quite different from the final numbers. Basically, the latter stages of the clinical trial were pretty terrible, and it dragged the overall efficacy numbers down into a real gray area. Keep in mind that all of these trials were in unvaccinated patients, too.

Molnupiravir got approved in the end, but with a real lack of enthusiasm. It and Pfizer's Paxlovid (a viral protease inhibitor) are still the main antiviral weapons, and from what I can see, molnupiravir is doing what business it does because of the ritonavir component in the Paxlovid dosing, which is given along with actual antiviral drug ingredient. Ritonavir is an inhibitor itself of a prime drug-metabolizing enzyme in the liver (CYP3A4), and without it you don't get much antiviral activity, because the protease inhibitor drug part of the combo (nirmatrelvir) is then chain-sawed in the liver and disappears rapidly. Problem is, there are a lot of other medications that are also cleared (at least in part) by CYP3A4, and their dosages and schedules are already built to take that into account. So patients who have some pre-existing conditions can face a real problem with Paxlovid -  it'll throw off all their other drug regimens - and some of them have been getting molnupiravir instead, particularly in Europe.

Is it doing them any good, though, in light of the disappointing overall data package? Well, we now have the results of a large controlled trial in the UK (thanks to Eric Topol of Scripps on Twitter for the notice). Update: for reason unknown to me (at least right now) this paper has been removed from the preprint server. It's a 25,000 patient adaptive trial design, open-label (which frankly tends to give you more optimistic-looking results in many cases than a double-blind). The participants were randomized to standard-of-care or that plus molnupiravir (800mg bid for five days, a course of treatment that 95% of them completed). Everyone in the trial was confirmed to have coronavirus infection, and the patients were either 50 or older, or 18 or older with comorbidities. 99% of them had had at least one coronavirus vaccination. The endpoint was straightforward: all-causes hospitalization or death within 28 days.

The overall hospitalization/death rates were low  - this isn't 2020, and the vaccinations really do have a strong effect on preventing those outcomes. But the rates of the control group and the +molnupiravir group were statistically identical. The latter had somewhat lower viral loads overall and slightly shorter times to recovery, and that's good, but it appears that molnupiravir is doing nothing to improve the (already low) number of previously-vaccinated patients who go on to experience serious disease. This is the first comprehensive look at this sort of population, and the first to study the situation with largely Omicron-infected individuals as well. And you'd have to say that the benefits are slight. Adverse events were very low and identical between the two groups.

How does this compare with the benefits of Paxlovid? Its data in unvaccinated patients definitely looked stronger than molnupiravir's in a similar population. I took the drug myself when I got infected back in May, having moved into the 60-and-over demographic with high blood pressure as well, judging that there was a reasonable chance of benefit with what seemed to be a low risk of adverse events. Unless you count the taste of the stuff, which is pretty darn adverse. But I didn't have as much data to back that up at the time. Just in the last few days, though, we've gotten some, and it's encouraging. This analysis of data from thousands of hospitals and clinics strongly suggests that Paxlovid does in fact reduce rates of hospitalization and death, and it does so both in vaccinated and unvaccinated patients. Now, this is observational data, so there are controls missing that would be present in an intentional trial, but everything at least is pointing in the right direction in a very large data set. And those benefits become more solid with increasing age of the patients, as you'd expect. So it looks like I made the right call in May, and it looks like Paxlovid is indeed a useful drug in older patients (but likely not in younger ones, unless they're also unvaccinated).

So the picture does seem to be coming into focus. Paxlovid is looking much more useful than molnupiravir, with the latter being (apparently) no use at all in preventing severe outcomes. But in order to get these results, you have to keep asking, and asking in as controlled and organized a fashion as you can manage, and in the largest population you can get. It's tedious and expensive and slow, isn't it? There are some ways to speed things up, no doubt, but none of them are going to be as fast as you'd hope. Real answers come hard.

https://www.science.org/content/blog-post/clinic-speaks-slowly-and-quietly

Hiding Inside Cells

 BY DEREK LOWE

Now here's one that you probably didn't see coming. As everyone knows, relapses after various types of cancer therapy are all too common. There are a lot of possible explanations for this, and a ready one is clonal selection. When you start sequencing solid tumors on a cell-by-cell level, you realize that many of them are a mass of competing lineages, formed as they inevitably throw off mutations. The belief (naturally enough) is that some of these are more targetable than others by a given therapy and will be killed off, which unfortunately clears the way for more resistant lines to prosper afterwards. (This is one of the several ways that oncology can resemble infectious disease work).

This situation certainly applies to classic chemotherapy regimes, and to the more recent immunotherapies as well. But there's something odd going on in that case, and this new paper has a rather startling explanation. As the authors note, these immune approaches target "neoantigens", peculiar proteins that mark off tumor cells from the normal background. These are no picnic to find and validate, but there are some known for particular tumors, of course. This work shows that you can use an immune-targeted approach in a mouse model of melanoma to almost completely wipe out the tumors while targeting the melanoma antigen TRP1. But after that happens, you actually get recurrance in many of the animals, producing tumors that are resistant to further treatment. But here's the weird part: these tumors have almost identical neoantigen profiles as compared to the original tumors. This behavior holds up across more than one immunotherapy route and more than one tumor type (breast versus melanoma, e.g.), and it seems to apply to human patient data as well. What's more, when you isolate cells from these second-wave tumors, they seem to be just as vulnerable to T-cell attack. So what's going on?

The evidence suggests that it's not something in the genetic lineage of these cells that is allowing them to survive, but rather some strategy that's used in vivo and might thus relate to something that occurs with multiple cells around rather than being dependent on the characteristics of individual ones. Looking at primary tumor tissue (either isolated ex vivo or via histology of the tumor itself) showed something quite odd. There were cells that appeared to have multiple nuclei, and closer inspection showed multiple membrane structures as well. What seems to be going on is tumor cells hiding inside other tumor cells. Injecting mice with two tumor cell lines, otherwise identical but labeled with two different fluorescent markers, illustrated this: cells formed that showed both of these colors simultaneously, one within the other. And the same behavior could be seen in the ex vivo cells - on standing, they formed these cell-in-cell structures. The cytoplasms don't mix; the two cells are still distinct.

Further experiments showed that it was the presence of T cells that led to this change, especially the CD8+ ones, and that STAT3 and EGR-1 are important pathways in the tumor cells during this behavior. Looking over different tumor types, colon and ovarian cancer cells almost always formed these things to survive T-cell conditions, while pancreatic and B-cell lymphomas never did, with other types on a spectrum between these. Immortalized non-tumor cells were just flat-out killed by T-cell treatment and did not form cell-in-cell structures. The authors emphasize that the great majority of cells are still killed by T-cell attack and that these cell types are transient, but that the survivors are disproportionately from the cell-in-cell population. These results hold up in human tumor tissue from patients with relapsing melanoma and other tumor types. It looks from further studies that it's not that the cell-in-cell structures completely evade T-cell attack, but rather that the "double layering" just buys them more time. T-cell derived lytic granules, which are doing the killing here, don't seem to make it to the inner cells.

This is pretty odd, and nothing quite like it seems to have been described before. Cell-in-cell behavior has been seen under other conditions, but it's generally associated with apoptosis or one cell flat-out consuming the other. This reversible they'll-never-find-me stuff, though, seems new. The authors suggest that immunotherapy be preceded clinically by STAT3 inhibition, and demonstrated that pretreatment with a known tool compound (Stattic) did indeed make the tumor cells notably more sensitive to T-cell attack. Definitely worth knowing about!

https://www.science.org/content/blog-post/hiding-inside-cells