Myovant Sciences and Pfizer Inc. announced that the U.S. Food and Drug Administration (FDA) has approved MYFEMBREE® (relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) as a one-pill, once-a-day therapy for the management of moderate to severe pain associated with endometriosis in pre-menopausal women, with a treatment duration of up to 24 months. The approval is supported by one-year efficacy and safety data, including 24-week data from the Phase 3 SPIRIT 1 and SPIRIT 2 trials, which were published in The Lancet, and the first 28 weeks of an open-label extension study for eligible women who completed either SPIRIT 1 or SPIRIT 2. MYFEMBREE also is approved for heavy menstrual bleeding associated with uterine fibroids in pre-menopausal women. Myovant and Pfizer will continue to jointly commercialize MYFEMBREE in the U.S. and product is available immediately. MYFEMBREE offers an effective, once-daily treatment option for the management of moderate to severe pain associated with endometriosis, with a treatment duration of up to 24 months. Endometriosis is a serious chronic condition that requires long-term interventions. Optimization of medical therapies is the recommended treatment paradigm. MYFEMBREE introduces an option for up to two years of pharmacological management of moderate to severe pain associated with endometriosis in pre-menopausal women. This approval is supported by one-year data from the Phase 3 SPIRIT program, which included two 24-week multi-national clinical studies (SPIRIT 1 and SPIRIT 2) in more than 1,200 women with pain associated with endometriosis, as well as the first 28 weeks of an open-label extension study to assess its longer-term use. Overall, these studies showed MYFEMBREE reduced menstrual pain and non-menstrual pelvic pain with a loss of mean bone mineral density of less than 1% from baseline through one year of treatment. SPIRIT 1 and 2 each met their co-primary endpoints with 75% of women in the MYFEMBREE group in both studies achieving a clinically meaningful reduction in dysmenorrhea compared with 27% and 30% of women in the placebo groups at Week 24, respectively (both p <0.0001). For non-menstrual pelvic pain, treatment with MYFEMBREE demonstrated a clinically meaningful reduction in pain in 59% and 66% of women, compared with 40% and 43% of women in the placebo groups (p < 0.0001). Adverse reactions occurring in at least 3% of women treated with MYFEMBREE and greater than placebo were: headache, vasomotor symptoms, mood disorders, abnormal uterine bleeding, nausea, toothache, back pain, decreased sexual desire and arousal, arthralgia, fatigue, and dizziness. The open-label extension study for eligible women who completed either SPIRIT 1 or SPIRIT 2 showed mean bone mineral density loss of less than 1% from baseline through one year of treatment; some patients (19.7%) had losses >3%. Annual bone density measurement is recommended while treating women for endometriosis. MYFEMBREE is available immediately to patients with moderate to severe pain associated with endometriosis with a prescription from their healthcare provider. Myovant and Pfizer also are committed to supporting women in the U.S. who are prescribed MYFEMBREE throughout their treatment journeys. The MYFEMBREE Support Program provides access support services, including insurance benefits checks, prior authorization support, co-pay support for commercially insured patients, and patient assistance for qualifying uninsured patients. Program terms and conditions apply. Indications and Usage: MYFEMBREE is indicated in premenopausal women for the management of: Heavy menstrual bleeding associated with uterine leiomyomas (fibroids); and Moderate to severe pain associated with endometriosis. Limitations of Use: Use of MYFEMBREE should be limited to 24 months due to the risk of continued bone loss which may not be reversible.
Saturday, August 6, 2022
FDA OKs Bayer Added Nubeqa Combo Indication for Prostate Cancer
Bayer announced the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for the oral androgen receptor inhibitor (ARi) NUBEQA® (darolutamide) with docetaxel for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC). The approval is based on results of the Phase III ARASENS trial that demonstrated a statistically significant increase in overall survival (OS), the trial's primary endpoint, with a reduction in the risk of death by 32% for those treated with NUBEQA plus androgen deprivation therapy (ADT) and docetaxel compared to ADT and docetaxel (HR=0.68, 95% CI 0.57-0.80; P<0.0001). Treatment with NUBEQA plus ADT and docetaxel also resulted in a statistically significant delay in time to pain progression (HR=0.79, 95% CI 0.66-0.95; P=0.006). About the ARASENS Trial: The ARASENS trial (NCT02799602) is the only randomized, Phase III, multi-center, double-blind, placebo-controlled trial prospectively designed to compare the use of a second-generation androgen receptor inhibitor (ARi) (NUBEQA) plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel to ADT and docetaxel (a guideline recommended treatment) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of NUBEQA twice a day or matching placebo, plus ADT and 75 mg/m2 of docetaxel, for 6 cycles. Treatment with NUBEQA plus ADT or ADT continued until symptomatic progressive disease, change of antineoplastic therapy, unacceptable toxicity, death, or withdrawal. The primary endpoint of this trial was overall survival (OS). Time to pain progression was a secondary endpoint. Permanent discontinuation of NUBEQA due to adverse reactions occurred in 14% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions which resulted in permanent discontinuation of NUBEQA were rash (1.1%), musculoskeletal pain (0.9%), and increased aspartate aminotransferase (AST) (0.9%). Dosage interruptions of NUBEQA due to adverse reactions occurred in 23% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions (>2%) requiring dosage interruption of NUBEQA were increased alanine aminotransferase (ALT) (3.2%), increased AST (3.1%) and febrile neutropenia (2.1%). Dosage reductions of NUBEQA due to adverse reactions occurred in 9% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions (>2%) requiring dosage reduction of NUBEQA were increased ALT (2.8%) and increased AST (2.5%). The most common adverse reactions (=10% with a =2% increase over placebo with docetaxel) were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (=30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia.
Senate rules official strikes part of Dem drug pricing measures
Democrats’ sweeping economic package was narrowed somewhat on Saturday after a ruling from a top Senate rules official struck one of the provisions aimed at lowering prescription drug prices.
The Senate parliamentarian, an official who determines whether provisions meet the chamber’s complicated budget rules, struck down part of a provision that would limit drug companies’ price increases to the rate of inflation.
Senate Democrats had proposed requiring drug companies to pay rebates back to the government if their prices rose faster than the rate of inflation, both in Medicare and in the private health insurance market.
The parliamentarian allowed the provision to stand in Medicare but struck it for people with private health insurance, such as those who get coverage through their jobs, a substantial chunk of the population.
Still, as expected, the parliamentarian allowed to stand Democrats’ signature drug pricing measure, which would for the first time allow Medicare to negotiate lower drug prices on some drugs.
The parliamentarian also allowed to stand Democrats’ clean energy tax package. Other parts of the package are still awaiting rulings, including a $35 cap on what patients have to pay out of pocket for insulin.
“Democrats have received extremely good news: for the first time, Medicare will finally be allowed to negotiate prescription drug prices, seniors will have free vaccines and their costs capped, and much more,” Senate Majority Leader Charles Schumer (D-N.Y.) said in a statement. “This is a major victory for the American people. While there was one unfortunate ruling in that the inflation rebate is more limited in scope, the overall program remains intact and we are one step closer to finally taking on Big Pharma and lowering Rx drug prices for millions of Americans.”
The provisions are being judged on whether they have a sufficiently substantial impact on the federal budget. The rules stem from the special procedure Democrats are using for their package to avoid a GOP filibuster called budget reconciliation.
The end result is that the drug pricing savings included in the package are even more focused on seniors on Medicare and largely do not touch people with private health insurance.
Dems have to limit their drug pricing reforms to Medicare to comply with Senate rules
Democrats will likely have to axe two provisions from their drug pricing plan to fit in with Senate rules, both of which would have brought down drug prices for people who get health insurance through their jobs.
Democrats had hoped to cap insulin costs for patients with employer-sponsored health insurance in the massive climate, tax and health bill they’re hoping to advance as soon as this weekend. They also wanted to protect the same pool of people, who get health insurance through their jobs, from bearing the brunt of future drug price hikes.
But the Senate’s rules referee said early Saturday that neither would be allowed under the complicated rules that govern the fast-track process Democrats are using to pass the package without Republican support, according to both public statements and a Senate aide who shared further details.
The parliamentarian also ruled that Democrats have to tweak an enforcement mechanism for their Medicare negotiation process, a separate Senate aide said, but it likely won’t have much practical impact.
The changes likely won’t affect Democrats’ unanimous support for the bill, but they significantly narrow the number of people who will actually benefit from the prescription drug pricing reforms. The Senate is planning to begin voting on the package as soon as Saturday. Now, the package will likely only lower drug prices for people who are covered by Medicare.
The narrowing of the package is a mixed bag for the pharmaceutical industry, which has been lobbying hard to try to convince Democrats to oppose it. They are staunchly against the broadest reform in the bill, its mechanism for allowing Medicare to negotiate drug prices. They also opposed the way Democrats had hoped to protect commercially insured patients from price hikes, but capping patients’ out-of-pocket costs for insulin would have been good for the industry.
Here’s a summary of the changes to Democrats’ drug pricing proposal.
Democrats originally engineered their penalties for drugmakers that hike prices quickly to try to mitigate the effects on the private insurance market, but their solution didn’t fly with the parliamentarian.
Employers had been concerned that if Congress suppressed prices and price growth in Medicare, drug makers would simply inflate costs in the private sector to make up for the difference.
To minimize that possibility, Democrats crafted a formula that incorporated the prices of drug units sold in the private sector to determine how much of a penalty drug makers would have to pay if they hiked prices faster than inflation.
However, the parliamentarian ruled that strategy wasn’t allowable under the rules, and the policy will have to be limited to drugs sold to Medicare patients.
Democrats’ last-ditch efforts to salvage some insulin pricing policy this week had mixed success — they managed to insert insulin cost protections that would cap the drug’s price at $35 per month for Medicare patients. But the parliamentarian ruled against a separate policy that aimed to cap the price for patients in the private insurance market, a Senate aide said.
The commercial market out-of-pocket cap was disallowed because it didn’t have enough of an effect on the federal government. It’s unclear whether Democrats will remove the commercial market insulin cap from the legislation themselves, or force a vote on the Senate floor.
The failure to provide any relief for diabetes patients outside of Medicare would be the latest blow to Democrats’ dizzying strategy to try to get something to show for themselves on insulin pricing, the poster child for perverse pricing incentives, before the midterm elections.
Moderate Democrats, including Sen. Kyrsten Sinema (D-Ariz.), have been pushing to cap insulin costs at $35 per month for patients with private insurance for months, including in an earlier reconciliation effort last fall. After that iteration went up in flames, Sen. Raphael Warnock (D-Ga.) introduced the insulin cost caps as a standalone bill.
But to advance the insulin cap on its own, supporters would have to garner the support of Republicans in the Senate. And though Republicans have supported caps on out-of-pocket costs before, it became clear that they likely couldn’t stomach giving a political win to the most vulnerable Democratic senators in an election year.
Instead of forcing Democrats to vote on Warnock’s bill, Senate Majority Leader Chuck Schumer (D-N.Y.) decided to pivot and bless negotiations between Senate Diabetes Caucus Co-Chairs Susan Collins (R-Maine) and Jeanne Shaheen (D-N.H.), who came up with a different way to try to rein in insulin costs.
But that measure failed to gain sufficient support, too, so Democrats turned to a last-ditch effort to cram as much insulin policy as they could into their reconciliation bill to work around Republicans’ opposition.
Democrats’ Medicare negotiation process for prescription drugs survived mostly intact, except for a tweak to the enforcement mechanism to force drug makers to comply.
The original policy was structured as an excise tax on drug makers who didn’t cooperate that over time could rise to 95% of a drug’s sales. However, congressional budget analysts had predicted that the tax wouldn’t actually generate any new money for the government, as a drug maker would almost certainly rather remove their drug from the Medicare program than pay the tax.
Democrats had to allow drug makers that refuse to sell drugs to Medicare at negotiated prices sidestep the big tax penalty — but they’d have to pull all of their drugs out of the program, according to a Senate aide.
https://www.statnews.com/2022/08/06/democrats-limit-drug-pricing-reforms/
U.S. Automakers Say 70% of EV Models Would Not Qualify for Tax Credit Under Senate Bill
Most electric-vehicle models would be ineligible for a $7,500 tax credit for U.S. buyers under a Democratic proposal in the U.S. Senate, a group of major automakers said on Friday.
Automakers have been privately expressing concern about the proposal's increasing requirements for vehicles' batteries and critical-mineral contents to be sourced from the United States.
John Bozzella, heads of the Alliance for Automotive Innovation that represents General Motors, Toyota Motor, and Ford Motor among others, said a July 27 proposal by Senators Chuck Schumer and Joe Manchin would make 70% of 72 U.S. electric, plug-in hybrid and fuel-cell EVs ineligible upon passage.
"None would qualify for the full credit when additional sourcing requirements go into effect," he said.
Car makers want significant changes to the proposal, which is part of a larger drug pricing, energy and tax bill.
Without the tax credit, the vehicles become more costly for American consumers, and this could impact demand and sales. It could also slow progress toward President Joe Biden's target to have half of all new vehicles sold be electric or plug-in hybrid models in 2030.
An analysis by the Congressional Budget Office on Wednesday suggested just 11,000 new EVs would use the credit in 2023.
Manchin and Schumer's offices did not immediately comment. The Senate could vote as soon as Saturday on the bill.
"I don't believe that we should be building a transportation mode on the backs of foreign supply chains," Manchin said on Tuesday.
The bill includes rising requirements for the percentage of battery components originating from North America based on value. After 2023, it would disallow batteries with any Chinese components.
"A more gradual phase-in of the battery component, critical mineral and final assembly requirements – that better reflect current geopolitical, sourcing and mineral extraction realities – will preserve the credit for millions of Americans," Bozzella wrote.
Automakers want to expand countries from which batteries, battery components and critical minerals can be sourced to include NATO members, Japan and others.
The new EV tax credits, which would expire at the end of 2032, would be limited to trucks, vans and SUVs with suggested retail prices of no more than $80,000 and to cars priced at no more than $55,000. They would be limited to families with adjusted gross incomes of up to $300,000 annually.
Two New Triggers for Alzheimer's Identified
Researchers from Tufts University and the University of Oxford have found that two common viruses—the varicella zoster and herpes simplex viruses—likely constitute a pathway that leads to Alzheimer's disease.
Their findings, published Tuesday in the Journal of Alzheimer's Disease, suggest that when varicella zoster viruses infect neurons, they trigger an inflammatory response characterized by a surplus of secreted cytokines. In turn, this awakens herpes simplex viruses, which typically lie dormant and harmless in the brain. With both viruses now active, inflammation throughout the brain is aggravated, potentially leading to the formation of plaque and the slow deterioration of neurons—both hallmarks of Alzheimer's.
The research team generated these data by using cultures of neural stem cells, which are able to grow and form networks in the lab as they would in the brain. Interestingly, they found that infecting neurons with varicella zoster alone was not enough to trigger Alzheimer-like properties in their setup. When herpes simplex was already lying in wait, varicella zoster initiated a cascade of events that culminated in plaques, tangled fibers and brain damage.
"It's a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble," Dana Cairns, research associate at the Biomedical Engineering Department of Tufts, said in a statement. Cairns is the study's lead author. One of their collaborators, Oxford's Ruth Itzhaki, was one of the first scientists to suggest a link between herpes infections and Alzheimer's.
HSV-1, the subtype of the herpes simplex virus thought to be involved in Alzheimer's, causes both oral and genital herpes. It is a very common infection, affecting nearly 4 million people worldwide under the age of 50 years. The American Sexual Health Organization estimates that around one in two adults has oral herpes in the United States.
Varicella zoster, the other half of the pathway uncovered by Cairns' group, is also an extremely common virus. The first infection with varicella zoster causes chickenpox, but after that's cured, the virus tends to linger in peripheral nerves. When these quiescent viruses are reactivated, they cause shingles.
Those highly prevalent viruses could lead to Alzheimer's doesn't bode well for a therapeutic space that has of late been strapped with trial failures and scientific scandals.
Earlier this week, Roche subsidiary Genentech and its partner AC Immune had to dig deep into Phase II data after their candidate, crenezumab, fell short of its primary endpoint in patients with autosomal dominant Alzheimer's disease. Failing to show significant superiority over placebo in cognitive and memory measures, the companies instead diverted attention toward a positive trend in the data and blamed the lack of statistical significance on what AC Immune called "a confluence of factors."
Even the first-ever drug approved for Alzheimer's, Biogen's Aduhelm (aducanumab), has had a difficult time taking off, with many skeptics questioning its efficacy. In June this year, following drastically curtailed insurer coverage of their drug, the company decided to let go of a post-market real-world analysis of Aduhelm. A Phase IV confirmatory trial is pushing through.
Aside from major medication misses, allegations of data falsification have also rocked the Alzheimer's space. At the center of one such controversy is the Texas biotech Cassava Sciences, which last month had a DOJ investigation opened against it. The probe will focus on claims that the company had doctored data to support its Alzheimer's drug simufilam. Cassava has been embroiled in this matter for almost a year now.
Alongside the Cassava controversy is another that casts doubt on a seminal 2006 paper, published in the prestigious medical journal Nature. Science sleuths have found evidence that Western blot photos were manipulated, calling into question the role of Aβ*56—an amyloid-β oligomer—in the signature memory loss tied to Alzheimer's.
https://www.biospace.com/article/common-viruses-could-trigger-alzheimer-s-new-study-suggests/
A year out from the new payroll tax collection, WPC releases study shows WA Cares program failing
Today WPC released Center for Health Care Director Elizabeth Hovde's new extensive study on the state's long-term-care program, WA Cares. It reveals a program working against the inspiration for its existence -- the need for people to prepare for long-term-care needs -- with marketing that assures people that the new program will give the financial freedom when it will not. Ironically, the new state program is encouraging people to ignore preparing for possible long-term-care needs despite having a benefit that is not only already wildly insufficient for long-term care, but which will have to be cut (or the payroll tax that funds it will need to be raised), in order for the program to remain solvent.
The study also shows that the state's cost-savings are miniscule (and questionable) compared to what Washington workers will be paying in the tax.
I've posted some takeaways I had from the study below. I urge you to take a look at them and consider reading the full Policy Brief. Don't keep the information to yourself! Share the points that strike you with everyone you know!
Key Takeaways:
- The WA Cares program is insolvent before it begins, facing a $15 billion shortfall.
- Between 2022-2053, workers will pay more than $30 billion for the state to realize net savings of just over $1.2 billion, assuming administrative costs don't increase.
- The regressive tax in the law means some low-income workers will be forced to hand over a portion of their income to benefit others with higher incomes.
- It is likely the Employment Security Department will grant a monopoly to Service Employees International Union 775 (among the largest campaign donors in the state) to provide required training of family caregivers who could be obligated to pay them dues.
- The lifetime benefit of $36,500 is highly unlikely to provide for most people's needs, making the state's promises of financial security and "peace of mind" both false and dangerous.
- There is already legislative discussion that the 58-cent tax will need to increase or the benefit amount of $36,500 decrease to keep the program viable.
- At its starting tax rate (already expected to increase), a worker earning $25,000 will pay $145 each year, a worker making $50,000 will pay $290, those making $100,000 will pay $580 and so on.
- Private long-term-care plans typically start paying out when an elderly person needs help with two daily-life activities, while the state program will require a person to need help with at least three.