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Monday, April 1, 2024

Lack of Medicare Coverage for GLP-1 Drugs Tied to Lower Prescription Rates: Study

 Medicare policy prohibiting the coverage of GLP-1 receptor agonists for obesity may be driving lower prescription and initiation rates of these therapies in adults aged 65 to 69 years, according to a study preprint from the University of Pennsylvania and healthcare data firm Truveta Research.

Using de-identified health record data from Truveta, the study—published Thursday on the preprint server medRxiv—found nearly 414,000 adults between 60 to 69 years of age who were overweight or obese but without type 2 diabetes and were eligible for GLP-1 RA treatment. However, of these seniors, fewer than 1%--or just over 1,200—were actually prescribed these anti-obesity medications.

Prescription rates were even lower among Medicare-aged patients. In the subgroup of patients aged 65 to 69 years, only 0.24% of eligible patients were prescribed GLP-1 treatments, compared to 0.37% in counterparts who were 60 to 64 years old. The absolute difference of 0.13% was statistically significant, with a p-value less than 0.01, according to the study.

Medicare-aged patients also saw a lower rate of dispensing, with 15.2% filling their prescriptions within 60 days, as opposed to 22.7% in the younger age group.

“These findings suggest that Medicare-aged adults face unique gaps in access, occurring at both the medication prescribing and filling stages,” the researchers wrote, adding that this effect could likely be driven by “a lack of coverage.”

Offering Medicare coverage of GLP-1 receptor agonist anti-obesity medications “has the potential to increase prescribing and initiation substantially,” the researchers argue, while acknowledging that more research needs to be done “to understand tradeoffs between increased prescribing costs and potential reductions” in major adverse cardiovascular events and improvements in quality of life.

The Truveta study comes one week after the Centers for Medicare and Medicaid Services announced that it will cover Novo Nordisk’s weight-loss treatment Wegovy (semaglutide) for its use in reducing the risk of heart attack, stroke and other related cardiovascular problems in patients with pre-existing heart conditions.

However, Medicare will still not cover Wegovy when used for weight loss.

Medicare’s decision to expand its coverage for Wegovy follows an analysis by the Congressional Budget Office (CBO), which predicted that the Department of Health and Human Services will negotiate the prices for semaglutide under the Inflation Reduction Act “within the next few years.”

However, at its current monthly cost of around $1,000 to $1,300, Medicare still cannot sustainably cover GLP-1 treatments, though the negotiations are likely to bring prices down, according to the CBO’s analysis. Generic competition and next-generation weight-loss medications will also likely lower the costs of current anti-obesity drugs, the CBO contends.

The FDA last month expanded Wegovy’s label, allowing the use of the GLP-1 RA in conjunction with diet and exercise to cut cardiovascular risks.

https://www.biospace.com/article/lack-of-medicare-coverage-for-glp-1-drugs-tied-to-lower-prescription-rates-study/

Biogen and Eisai Fall Behind on Leqembi’s Subcutaneous BLA for Alzheimer’s

 Biogen and Eisai on Monday announced that they have missed their March 2024 target of filling a Biologics License Application for a subcutaneous formulation of their Alzheimer’s disease therapy Leqembi (lecanemab), being proposed as a weekly maintenance regimen.

The companies initially planned to start a rolling Biologics License Application (BLA) last month under the existing Fast Track and Breakthrough Therapy designations for Leqembi. However, the regulator informed Eisai that they would need a Fast Track designation specifically for the subcutaneous formulation before they can launch their rolling application, according to Monday’s announcement.

Eisai has since submitted a request for the Fast Track designation and is set to receive a verdict within 60 days of its filing. If granted, the partners will launch their rolling BLA.

The companies also announced that they have filed a supplemental BLA (sBLA) proposing a monthly intravenous maintenance dosing schedule for Leqembi. If approved, this maintenance regimen will be available for patients who complete the biweekly intravenous initiation phase, though the exact duration for this is still under discussion with the FDA.

Currently, Leqembi is approved as an intravenous infusion given over approximately one hour, every two weeks, according to its label.

Leqembi’s monthly infusion schedule is designed to sustain effective drug levels in the body, enough to keep the toxic protofibrils at bay. In patients with Alzheimer’s disease, these protofibrils can still trigger neuronal damage and brain injury even amyloid-beta plaques have been removed, according to the companies.

Biogen and Leqembi are supporting the sBLA with modelling data from results of the Phase IIb Study 201 and its open-label extension phase, as well as the Phase III Clarity AD study and its open-label extension.

Leqembi is a humanized IgG1 monoclonal antibody that works by targeting aggregated soluble and insoluble amyloid-beta plaques. This mode of action helps clear these clumps from the brain, which would otherwise interfere with cognition and give rise to the hallmark symptoms of Alzheimer’s disease.

Based on data from Study 201, which showed that Leqembi could decrease the levels of amyloid-beta plaques in the brain, the FDA granted Leqembi accelerated approval in January 2023. In July 2023, the regulator converted its nod into a full approval, making Leqembi the first anti-amyloid antibody to earn this distinction.

Leqembi’s traditional approval was based on the Clarity AD, which demonstrated that the biomarker effects observed in Study 201 translated to clinical benefits. Patients treated with Leqembi saw a 27% reduction in clinical decline versus placebo, as defined by the Clinical Dementia Rating-Sum of Boxes test.

https://www.biospace.com/article/biogen-and-eisai-fall-behind-on-leqembi-s-subcutaneous-bla-for-alzheimer-s/

Bristol Pulls Ahead of Amgen, Aces Confirmatory Phase III NSCLC Trial for Krazati

 Bristol Myers Squibb on Thursday released results from the Phase III KRYSTAL-12 study, showing that Krazati (adagrasib) met its primary efficacy endpoint of progression-free survival in patients with locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations.

The pharma did not provide specific data in its announcement but said that when used in the second-line setting or later, Krazati treatment led to “statistically significant and clinically meaningful” improvements in progression-free survival (PFS) versus standard-of-care chemotherapy. The KRAS blocker also elicited a significantly better overall response rate than chemotherapy.

In terms of safety, KRYSTAL-12 found no new signals of concern and Krazati’s adverse event profile was consistent with what had previously been established in prior trials.

Abderrahim Oukessou, global program lead of Krazati at BMS, in a statement called KRYSTAL-12’s findings “an important reinforcement” of the role of Krazati in treating advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC).

“Topline results of the KRYSTAL-12 confirmatory study will build greater trust in the medical and patient community,” Oukessou said.

BMS is still currently conducting a full analysis of KRYSTAL-12’s data and will share its findings with the scientific community at an upcoming medical congress. The pharma will also submit these data to health authorities.

Originally developed by Mirati, Krazati is a covalent and irreversible inhibitor of the KRAS G12C, locking the mutant protein in its inactive state and blocking its downstream signaling, without negatively affecting the wild-type protein. This mechanism of action allows Krazati to prevent the hyperactive growth of cancer cells without causing damage to healthy cells.

BMS gained access to Krazati in October 2023, when it bought Mirati for $4.8 billion.

Krazati first won the FDA’s approval in December 2022 for the treatment of adult patients with metastatic or locally advanced NSCLC harboring the KRAS G12C mutation, as determined by an FDA-approved test. Krazati is only indicated for patients who have undergone at least one prior line of systemic therapy.

This regulatory victory came via the FDA’s accelerated approval pathway, for which Mirati ran KRYSTAL-12 as a confirmatory study to keep Krazati on the market.

With the data from KRYSTAL-12, BMS now pulls ahead of Amgen which in December 2023 failed to secure the FDA’s full approval for its own KRAS blocker Lumakras (sotorasib). In October 2023, the FDA’s Oncologic Drugs Advisory Committee voted against the approval of Lumakras, pointing out that the data from the company’s CodeBreaK 200 study could not be reliably interpreted.

In its Complete Response Letter, the FDA noted that Amgen must complete an additional confirmatory study no later than February 2028 to support Lumakras’ full approval.

https://www.biospace.com/article/bms-pulls-ahead-of-amgen-aces-confirmatory-phase-iii-nsclc-trial-for-krazati/

AstraZeneca Gets FDA Approval in Boost to Rare Disease Franchise

 AstraZeneca announced Monday that it has secured FDA approval for an add-on to its blockbuster rare disease franchise, providing a potential differentiator as it tries to hold off competition from Novartis, Roche and biosimilars.

The approval covers danicopan, an oral, first-in-class factor D inhibitor that AstraZeneca’s rare disease unit has developed as a treatment for a subset of adults with paroxysmal nocturnal haemoglobinuria (PNH). The FDA approved the drug as an add-on therapy for AstraZeneca’s Ultomiris (ravulizumab) and Soliris (eculizumab).

Between 10% and 20% of PNH patients experience clinically significant removal of red blood cells outside of the blood vessels, a condition called extravascular haemolysis (EVH), and continued anemia symptoms when taking C5 inhibitors such as Ultomiris and Soliris. People with EVH can require blood transfusions to manage the condition.

Danicopan, which AstraZeneca will market as Voydeya, is designed to reduce the need for transfusions and otherwise improve outcomes in EVH patients. AstraZeneca validated danicopan in a Phase III clinical trial that linked the factor D inhibitor to a statistically significant improvement in hemoglobin levels after 12 weeks. Later, the drug developer showed the improvements persisted through 48 weeks.

Alexion added danicopan to its pipeline when it paid $930 million for Achillion Pharmaceuticals in 2019. Ownership of the drug molecule changed again after AstraZeneca agreed to buy Alexion for $39 billion in 2020.

Buying Alexion gave AstraZeneca a PNH franchise. Alexion had the PNH market largely to itself for years, helping it to turn Soliris and Ultomiris into blockbusters, but the landscape is shifting. Alexion CEO Marc Dunoyer named the introduction of Soliris biosimilars as the main headwind facing the business on an AstraZeneca earnings call in February 2024.

AstraZeneca is working to transition patients from Soliris to Ultomiris to soften the impact of biosimilars on sales. Conversion of Soliris to Ultomiris in PNH is “in the magnitude of 80%,” Dunoyer said. Sales of Soliris fell 16% to $3.1 billion last year, while sales of Ultomiris rose more than 50% to almost $3 billion.

In addition, AstraZeneca faces branded rivals for the PNH market. Apellis brought Empaveli (pegcetacoplan) to market in 2021. Novartis won FDA approval for the factor B inhibitor Fabhalta (iptacopan) late last year after linking it to improved outcomes in patients who had residual anemia, while receiving a stable regimen of an anti-C5 therapy such as Soliris or Ultomiris. Roche has filed for approval of a C5 drug.

https://www.biospace.com/article/astrazeneca-gets-fda-approval-in-boost-to-blockbuster-rare-disease-franchise/

Trump popularity growing among black, latino voters, revived effort to paint him as racist

 In a Monday 'exclusive' report, Axios is absolutely beside themselves, writing "Trump allies plot anti-racism protections — for white people" (emphasis ours).

There's a plot afoot!

Trump's Justice Department would push to eliminate or upend programs in government and corporate America that are designed to counter racism that has favored whites.

Does racism still favor whites? Last we checked, white people, particularly white men - who 'toxically mansplain' everything, are the scourge of the universe.

Oh.

Anyhow, Axios has presented quite the narrative; the Trump campaign's longstanding promise to eliminate Biden DEI initatives + efforts by Trump allies to legally combat anti-white racism "with the Supreme Court's turn to the right" = racism.

First, here's what Trump said last year: 

"Every institution in America is under attack from this Marxist concept of 'equity,'" adding "I will get this extremism out of the White House, out of the military, out of the Justice Department, and out of our government."

Trump campaign spox Steven Cheung told Axios: "As President Trump has said, all staff, offices, and initiatives connected to Biden's un-American policy will be immediately terminated," adding "President Trump is committed to weeding out discriminatory programs and racist ideology across the federal government."

This is apparently a very bad thing.

Longtime aides and allies preparing for a potential second Trump administration have been laying legal groundwork with a flurry of lawsuits and legal complaints — some of which have been successful.

  • A central vehicle for the effort has been America First Legal, founded by former Trump aide Stephen Miller, who has called the group conservatives' "long-awaited answer to the ACLU."
  • America First cited the Civil Rights Act of 1964 in February in a lawsuit against CBS and Paramount Global for what the group argued was discrimination against a white, straight man who was a writer for the show "Seal Team" in 2017. -Axios

Axios then picks what we can assume they consider to be the most racist example - the February filing of a civil rights complaint against the NFL over the "Rooney Rule," which America First says violates "Title VII of the Civil Rights Act of 1964 and engaging in race and sex discrimination," as the purpose of the 2003 rule was "increas[ing] the number of minorities hired in head coach, general manager, and executive positions," to address "the historically low number of minorities in head coaching positions."

The Rooney Rule has been amended several times since its adoption and now requires teams to interview at least two external minority candidates for head coach and general manager vacancies, at least one external minority for a coordinator job, and at least one minority and/or female candidate for senior level positions, such as club president and senior executives.

Effectively, in the twenty years that the Rooney Rule has been in existence, all it has done – according to minority interviewees for head coaching positions and the former head of the NFL Players Association DeMaurice Smith – is result in member clubs engaging in sham interviews with minority candidates solely to check the Rooney Rule box. Given the limited timeframe to hire executives and coaches after the season, this results in fewer opportunities for similarly situated, well-qualified candidates who are not minorities. -America First Legal

Meanwhile, Axios notes that the Heritage Foundation's "well-funded "Project 2025"" is "preparing for a future Trump Justice Department to implement — or challenge — policies on a broader scale."

Part of the plan, written by former Trump DOJ official and America First's general counsel Gene Hamilton, argues that "advancing the interests of certain segments of American society ... comes at the expense of other Americans — and in nearly all cases violates longstanding federal law."

Efforts to combat anti-white racism have been successful, because of, recall, the Supreme Court's "turn to the right" - so, extra racist.

  • In 2021, a federal judge blocked a $4 billion program to help Black farmers.
  • Earlier this month, another federal judge ruled that the Commerce Department's Minority Business Development Agency was discriminating against white people and that the program had to be open to everyone. -Axios

Heaven forbid people be judged by the content of their character.

Who do they think they're fooling? Oh right.

 https://www.zerohedge.com/political/left-livid-over-trump-ally-efforts-eliminate-anti-white-policies

ZimVie Announces Closing of Sale of Spine Business

 ZimVie Inc. (Nasdaq: ZIMV), a global life sciences leader in the dental market, today announced that it has closed the previously communicated sale of its Spine business to an affiliate of H.I.G. Capital for $375 million in total consideration, including $315 million in cash and a $60 million promissory note.

“The completion of the sale of our Spine business is the culmination of months of partnership with H.I.G. Capital and years of commitment from our global Spine team members; I would like to thank everyone for their immense contributions,” said Vafa Jamali, President and Chief Executive Officer. “I could not be more excited for the future of our company as we continue to invest in differentiated solutions for Dental patients and providers in our most attractive end markets, while optimizing our structure to deliver value for our shareholders.”

Terms of the Agreement

Under the terms of the agreement, ZimVie will receive $375 million in total consideration, comprised of $315 million in cash, subject to certain customary adjustments as set forth in the agreement, and $60 million in the form of a promissory note that will accrue interest at a rate of 10% per annum, compounded semi-annually, payable in kind, subject to a maturity no later than five and a half years from today’s closing.

Outlook for ZimVie

As previously communicated, ZimVie expects to achieve an annualized financial profile of $455+ million in Net Sales, and a 15%+ adjusted EBITDA margin(1) one year following the close of the deal. ZimVie intends to immediately pay down $275 million of outstanding debt, leaving total debt of approximately $234 million, and estimated cash of approximately $66 million as of April 2, 2024.

https://www.globenewswire.com/news-release/2024/04/01/2855117/0/en/ZimVie-Announces-Closing-of-Sale-of-Spine-Business.html

Solid Biosciences Receives Rare Pediatric Disease Designation for Duchenne

  SGT-003 Granted Rare Pediatric Disease, Orphan Drug and Fast Track Designations in U.S. –

– Site initiations scheduled for April; patient dosing expected to begin in Q2 2024 –

https://www.globenewswire.com/news-release/2024/04/01/2855112/0/en/Solid-Biosciences-Receives-Rare-Pediatric-Disease-Designation-from-the-FDA-for-Duchenne-Muscular-Dystrophy-Gene-Therapy-Candidate-SGT-003.html