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As we gear up for Friday's advisory committee hearing to review the confirmatory trial for Eisai's new Alzheimer's drug Leqembi, it's hard not to look at the draft committee roster, with just 6 voting members, and wonder why there are so few experts at this meeting. Feel free to respond to this email with your thoughts on the last time an adcomm had fewer than 10 voting members. |
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Zachary Brennan |
Senior Editor, Endpoints News
@ZacharyBrennan
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by Zachary Brennan
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The FDA said Wednesday that the confirmatory trial that Eisai and Biogen ran to show their new Alzheimer's drug has a clinical benefit did indeed have one, lining Leqembi up for a likely full approval next month after getting an accelerated nod in January. Ahead of Friday's advisory committee meeting, FDA reviewers affirmed what Eisai and Biogen said at the time about the results of the confirmatory trial, known as CLARITY AD, adding that: |
Any group-level mean change from baseline on the CDR-SB that is reduced, to a statistically significant extent in an appropriately powered study, compared to placebo is considered clinically meaningful. |
| The agency also said that the positive finding on the primary endpoint is supported by statistically significant results for all four multiplicity-controlled secondary endpoints, "including clinical endpoints capturing distinct information regarding cognitive decline." As far as safety-related issues, which include amyloid-related imaging abnormalities (ARIA), cerebral hemorrhage, and infusion-related reactions and hypersensitivity, the FDA reviewers sounded positive again, saying the "risks do not appear to preclude traditional approval. Risk can be mitigated through a description in labeling and recommendations for monitoring and dose management guidelines as provided for in labeling." A positive vote will likely mean a swift full approval and wider coverage from both the CMS and private insurers, which until now have limited the use of Leqembi and Biogen's Aduhelm to clinical trials despite their accelerated approvals. CMS recently said it plans to cover Leqembi if it receives full approval. The drug's PDUFA date is July 6. |
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by Zachary Brennan
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The FDA's advisory committees of outside experts are supposed to offer the agency with unbiased reviews of the sponsor's efficacy and safety data before them. And while occasionally the FDA will allow certain tangentially paid consultants (e.g. from a competing firm), those relationships must be disclosed ahead of time, and waivers from that COI need to be granted. In the case of David Weisman, a neurologist with Pennsylvania-based Abington Neurological Associates who worked on clinical trials for Eisai and Biogen, the FDA had sought his expertise in Friday's adcomm that will discuss whether to convert Eisai's new Alzheimer's drug Leqembi (lecanemab) into a full approval. The decision is likely to be one in favor of Leqembi, opening the door for wider sales nationwide with CMS coverage. The only issue with Weisman's participation in the meeting, as explained in his waiver to participate, is that he's received tens of thousands of dollars from Eisai and partner Biogen over the last five years, and been vocal about his support for lecanemab, making his impartiality a question mark. And while the FDA praised how he is "highly respected internationally for his deep insights and broad perspectives, and he has been highly valued as a member of the Peripheral and Central Nervous System Drugs Advisory Committee" as recently as March to discuss Biogen's tofersen, a treatment of ALS approved in April, others wondered if there were not better options. Weisman announced on Twitter today that he would not participate in the panel. |
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Chiquita Brooks-LaSure, Centers for Medicare and Medicaid Services administrator (AP Photo/Evan Vucci) |
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by Zachary Brennan
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As Congressional and advocacy group pressure has been heated, the Centers for Medicare and Medicaid Services reaffirmed today that if amyloid-targeted drugs to slow the progression of Alzheimer’s disease win full approval — not just accelerated approval — then Medicare will cover treatment where real-world data can be collected. The official coverage-is-coming announcement, which had been previously mentioned by Eisai, Biogen and CMS officials separately, arrives as Eisai and Biogen's Leqembi (lecanemab) faces an advisory committee meeting of outside FDA experts next Friday. That same FDA adcomm previously voted unanimously against the approval of Biogen's other amyloid-targeted drug Aduhelm (aducanumab), which still went on to win an accelerated approval in 2021. Three members of the committee, including Washington University in St. Louis' Joel Perlmutter, Harvard's Aaron Kesselheim and the Mayo Clinic's David Knopman resigned after the FDA made its accelerated approval decision. But Aduhelm still faced CMS' negative coverage determination — which so far has applied to all amyloid-targeted drugs under accelerated approval — that there would be no coverage outside of clinical trials. Aduhelm has gone on to muster minimal sales. But Leqembi may be different. After receiving accelerated approval in January, the drug will likely be the first to win full approval on or before July 6, depending on the results of next week's adcomm. "If the FDA grants traditional approval CMS is prepared to ensure anyone with Medicare Part B who meets the criteria is covered," CMS chief Chiquita Brooks-LaSure said in a statement. |
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FDA Commissioner Robert Califf (Tom Williams/CQ Roll Call via AP Images) |
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by Nicole DeFeudis
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FDA Commissioner Rob Califf told BIO CEO Rachel King on Wednesday that it’s “impossible to argue that the US is doing well in health,” highlighting high drug prices and misinformation as two key challenges. The commissioner also took the opportunity to discuss accelerated approval reforms, attrition at the agency and the Inflation Reduction Act, which came into focus earlier this week when Merck filed a lawsuit calling parts of the drug pricing law a sham. Industry critics have argued that the legislation will have a chilling effect on innovation. When asked about the IRA, Califf responded that “the prices of drugs are too high.” “We have to come up with a better system. And the IRA is an effort to do that,” he said, later adding that “all of these big laws have imperfections,” but he’s “not at liberty to talk about specific details of what I think is imperfect.” He discussed ramping up communications with CMS, not just as part of the IRA, but “on multiple fronts.” “There’s something missing in the equation by which we translate all this amazing innovation into products and services that help the population,” he said. CMS said earlier this year that it intends to work closely with the FDA on accelerated approval payment reforms in a pilot program designed to “reduce Medicare spending on drugs that have no confirmed clinical benefit.” |
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by Andrew Dunn
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Merck has filed a lawsuit in federal court to try and invalidate the Inflation Reduction Act, taking the lead in the pharma industry's opposition to the landmark drug pricing law. The 28-page suit against the US Department of Health and Human Services pulls few punches in its rhetoric, criticizing parts of the law as a sham and closer to extortion than negotiation. The heart of Merck’s legal argument, filed Tuesday morning in the US District Court for the District of Columbia, claims the bill violates the First and Fifth Amendments. "By coercing Merck to provide its drug products at government-set prices, the program takes property for public use without just compensation," Merck said in a statement accompanying the suit. "Merck intends to litigate this matter all the way to the US Supreme Court if necessary." The IRA was signed into law last August, giving Medicare the power to negotiate prices for a limited number of drugs. The law was a win for President Joe Biden and Democrats, who have attempted to bring forward a drug price law for years, and a rare defeat for pharma on Capitol Hill. The HHS is set to select the first 10 drugs in September — and Merck said in the lawsuit that it expects its diabetes blockbuster Januvia, which sold $4.5 billion last year, will be on the list. A drugmaker lawsuit is far from unexpected — the only question has been which company would actually move against the law. Industry executives and trade groups have decried the bill even before it became law, saying it’s closer to price-setting than negotiations, and hinted that legal challenges were being considered. |
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Rob Davis, Merck CEO (The Galien Foundation) |
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by Jaimy Lee, Nicole DeFeudis, Andrew Dunn
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Merck may be the first company to sue and try to stop the Inflation Reduction Act. But it almost certainly won’t be the only one. The lawsuit likely aims to stop the US from publishing the first list of drugs that would be subject to pricing negotiation by Medicare, with Merck alleging that the IRA violates the First and Fifth Amendments by forcing the company to give discounts without the option of walking away, according to the suit, which was filed Tuesday in the US District Court for the District of Columbia. Merck, which is largely viewed as a staid corporate leader, described the legislation as “political Kabuki theater” in the lawsuit. However, HHS said it plans to defend the drug price negotiation law. “The law is on our side,” HHS Secretary Xavier Becerra said in a statement. Merck is almost certain to have allies quickly join its side. Just hours after the lawsuit was filed, Biogen CEO Chris Viehbacher said at the BIO meeting in Boston that he wasn't surprised by the suit and agreed with its description of the IRA as “extortion." Viehbacher, the former CEO of French pharma Sanofi, said the law goes far beyond the rules in less pharma-friendly Europe. "The governments in Europe never put anything anywhere near the draconian measures that are in the IRA," he said. Viehbacher said he wouldn't be surprised if more companies file lawsuits, and that Biogen is looking at that option. PhRMA, the industry lobbying group, also appeared to raise the specter of additional lawsuits. |
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by Tyler Patchen
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The FDA is hoping its latest solution will stave off the continued shortage of cisplatin, a key drug used in treating several types of cancer. Beginning tomorrow, orders can be placed for cisplatin shipments from China-based Qilu Pharmaceutical Co., which worked in coordination with the FDA and generic drugmaker Apotex to try to help with the shortage. FDA Commissioner Robert Califf said on Friday that the agency began the process to import certain “foreign-approved versions” of cisplatin from FDA-registered facilities. According to a document, Qilu has started the “temporary importation” of cisplatin into the US even though the injection from Qilu is marketed and manufactured in China and is not approved by the FDA. But Califf was adamant in his post that in situations requiring importation, the agency will “carefully assess product quality” and require the manufacturers to ensure the products are safe. https://twitter.com/DrCaliff However, no details as to the physical amounts or what steps Qilu is taking to comply with the FDA were immediately available. Endpoints News did reach out to Qilu but did not receive a response by press time. The cisplatin shortage has been weighing on the FDA. Last week, Richard Pazdur, director of the FDA’s Oncology Center of Excellence, told The Cancer Letter that to restore the cisplatin supply the FDA is offering assistance to manufacturers to boost production and look at the temporary importation. The importation of the drug is being met as a positive step by experts, but further steps do need to be taken to resolve the situation. |
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Sen. Ron Wyden (D-OR) (Francis Chung/E News/POLITICO via AP Images) |
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by Tyler Patchen
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Sen. Ron Wyden (D-OR) is putting pressure on regulators to address an ongoing shortage of amphetamine mixed salts, a generic form of Adderall that treats ADHD. The senator said in letters last week to DEA Administrator Anne Milgram and FDA Commissioner Robert Califf that he is "deeply disappointed on behalf of the Oregonians I represent" over the agencies' response to the shortage. “While I appreciate that your staff followed up with more information on the role the Center for Drug Evaluation and Research (CDER) plays in preventing and mitigating drug shortages, it falls short of the statement and actions needed. Specifically, the process is muddy and obscure as to how generic manufacturers are navigating the process to request a quota increase, and the fact that your agency does not seek out or report regional data is a grave concern,” the letter said. Wyden added that he continues to support action that would establish requirements for manufacturers to report sustained increases in demand, but until that action is taken, he believes "the agency has a responsibility to provide clear guidance and outreach to manufacturers of these essential medications that are now difficult to access." “The agency should request updates from manufacturers on their ability to meet consumer demand, and inform the public accordingly,” the letter said. "You have authority and opportunity to move us toward solutions to these significant drug shortages.” |
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by Tyler Patchen
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Foghorn Therapeutics, a gene-focused biotech, has been given the all-clear to proceed with a trial assessing its therapy aimed at treating cancers found in the blood and bone marrow. Foghorn said Monday that the FDA lifted the clinical hold on its Phase I monotherapy dose escalation study of FHD-286 to treat acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Last August, the company attributed the FDA's clinical hold to suspected cases of fatal differentiation syndrome, which was believed to be related to FHD-286. Differentiation syndrome is a side effect that is associated with treatments for AML and MDS; it can cause trouble breathing, low blood pressure, and kidney failure and it can be life-threatening, as well, if it's not treated. However, the FDA lifted the hold last week after Foghorn changed some of the protocols in the trial. The company now plans to start a Phase I study of FHD-286 in combination with the chemotherapies decitabine or low-dose cytarabine (LDAC) in AML patients who have relapsed in the third quarter of this year. “Clinical data suggest FHD-286 is a potent, broad-based differentiation therapeutic, and we believe it has significant combination potential as a treatment in AML,” Foghorn CEO Adrian Gottschalk said in a release. Foghorn's stock price FHTX was up about 11% on Monday morning. |
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by Lei Lei Wu
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The FDA has lifted a partial clinical hold on Molecular Templates’ early-stage trial for a multiple myeloma drug, the biotech company announced Thursday morning. Regulators had put the trial on partial hold in early April, pausing patient enrollment, following two adverse heart-related events in patients who received the highest dose of Molecular Templates’ treatment MT-0169 last year. One patient had asymptomatic grade 2 myocarditis, or heart muscle inflammation, while the other had a grade 3 cardiomyopathy. Both recovered within two months. Molecular Templates’ multiple myeloma drug is an engineered toxin body, which features a targeting antibody domain fused to an engineered bacterial protein that induces cell death. The drug targets CD38, which is highly expressed in multiple myeloma cells, in hopes of killing those cells. The Austin, TX-based biotech said it's focusing on studying the drug candidate in extramedullary myeloma, an aggressive form of the disease in which tumors form outside the bone marrow. Just before the clinical hold, Molecular Templates laid off more than 100 workers — approximately half its staff — and cut back on research work to focus on three clinical programs including the multiple myeloma one. |
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John Carroll
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Worldwide made. Thanks for reading.
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