Harbor Diversified, Inc.

Courtesy of John Tlumacki/The Boston Globe via Getty Biogen experienced a turbulent end to a turbulent 2022. Last week, two documents came to light: one the results of a congressional investigation into the approval of its Alzheimer’s drug Aduhelm (aducanumab), the second a revised informed consent form calling into question the safety of lecanemab, which could receive accelerated approval this week. On Friday, Science revealed Biogen’s development partner Eisai updated the consent form for the Phase III Clarity AD trial warning participants that combining lecanemab with blood clot medications could lead to fatal brain hemorrhages. The revision was made in a July 14 version of the consent form, Science reported. In part, Eisai wrote the “risk is estimated to be more than 1 in 100 people, but less than 5 in 100 people.” This follows reports of two trial participant deaths allegedly associated with lecanemab. In a presentation at the 2022 Clinical Trials on Alzheimer's Disease (CTAD) conference, Marwan Sabbagh, M.D., a behavioral neurologist at the Barrow Neurological Institute, said the two fatalities were associated with cerebral microhemorrhages in the open-label extension phase of the study. Libby Holman, senior director of product communications at Eisai U.S. referred BioSpace to a statement that reads in part, "Eisai promptly communicates important safety information to the DSMBs, regulatory agencies, sites, investigators and patients through a variety of appropriate mechanisms, including... Informed Consent Form (ICF) revisions." The company additionally expressed confidence that the informed consents used in its studies accurately describe the known risks associated with lecanemab. The PDUFA date for lecanemab is Friday, January 6. If Biogen and Eisai do receive accelerated approval this week, the price point for the antibody must be set at lower than $20,600 a year to be cost-effective, according to the Institute for Clinical and Economic Review (ICER). The Watchdog further calculated the drug’s clinical benefits at between $8,500 and $20,600 per year. In September, the partners announced lecanemab reduced clinical decline by 27% compared to placebo after 18 months. The initial price for Aduhelm, which in June 2021 became the first drug approved to treat Alzheimer’s in 18 years, was $56,000 per patient, per year. Following a spate of controversy and insurers refusing to cover the drug, Biogen slashed the price to $28,200 in December 2021. At the time of Aduhelm’s approval, ICER recommended a price point of between $2500 and $8300 per patient per year, alleging “insufficient efficacy”. Results from the Phase III Emerge and Engage trials were mixed, and Biogen and Eisai initially made the decision to discontinue both trials due to futility. Congressional Investigation Reveals “Atypical Processes” Almost immediately after the green light, the U.S. House of Representatives launched an investigation into the regulatory review and approval, pricing and marketing of Aduhelm. The final report, prepared by the Committees on Oversight and Reform, and Energy and Commerce, was published Thursday. The report points to a joint briefing document prepared and presented by Biogen and the FDA to the regulator’s Peripheral and Central Nervous Systems Drugs Advisory Committee in November 2020 – a joint process that had previously been used only for cancer drugs “under circumstances of broad consensus”. The adcomm overwhelmingly voted against traditional approval for Aduhelm. While the report ultimately concluded the interactions between the FDA and Biogen prior to the PCNS adcomm were appropriate, it highlighted “atypical processes.” Among these, the investigators found: Documents showing Biogen and the FDA engaged in at least 115 meetings, calls and substantive email exchanges over a 12-month period beginning in July 2019. According to the report, the regulator’s own internal review of the approval process found the extent of collaboration was “atypical” and “exceeded the norm in some respects.” The FDA and Biogen “inappropriately collaborated on a joint briefing document for the PCNS advisory committee that did not adequately represent differing views within FDA.” “Biogen set an unjustifiably high price for Aduhelm to ‘Make History’ for the company despite the impact on patients and the Medicare program.” The report specifically highlighted a September 2020 presentation to Biogen’s board where the company stated its ambition was to make history and “establish Aduhelm as one of the top pharmaceutical launches of all time.” On this last point, only time – possibly three days – will tell if Biogen heeds the lessons provided it by insurers and Medicare itself – on the pricing of lecanemab.

The total funding could reach €17.5 million ($18.6 million). Paris-based Carmat develops a total artificial heart. It designed the platform to provide a therapeutic alternative for those suffering from end-stage biventricular heart failure. EIC Accelerator funds European companies aiming to bring innovations to market. The council selected Carmat and its Aeson artificial heart, recognizing it as a “high-quality medical innovation,” according to a news release. As a result of the selection, Carmat received the maximum possible funding available. It picked up a non-dilutive grant of €2.5 million ($2.7 million) to support the industrialization of Aeson. Additionally, Carmat received an optional equity financing of €15 million ($15.9 million). This funding, from the European Innovation Council Fund, supports marketing efforts for Aeson. “We are proud and grateful to have been awarded within this prestigious program,” said Stéphane Piat, Carmat CEO. “The EIC’s decision confirms the very high quality and strong potential of our innovation and gives us access to substantial funding to support our development. I would like to thank all the Carmat teams involved in this challenging call for projects, which once again highlights the urgent need for an innovative solution to treat advanced biventricular heart failure.” Carmat’s Aeson artificial heart system includes three parts: an implanted prosthesis, external equipment and a hospital care console. The prosthesis includes two micro pumps that push the actuator fluid to the membranes and generate the systole and diastole. There are two ventricles chambers, with a membrane separating them. One part is for blood, and one is for the actuator flood. The Aeson’s creators made the blood-contacting layer of the membrane out of biocompatible materials.

As debate rages on Capitol Hill over whether to add riders, and which riders to add, to the must-pass FDA user fee legislation, the Congressional Budget Office on Thursday made clear that the Senate version will reduce the federal deficit by about $1.4 billion over the next 10 years. Congress has until the end of September to reauthorize the user fees, which the FDA collects for its review of prescription drugs, generics, biosimilars and medical devices. While there are still major gaps between the Senate and House versions, and health committee ranking member Richard Burr (R-NC) recently introduced a blank version of the bill with no riders, many expect the user fee bills will still get done on time. “I generally still think that a user fee deal will get done before the end of September given that there is broad, bipartisan support for user fees,” Chad Landmon, partner at the law firm Axinn, Veltrop & Harkrider, told Endpoints News via email, adding: In unveiling its deficit-reducing score, CBO points to five key sections of the bill, known as S.4348 or the FDASLA Act of 2022, that will have the biggest impact. First, the non-partisan organization pointed to Section 509, which would authorize the FDA to approve a generic drug application (ANDA) even if the label differs from that of the brand name product when the brand-name label changes within 90 days of the date on which the generic application would otherwise have been eligible for approval. The sponsor of the generic would still be required to update that drug’s label within 60 days of approval, but based on conversations with stakeholders, “CBO expects that the provision would accelerate the availability of lower-priced generic drugs because manufacturers would bring them to market earlier than under current law,” thereby reducing the average prices for those drugs that are paid for by federal health programs. In another move to accelerate the availability of lower-priced drugs, section 511 of FDASLA would allow the FDA to deny a citizen petition if it determines that the petition was submitted with the primary purpose of delaying the approval of an application or if it doesn’t raise valid scientific or regulatory issues. These types of petitions are frequently submitted and used as a delaying tactic when generic drugs are readied for launch. The bill also would require a petition to be submitted within 60 days after the petitioner knew, or reasonably should have known, the information that forms the basis of the petition, thereby pushing companies away from filing these petitions at the last minute. “CBO expects that the new timely-submission requirement and related changes to the dismissal procedures involving civil actions would further enhance the FDA’s ability to expeditiously deny petitions that otherwise would have delayed the marketing approval of generic or biosimilar applications,” the CBO said. Section 512 of the Senate bill, highlighted by CBO, would also accelerate the availability of lower-priced generic drugs, thereby saving the government money, as it would authorize the FDA to disclose qualitative and quantitative information on the inactive ingredients of the brand-name drug in response to a request in a controlled correspondence from a generic drug manufacturer. Another controversial section, section 515, would allow the FDA to approve a subsequent ANDA, under certain conditions, if the first applicant that is eligible for 180 days of generic market exclusivity has not yet begun marketing. While the CBO expects that the provision would accelerate the availability of lower-priced generic drugs because manufacturers would bring them to market earlier than under current law, generic drug experts think this section might do the reverse. Kurt Karst, regulatory counsel at Hyman, Phelps & McNamara, previously told Endpoints that this provision could create new litigation. “This new provision creates an exception to 180-day exclusivity to allow a subsequent applicant to, in a sense, leapfrog into first applicant status almost, and be able to get approved. Notwithstanding a first applicant’s exclusivity subject to a series of five events. Some of them are subject to quite a bit of discretion and anytime the D word comes up, that oftentimes means the L word, right? The lawsuit,” he said during a recent Endpoints panel discussion on the user fee bill. And CBO pointed to Section 605 of the bill, which would reauthorize through 2027 a provision that may slightly increase the deficit over 10 years and allows sponsors of drugs developed from a particular type of molecule called an enantiomer to gain five years of data exclusivity under certain circumstances. Under current law, the CBO says, the “maximum period of data exclusivity would revert to 3 years in 2023. (Data exclusivity begins when a drug is approved by the FDA. During that time, the agency does not accept applications for marketing approval for generic versions of the drug.) Based on historical data, CBO expects that extending market exclusivity for prescription drugs developed from enantiomers would, in some cases, delay the entry of lower-priced generic versions of those drugs.”