Amnesia, Anterograde

Eisai and Biogen’s Leqembi received accelerated approval from the US Food and Drug Administration (FDA) in January, which was converted into full approval earlier this month. Image Credit: Alessandro Zappalorto / Shutterstock The European Medicines Agency (EMA) has halted Eisai and Biogen ’s expansion plan to launch its Alzheimer’s disease therapy Leqembi (lecanemab) in Europe after its drug review committee recommended against the therapy’s approval. The Committee for Medicinal Products for Human Use (CHMP) stated that Leqembi’s positive effect on delaying cognitive decline was “not large enough” to counterbalance the associated risk of serious adverse events. Eisai was quick to add that the company plans to re-examine the CHMP opinion. The committee was particularly concerned with the risk of developing amyloid-related imaging abnormalities (ARIA). These are observed exclusively on MRI and can signify oedema, effusion and /or haemorrhage. CHMP noted that “although most cases of ARIA in the main study were not serious and did not involve symptoms, some patients had serious events, including large bleeds in the brain which required hospitalisation.” The risk of ARIA was increased in patients with ApoE4 gene, the presence of one or more copies of the gene predisposes an individual to develop Alzheimer’s disease. The committee also pointed out that the difference in the improvement of cognitive decline , measured using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score, between the Leqembi and placebo arms was “small”. Adding that “the seriousness of this side effect should be considered in the context of the small effect seen with [Leqembi].” See Also: Mankind Pharma acquires Bharat Serums and Vaccines for $1.6bn AC Immune wins FDA fast track for Alzheimer’s vaccine Leqembi works by targeting the buildup of amyloid plaques in the brain, a hallmark of Alzheimer’s disease and a suggested cause of memory and cognition impairment. It received accelerated approval from the US Food and Drug Administration (FDA) in January, which was converted into full approval earlier this month. Leqembi is an important  drug for Biogen, which is codeveloping the drug with Eisai, especially after the former discontinued its other controversial Alzheimer’s treatment Aduhelm (aducanumab-avwa), in January. A GlobalData analysis forecasts Leqembi to generate over $6.1bn in sales by 2030. GlobalData is the parent company of Pharmaceutical Technology . Eisai and Biogen have also filled a supplemental biologics application (sBLA) with the US FDA for monthly Leqembi IV maintenance dosing for the treatment of patients with Alzheimer’s disease, with the Prescription Drug User Fee Act (PDUFA) action date being set for 25 January 2025.

SARASOTA, Fla., June 27, 2024 (GLOBE NEWSWIRE) -- Oragenics, Inc. (NYSE American: OGEN), a company focused on developing unique, intranasal pharmaceuticals for the treatment of neurological disorders, today announced it has completed a prototype of its automated intranasal device for use in concussed patients who are initially confused, dazed or unconscious in the acute phase of injury. Oragenics’ lead drug candidate, ONP-002, is a new chemical entity (NCE) designed to target the brain through delivery into the nasal cavity and onward to the brain. A Phase II study is being designed to analyze the effectiveness of ONP-002 on blood biomarkers and patient-reported outcomes of concussed patients. Loss of consciousness along with acute memory impairment are linked to prolonged post-concussion symptoms and poor clinical outcomes. Oragenics’ breath-propelled device requires the patient to administer ONP-002 into the nose. Concussed patients with an acute altered mental state may not be capable of following these instructions. Oragenics intends to use its breath-propelled device in the planned Phase II trial, which calls for multiple days of treatment. However, for those patients who have a loss of consciousness or altered mental status early on, the current automated prototype is being developed for their initial treatment by medical staff during the period in which they may struggle to follow directions for blowing. “We are excited about this new automated technology as it allows us to treat the full range of concussive injuries. Both devices offer advantages and can deliver our nanoparticle powder. Given the early mental alterations many concussed patients experience, we aim to provide them the best drug delivery route to improve their clinical outcomes,” stated Michael Redmond, President at Oragenics. Approximately 10% of concussed patients lose consciousness, while many others experience an immediate altered mental state, with short-term memory loss and confusion. Both loss of consciousness and acute memory impairment are linked to prolonged post-concussion symptoms and poor clinical outcomes. Concussion is an unmet medical need. There are an estimated 69 million concussions annually reported worldwide. Common causes of concussion include falls, motor vehicle accidents, and contact sports. Other neurological disorders, including Alzheimer’s Disease, Parkinson’s Disease, and Chronic Traumatic Encephalopathy (CTE), have been linked to concussion. Post-concussion symptomology is linked to long-term disability and occurs in as high as 20% of concussed patients. About Oragenics Forward-Looking Statements This communication contains “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including without limitation statements regarding the ability of the Company to timely and successfully undertake Phase II clinical trial using its novel drug-device combination for the treatment of mild Traumatic Brain Injury. These forward-looking statements are based on management’s beliefs and assumptions and information currently available. The words "believe," "expect," "anticipate," "intend," "estimate," "project" and similar expressions that do not relate solely to historical matters identify forward-looking statements. Investors should be cautious in relying on forward-looking statements because they are subject to a variety of risks, uncertainties, and other factors that could cause actual results to differ materially from those expressed in any such forward-looking statements. These factors include, but are not limited to: the Company’s ability to advance the development of its product candidates, including the neurology assets, under the timelines and in accord with the milestones it projects; the Company’s ability to raise capital and obtain funding, non-dilutive or otherwise, for the development of its product candidates; the regulatory application process, research and development stages, and future clinical data and analysis relating to its product candidates, including any meetings, decisions by regulatory authorities, such as the FDA and investigational review boards, whether favorable or unfavorable; the Company’s ability to obtain, maintain and enforce necessary patent and other intellectual property protection; the nature of competition and development relating to concussion treatments; the Company’s expectations as to the outcome of preclinical studies and clinical trials and the potential benefits, activity, effectiveness and safety of its product candidates including as to administration, transmission, manufacturing, storage and distribution; and general economic and market conditions and risks, as well as other uncertainties described in our filings with the U.S. Securities and Exchange Commission. All information set forth is as of the date hereof unless otherwise indicated. You should consider these factors in evaluating the forward-looking statements included and not place undue reliance on such statements. We do not assume any obligation to publicly provide revisions or updates to any forward-looking statements, whether as a result of new information, future developments or otherwise, should circumstances change, except as otherwise required by law. Oragenics, Inc. Janet Huffman, Chief Financial Officer 813-286-7900 jhuffman@oragenics.com Investor Relations: Rich Cockrell CG Capital 404-736-3838 ogen@cg.capital

Leqembi (lecanemab-irmb), approved in the US, Japan, and China, is currently administered intravenously. Credit: Shutterstock/Tavarius. Eisai has initiated a rolling submission to the US Food and Drug Administration (FDA) for approval of a more convenient version of its Alzheimer’s disease treatment Leqembi (lecanemab-irmb). The biologics licence application (BLA) is for a subcutaneous autoinjector version of the drug that is currently infused. A rolling submission allows a company to submit sections of an application as each one is completed, rather than waiting for the entire application to be finished. Eisai became eligible to apply via this pathway after winning fast track designation from the FDA, as per a 14 May press release. Developed in partnership with Biogen , an intravenous (IV) form of Leqembi was approved in the US in July 2023. While the antibody-based therapy has made waves in the neurodegenerative disease space, its uptake has been hampered due to treatment logistics. Patients first require extensive imaging scans before taking the medication and often must travel to specialist sites for the infusion. Eisai said in a Q3 FY 2023 earnings call that a total of 2,000 patients had been administered the treatment as of 26 January 2024. The company had set a target of 10,000 treated patients by the end of March. See Also: FDA approves Bristol Myers Squibb’s Breyanzi for follicular lymphoma Risk adjusted net present value: What is the current valuation of Eisai’s Etalanetug? Eisai and Biogen say the new autoinjector could be used to administer Leqembi at home and in medical facilities. If approved, the new formulation would be used as a 360mg dose for weekly maintenance dosing following a biweekly IV initiation phase. The two companies added that administering the under-the-skin injection requires less time compared to the original IV version. Supporting the BLA is data from the Clarity AD (Study 301) open-label extension, along with modelling of observed data. Eisai and Biogen reported data at last year’s Clinical Trials on Alzheimer’s Disease annual meeting that demonstrated subcutaneous Leqembi worked just as well as the IV counterpart. Subcutaneous Leqembi cleared 14% more amyloid plaque in the brain in 71 patients compared to the original version. The drug works by targeting the buildup of amyloid plaques in the brain – a hallmark of Alzheimer’s disease and what is suggested as a cause of memory and cognition impairment. The company was initially supposed to file this rolling BLA in March 2024, but the FDA requested more immunogenicity data, leading to a delay in filing . However, Eisai and Biogen’s major competitor, Eli Lilly, is also facing delays with its Alzheimer’s therapy donanemab. It means that Eisai and Biogen currently enjoy market dominance in the Alzheimer’s disease treatment space. Biogen recently redirected all resources to Leqembi after cutting ties with its other Alzheimer’s asset Aduhelm (aducanumab-avwa). Leqembi, which is also approved in Japan and China, is predicted to bring in global sales of $372m in 2024 according to GlobalData’s Pharma Intelligence Centre. The forecast for the drug is impressive, estimated to reel in $7.3bn by 2030. GlobalData is the parent company of Pharmaceutical Technology . Pricing could yet remain a hurdle for the drug’s long-term prospects. A year’s supply of the drug comes with a price tag of $26,600, and while Medicare said last year it would cover 80% of the drug’s $26,500 yearly price tag for eligible patients, a study has suggested this could cost the agency up to $5bn a year, demonstrating the possible healthcare burden.