Day: 28 1 月, 2025

TOKYO and CAMBRIDGE, Mass., Jan 28, 2025 - (JCN Newswire via SeaPRwire.com) - Eisai Co., Ltd. and Biogen Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved the Supplemental Biologics License Application (sBLA) for once every four weeks lecanemab-irmb (U.S. brand name: LEQEMBI®) intravenous (IV) maintenance dosing. LEQEMBI is indicated for the treatment of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) or mild dementia stage of disease (collectively referred to as early AD) in the U.S. After 18 months of once every two weeks initiation phase, a transition to the maintenance dosing regimen of 10 mg/kg once every four weeks may be considered or the regimen of 10 mg/kg once every two weeks may be continued.The sBLA is based on modeling of observed data from the Phase 2 study (Study 201) and its long-term extension (LTE) as well as the Clarity AD study (Study 301) and its LTE study. Modeling simulations predict that transitioning to once every four weeks maintenance dosing after 18 months of once every two weeks treatment will maintain clinical and biomarker benefits of therapy. AD is a progressive, relentless disease caused by a continuous underlying neurotoxic process that begins before and continues after plaque removal.1,2,3 Only LEQEMBI works to fight AD in two ways: continuously clearing protofibrils and rapidly clearing plaque. This is important because with continuous administration, LEQEMBI clears highly toxic protofibrils* which can continue to cause neuronal injury even after the amyloid-beta (Aβ) plaque has been cleared from the brain.Importance of Ongoing TreatmentData from the off-treatment period between the Study 201 (Phase 2) core study and LTE showed that discontinuation of treatment is associated with reaccumulation of amyloid PET and plasma and CSF biomarkers, and reversion to placebo rate of clinical decline.4For maintenance treatment, once every four weeks dosing regimen may be easier than once every two weeks dosing for patients and care partners to continue treatment for early AD.Ongoing treatment can slow disease progression and prolong the benefit of therapy,4 with the goal of helping patients maintain who they are for longer.In the Clarity AD core study (18 months), the mean change from baseline between the once every two weeks lecanemab treated group and the placebo group was -0.45 (P1 cm, some of which have been fatal, have been observed with this class of medications. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy to a patient being treated with LEQEMBI.Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (~15% of patients with AD) treated with this class of medications have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed, they can still be treated with LEQEMBI; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA.Consider the benefit of LEQEMBI for the treatment of AD and the potential risk of serious ARIA events when deciding to initiate treatment with LEQEMBI.CONTRAINDICATIONLEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI. Reactions have included angioedema and anaphylaxis.WARNINGS AND PRECAUTIONSAMYLOID-RELATED IMAGING ABNORMALITIESMedications in this class, including LEQEMBI, can cause ARIA-E, which can be observed on MRI as brain edema or sulcal effusions, and ARIA-H, which includes microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD, particularly in patients with MRI findings suggestive of cerebral amyloid angiopathy (CAA), such as pretreatment microhemorrhage or superficial siderosis. ARIA-H generally occurs with ARIA-E. Reported ARIA symptoms may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms usually resolve over time.Incidence of ARIASymptomatic ARIA occurred in 3% and serious ARIA symptoms in 0.7% with LEQEMBI. Clinical ARIA symptoms resolved in 79% of patients during the period of observation. ARIA, including asymptomatic radiographic events, was observed: LEQEMBI, 21%; placebo, 9%. ARIA-E was observed: LEQEMBI, 13%; placebo, 2%. ARIA-H was observed: LEQEMBI, 17%; placebo, 9%. No increase in isolated ARIA-H was observed for LEQEMBI vs placebo.Incidence of ICHICH >1 cm in diameter was reported in 0.7% with LEQEMBI vs 0.1% with placebo. Fatal events of ICH in patients taking LEQEMBI have been observed.Risk Factors of ARIA and ICHApoE ε4 Carrier StatusOf the patients taking LEQEMBI, 16% were ApoE ε4 homozygotes, 53% were heterozygotes, and 31% were noncarriers. With LEQEMBI, ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes vs 2% of heterozygotes and 1% of noncarriers. Serious ARIA events occurred in 3% of ApoE ε4 homozygotes and in ~1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.Radiographic Findings of CAANeuroimaging findings that may indicate CAA include evidence of prior ICH, cerebral microhemorrhage, and cortical superficial siderosis. CAA has an increased risk for ICH. The presence of an ApoE ε4 allele is also associated with CAA.The baseline presence of at least 2 microhemorrhages or the presence of at least 1 area of superficial siderosis on MRI, which may be suggestive of CAA, have been identified as risk factors for ARIA. Patients were excluded from Clarity AD for the presence of >4 microhemorrhages and additional findings suggestive of CAA (prior cerebral hemorrhage >1 cm in greatest diameter, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of ICH.Concomitant Antithrombotic or Thrombolytic MedicationIn Clarity AD, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. Most exposures were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of ICH: 0.9% in patients taking LEQEMBI with a concomitant antithrombotic medication vs 0.6% with no antithrombotic and 2.5% in patients taking LEQEMBI with an anticoagulant alone or with antiplatelet medication such as aspirin vs none in patients receiving placebo.Fatal cerebral hemorrhage has occurred in 1 patient taking an anti-amyloid monoclonal antibody in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent.Additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with LEQEMBI.Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for ICH and, in particular, patients who need to be on anticoagulant therapy or patients with findings on MRI that are suggestive of CAA.Radiographic Severity With LEQEMBIMost ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time, and patients can have >1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in 4%, moderate in 7%, and severe in 1% of patients. Resolution on MRI occurred in 52% of ARIA-E patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. Maximum radiographic severity of ARIA-H microhemorrhage with LEQEMBI was mild in 9%, moderate in 2%, and severe in 3% of patients; superficial siderosis was mild in 4%, moderate in 1%, and severe in 0.4% of patients. With LEQEMBI, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes (5%) vs heterozygotes (0.4%) or noncarriers (0%). With LEQEMBI, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes (13.5%) vs heterozygotes (2.1%) or noncarriers (1.1%).Monitoring and Dose Management GuidelinesBaseline brain MRI and periodic monitoring with MRI are recommended. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment. Depending on ARIA-E and ARIA-H clinical symptoms and radiographic severity, use clinical judgment when considering whether to continue dosing or to temporarily or permanently discontinue LEQEMBI. If a patient experiences ARIA symptoms, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.HYPERSENSITIVITY REACTIONSHypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred with LEQEMBI. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy. INFUSION-RELATED REACTIONS (IRRs)IRRs were observed—LEQEMBI: 26%; placebo: 7%—and most cases with LEQEMBI (75%) occurred with the first infusion. IRRs were mostly mild (69%) or moderate (28%). Symptoms included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.In the event of an IRR, the infusion rate may be reduced or discontinued, and appropriate therapy initiated as clinically indicated. Consider prophylactic treatment prior to future infusions with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids.ADVERSE REACTIONSThe most common adverse reactions reported in ≥5% with LEQEMBI and ≥2% higher than placebo were IRRs (LEQEMBI: 26%; placebo: 7%), ARIA-H (LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache (LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system (LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting (LEQEMBI: 6%; placebo: 4%).Please see full Prescribing Informationincluding Boxed WARNING.About lecanemab (LEQEMBI®)Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ). Lecanemab is approved in the U.S.,7 Japan,8 China,9 South Korea,10 Hong Kong,11 Israel,12 the United Arab Emirates,13 the United Kingdom,14 Mexico,15 and Macau. In November 2024, the treatment received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval. Eisai has submitted applications for approval of lecanemab in 17 countries and regions.LEQEMBI’s approvals in these countries was based on Phase 3 data from Eisai’s, global Clarity AD clinical trial, in which it met its primary endpoint and all key secondary endpoints with statistically significant results. The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with lecanemab reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo.16,17 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P

TOKYO, Jan 27, 2025 - (JCN Newswire via SeaPRwire.com) - Sébastien Ogier has claimed a record-extending 10th victory on the legendary Rallye Monte-Carlo as TOYOTA GAZOO Racing World Rally Team scored a one-two finish to launch its 2025 FIA World Rally Championship campaign with a maximum points haul.The victory is Ogier’s third Rallye Monte-Carlo win with TGR-WRT and his second with co-driver Vincent Landais, and brings Toyota’s all-time record on the event to six wins.As usual the rally brought a wide range of changeable conditions during the weekend, with dry asphalt stages in the mountains of the French Alps also featuring sections of ice as well as plenty of mud and gravel being dragged onto the road. It provided a challenging first event for the teams and drivers with the revised technical package for 2025, with the top class of Rally1 cars no longer featuring hybrid units and also running on Hankook tyres for the first time.Despite these challenges, the battle for victory remained tight throughout the weekend and went down to the very last stage across the iconic Col de Turini on Sunday afternoon. Ogier had eked out a lead of 20.3 seconds over Evans going into the final day, with the Hyundai pair of Adrien Fourmaux and Ott Tänak also close behind, but an early start combined with cold and wet conditions made for a difficult last tyre choice.Ogier and Evans both took a package of four studded winter tyres plus two supersoft slick tyres, which paid off in the icy first stage prior to sunrise. With the four studded tyres fitted they were around 20s quicker than Fourmaux, but that advantage swung the other way on a drier second stage, where Fourmaux could fit his four slicks and close back to within 4s of Evans and 22.2s of Ogier.The rally-ending Power Stage featured a true mix of conditions, with a largely dry ascent and descent but with some ice atop the famous Col. In the end, all of the top three drivers opted for a mix of slick and studded tyres and it was Ogier who set the best time, just 0.215s quicker than Evans – who ran wide and brushed a bank on the rapid descent to the finish.Ogier’s win is also his 15th for TGR-WRT, drawing him level with team-mate Kalle Rovanperä and their fellow two-time champion Carlos Sainz as the drivers who have achieved the most WRC victories for Toyota.Evans and co-driver Scott Martin start their season strongly, also topping the Super Sunday classification to earn five extra bonus points. 1.1s in front of Rovanperä and 1.8s in front of Ogier.With a different tyre strategy, Rovanperä and Jonne Halttunen were consistent across all conditions on the final day and beat Ott Tänak to fourth overall, securing a solid haul of 18 points from a challenging weekend.Takamoto Katsuta and Sami Pajari built their confidence and pace through the rally. Katsuta won a stage and was third-quickest across Saturday, while Pajari gathered valuable experience on his first Rallye Monte-Carlo in Rally1 machinery. Starting the final day sixth and seventh, both would unfortunately slide off the road in Sunday’s first stage.Quotes:Akio Toyoda (TGR-WRT Chairman)We were able to kick off the 2025 season with Seb's memorable 10th victory in Monte Carlo. Up until 2019, Seb had a streak of six consecutive wins in Monte Carlo with various teams. Since joining Toyota in 2020, he has alternated between 2nd and 1st place every other year. Given this pattern, I was certain that he would win this year. Seb, congratulations on your 10th win in Monte Carlo! I think it's time for you to break that pattern and win again next year!Last season was incredibly enjoyable, as we battled with Hyundai all the way to the final stage of the final round. However, that was just how I felt as a rally fan. As a team member, there were many moments that were quite tough throughout the season. This year, I want to make it a season that we can enjoy from the bottom of our hearts also as team members. And I want to experience that feeling again at Rally Japan! I believe Jari-Matti, Juha, all the drivers, all the co-drivers, and everyone in the team will make it happen! And just so you know, this year's Rally Japan is not the final event...Quotes:Jari-Matti Latvala (Team Principal)“I’m really delighted. We could not really have had a better start to the season than this: we got the maximum 60 points as a team, a one-two-four overall and the 10th victory for Sébastien Ogier on Rallye Monte-Carlo, which is a truly amazing and unique achievement. The conditions were very difficult until the end and the tyre choice was stressful this morning because the road was freezing after the route-note crews had passed through. Unfortunately Sami and Taka went off, and perhaps I should have pushed them to take a safer choice, but this rally was all about the experience for them. With our other drivers it worked out well in the end, so thank you to them. At the same time it was a very entertaining rally and I think we have an exciting season ahead.”Elfyn Evans (Driver car 33)“This was a typical Rallye Monte-Carlo, a bit more extreme than in recent years and it was a properly challenging weekend. I’m very happy to be here at the end with a decent haul of points. Today started off with some very tricky conditions, we made a change at the last moment to take four studded tyres and I wasn’t sure it was the right call. In the end it seems there wasn’t a lot between the two choices and we had a pretty thrilling Power Stage to finish: we had a close moment a few corners from the end but thankfully we managed to get away with it.”Kalle Rovanperä (Driver car 69)“Rallye Monte-Carlo is always tough and it was especially so this year. For me personally it was a pretty difficult weekend. We didn’t have the result that we wanted or the pace that we wanted but we have to be happy at the end to have got some pretty good points. Today was not a bad day for us: we just tried our best, kept consistent and it paid off. A big thanks to the team, now let’s see what we can do in Sweden.”Sébastien Ogier (Driver car 17)“It’s amazing to win this rally for the 10th time: it makes me incredibly happy and proud. This rally is the one that gave me the dream to be a rally driver, so if I could pick only one to win in a season, it would always be this one. This year it’s been a huge fight up until the very last stage. We had changing conditions, difficult tyre decisions and pressure right until the end so I’m glad we managed to keep it under control. We definitely had some moments but to win this rally I think you always need a bit of luck too. It’s a perfect start to the year for the team so we couldn’t ask for anything more.”Takamoto Katsuta (Driver car 18)“This morning in the first stage we knew that the conditions could be quite tricky, but we came to one right-hand corner that was frosty where we didn’t have that information in our pacenotes. We were quite slow going into the corner, but the car went wide and got stuck in a small ditch which we couldn’t get out of. Until then it had been quite a good rally, especially Saturday when the pace was good. It’s a pity but I just need to refocus on the next rally in Sweden and try to do a good job for the team there.”Sami Pajari (Driver car 5)“The approach for today was the same as before and we were not planning to push particularly hard. There was just one surprisingly icy braking point which just caught us out. It was an unfortunate end to our rally, as it been going according to plan until then. On Saturday especially we saw that the times were getting better and the feeling was getting better and the confidence was rising. Everything felt under control so it’s a pity to end the rally like this, but we will try to learn from what happened and look forward to Sweden.”PROVISIONAL FINAL CLASSIFICATION, RALLYE MONTE-CARLO1 Sébastien Ogier/Vincent Landais (Toyota GR YARIS Rally1) 3h19m06.1s2 Elfyn Evans/Scott Martin (Toyota GR YARIS Rally1) +18.5s3 Adrien Fourmaux/Alexandre Coria (Hyundai i20 N Rally1) +26.0s4 Kalle Rovanperä/Jonne Halttunen (Toyota GR YARIS Rally1) +54.3s5 Ott Tänak/Martin Järveoja (Hyundai i20 N Rally1) +59.0s6 Thierry Neuville/Martijn Wydaeghe (Hyundai i20 N Rally1) +5m44.2s7 Josh McErlean/Eoin Treacy (Ford Puma Rally1) +10m15.1s8 Yohan Rossel/Arnaud Dunand (Citroën C3 Rally2) +10m26.8s9 Nikolay Gryazin/Konstantin Aleksandrov (Škoda Fabia RS Rally2) +11m40.7s10 Eric Camilli/Thibault de la Haye (Hyundai i20 N Rally2) +13m14.6sRetired Takamoto Katsuta/Aaron Johnston (Toyota GR YARIS Rally1)Retired Sami Pajari/Marko Salminen (Toyota GR YARIS Rally1)(Results as of 14:30 on Sunday, for the latest results please visit www.wrc.com)2025 FIA World Rally Championship for drivers after round 1:1 Sébastien Ogier 33 points2 Elfyn Evans 263 Adrien Fourmaux 204 Kalle Rovanperä 185 Ott Tänak 116 Thierry Neuville 97 Josh McErlean 68 Yohan Rossel 49 Nikolay Gryazin 210 Eric Camilli 12025 FIA World Rally Championship for manufacturers after round 1:1 TOYOTA GAZOO Racing World Rally Team 60 points2 Hyundai Shell Mobis World Rally Team 363 M-Sport Ford World Rally Team 11What's next?Rally Sweden (February 13-16) is the only full winter event of the season held on snow and ice. Metal studs inserted into the tyres bite into the surface to provide grip and allow for some of the highest speeds of the year. Copyright 2025 JCN Newswire via SeaPRwire.com.