Latest news with #HERCULES
Yahoo
21-05-2025
- Science
- Yahoo
University of Michigan researchers develop nation's most powerful laser
GRAND RAPIDS, Mich. (WOOD) — Researchers at the University of Michigan have developed the nation's most powerful laser. The latest design has nearly doubled the peak power of any other laser in the country. The team recently conducted its first successful experiment measured at 2 petawatts — 2 quadrillion watts — which is more than 100 times the global electricity output. Sign up for the News 8 daily newsletter That giant number is matched with something almost equally as small. The power surge is an extremely brief pulse, lasting just 25 quintillionths of a second. The laser, known as the Zettawatt-Equivalent Ultrashort pulse laser system or , is managed by U-M's and supported by the National Science Foundation. Karl Krushelnick, the director of the CUOS, said this latest milestone 'marks the beginning of experiments that move into unexplored territory for American high field science.' Researchers expect the advancements could be applied to several different fields, including medicine, national security and astrophysics. Since it is supported by the NSF, research teams from all over the world can submit experiment proposals for ZEUS. Franklin Dollar, a professor at the University of California-Irvine, is set to lead an experiment at the new power level. 'One of the great things about ZEUS is it's not just one big laser hammer. You can split the light into multiple beams,' he said in a . 'Having a national resource like this, which awards time to users whose experimental concepts are most promising for advancing scientific priorities, is really bringing high-intensity laser science back to the U.S.' University of Michigan launches new $7 billion fundraising campaign CUOS says 'the road to 2 petawatts' has been a long one. The previous laser system, HERCULES, got up to 300 terawatts. ZEUS helped them jump to 1 petawatt. The ZEUS team has already spent more than a year running experiments at that level. ZEUS requires many special pieces to make it work, including a 7-inch sapphire crystal that is infused with titanium atoms. ZEUS project manager Franko Bayer says they are already working on another one that will help them get even stronger. 'The crystal that we're going to get in the summer will get us to 3 petawatts, and it took four-and-a-half years to manufacture,' Bayer said in the blog post. 'The size of the titanium sapphire crystal we have, there are only a few in the world.' Copyright 2025 Nexstar Media, Inc. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
Yahoo
19-05-2025
- Science
- Yahoo
The US test fired its most power laser ever
A laser named after the most powerful god in ancient Greece is living up to its name. According to the University of Michigan, the first official experiment from the Zettawatt-Equivalent Ultrashort pulse laser System (ZEUS) yielded 2 petawatts (2 quadrillion watts) of power. For reference, that's more than 100 times the electricity output across the entire planet—but you'll likely miss it if you blink. The school gym-sized ZEUS is the successor to the university's HERCULES system, which topped out at 300 terawatts. ZEUS relied on a reconfigured target for its debut demonstration, which required firing a laser pulse at a cell containing helium. The subsequent interaction produced plasma as it tore electrons away from the helium atoms, resulting in a mixture of both positive ions and free electrons. The electrons started gaining speed behind the laser pulse in a phenomenon known as wakefield acceleration. Because light moves slower in plasma, the electrons can catch up to the laser beam. Those free electrons also get more time to speed up given the size of the target chamber and thereby hit higher speeds. The recent demonstration is a prelude to the signature ZEUS experiment scheduled for later this year. In that test, the accelerating electrons will also smack into laser pulses coming from the opposite direction. This is where things get (even) more complicated—but to condense it down, the effect makes a 3-petawatt laser appear one million times more powerful, hence the 'zettawatt-equivalent' in ZEUS' name. Accomplishing this and other experimental feats does require some safeguards. ZEUS includes optical devices known as diffraction gratings that stretch out the initial infrared pulse over time. This ensures the initial power doesn't get so intense that it begins tearing apart the air around it. Another goal is to ultimately create beams of electrons with energies similar to those found in particle accelerators hundreds of feet longer than ZEUS at a fraction of both its size and operating costs. At only $16 million to construct, the University of Michigan previously described the machine as a 'bargain.' Years of construction, calibration, and expertise is showcased in an astoundingly short amount of time. ZEUS' 2 petawatt firing lasted just 25 quintillionths of a second. But future experiments will make the most of these moments. 'The fundamental research done at the NSF ZEUS facility has many possible applications, including better imaging methods for soft tissues and advancing the technology used to treat cancer and other diseases,' explained Vyacheslav Lukin, program director in the National Science d Division of Physics, which is responsible for the ZEUS project. Meanwhile, ZEUS experiments could also help researchers explore the dynamics of positron jets that shoot out of black holes, or how gamma ray bursts operate. 'One of the great things about ZEUS is it's not just one big laser hammer, but you can split the light into multiple beams,' said Franklin Dollar, a University of California professor of physics and astronomy who oversaw the 2 petawatt experiment. 'Having a national resource like this, which awards time to users whose experimental concepts are most promising for advancing scientific priorities, is really bringing high-intensity laser science back to the U.S.'
Yahoo
14-04-2025
- Business
- Yahoo
AAN 2025: Sanofi's tolebrutinib likely to be first BTK inhibitor for the treatment of MS
At the American Academy of Neurology (AAN) 2025 Annual Meeting Clinical Trials Plenary Session, Sanofi presented data on tolebrutinib in patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS) from the HERCULES trial and in patients with relapsing multiple sclerosis (RMS) from GEMINI 1 and GEMINI 2. The presentation highlighted tolebrutinib's potential as the first Bruton's tyrosine kinase (BTK) inhibitor to receive regulatory approval for the treatment of progressive MS. During the Clinical Trials Plenary Session, Sanofi announced that tolebrutinib delayed the time to onset of six-month confirmed disability progression (CDP) by 31% compared to placebo in patients with nrSPMS, meeting the primary endpoint of the HERCULES trial. In addition, tolebrutinib met some of its secondary endpoints where it delayed the time to three-month CDP by 24% compared to placebo, and significantly lowered the annualised rate of new or enlarging T2 lesions versus placebo by 38%. While a lower proportion of participants in the tolebrutinib group showed progression in the Timed 25-Foot Walk, tolebrutinib did not differentiate from placebo in the 9-hole peg test. During the Plenary Session, Sanofi also reported that tolebrutinib failed to meet the primary endpoint of reducing annualised relapse rate over teriflunomide in patients with RMS in the GEMINI studies. A pooled analysis of GEMINI 1 and GEMINI 2 for a key secondary endpoint, not controlled for multiplicity, showed that tolebrutinib delayed the time to onset of six-month confirmed disability worsening by 29% versus teriflunomide. But the number of new Gd-enhancing T1 lesions was higher in the tolebrutinib arm and the number of new or enlarging T2 lesions was similar between both treatment arms. The results of the GEMINI trials follow Sanofi's decision, in January 2025, to remove its tolebrutinib RMS programme from its pipeline, focusing on progressive forms of MS only. In addition to development in nrSPMS per the HERCULES trial, there is an ongoing Phase III study to investigate the efficacy of tolebrutinib compared to placebo in delaying disease progression in patients with primary progressive MS (PERSEUS). Tolebrutinib was generally well-tolerated in the HERCULES, GEMINI 1, and GEMINI 2 trials. Liver enzyme elevations, defined by greater than three times the upper limit of normal, were observed in 4.0% of tolebrutinib patients in the HERCULES trial and 5.6% of tolebrutinib patients in the GEMINI studies. However, safety concerns have been previously raised. In June 2022, the US Food and Drug Administration (FDA) placed a partial clinical hold on tolebrutinib due to reported cases of drug-liver induced injury in patients who received the drug during clinical trials. Key opinion leaders (KOLs) previously interviewed by leading data and analytics company GlobalData stated that should tolebrutinib receive approval, it is likely to be accompanied by a boxed warning and risk evaluation and mitigation strategies. The majority of marketed disease-modifying therapies for MS target peripheral inflammation for reducing relapses, but few possess neuroprotective effects and, as such, have insufficient impact on the underlying neurologic deterioration caused by MS. The MS therapeutics market is heavily skewed towards reducing relapses in patients with RMS. KOLs previously interviewed by GlobalData stressed the need for a new product that could prevent disease progression. The gravity of this unmet need is highlighted by the number of BTK inhibitors in clinical development for MS. According to GlobalData's drug database, there are three BTK inhibitors in Phase III development. Tolebrutinib will compete with Genentech/Roche's fenebrutinib, Novartis' remibrutinib, and InnoCare Pharma's orelabrutinib. Last month, Sanofi announced tolebrutinib's US regulatory submission was accepted for priority review, and the target action date for the FDA decision for tolebrutinib is 28 September 2025. If approved, tolebrutinib would be the first and only BTK inhibitor to treat both non-relapsing SPMS and slow disability accumulation. "AAN 2025: Sanofi's tolebrutinib likely to be first BTK inhibitor for the treatment of MS" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site.
Yahoo
08-04-2025
- Health
- Yahoo
Press Release: Tolebrutinib phase 3 data published in NEJM demonstrate benefit on disability progression in multiple sclerosis
Tolebrutinib phase 3 data published in NEJM demonstrate benefit on disability progression in multiple sclerosis Results from the HERCULES phase 3 study showed delay in disability progression in people living with non-relapsing secondary progressive multiple sclerosis Tolebrutinib has the potential to be the first therapy to modulate immunologic drivers of chronic inflammation behind the blood–brain barrier, a key driver of disability accumulation in MS Tolebrutinib is being evaluated under priority review in the US with a target action date of 28 September 2025; regulatory submission dossier is under review in the EU with a decision expected in Q1 2026 Paris, April 8, 2025. The New England Journal of Medicine (NEJM) published positive results from the HERCULES phase 3 study demonstrating that tolebrutinib delayed disability progression in people with non-relapsing secondary progressive multiple sclerosis (nrSPMS), where there are currently no treatment options approved. These findings further support the differentiated mechanism of oral, brain-penetrant tolebrutinib, targeting disability progression independent of relapse activity. These results were first presented at the ECTRIMS conference on September 20, 2024 in Copenhagen, Denmark and further analyses were also presented today during the Clinical Trials Plenary Session at the 2025 Annual Meeting for the American Academy of Neurology (AAN) in San Diego, California. Vice Chair of Research at Cleveland Clinic's Neurological Institute, Cleveland, Ohio, US, and chair of the HERCULES global steering committee'Tolebrutinib represents a new class of therapy for the treatment of multiple sclerosis. In this large phase 3 study, tolebrutinib was found to slow the progression of disability in a subset of multiple sclerosis for which we have no approved therapies – non-relapsing secondary progressive disease. The results of this study signal a new chapter in multiple sclerosis because we finally found a potential way to treat non-relapsing secondary progressive forms.'Dr Fox is a paid advisor to Sanofi for the HERCULES study. Global Head of Neurology Development'By targeting disability progression mechanisms behind the blood-brain barrier, tolebrutinib has the potential to be a practice-changing therapeutic option for people living with multiple sclerosis. The data published in NEJM support our larger commitment to the multiple sclerosis patient community, transforming the treatment paradigm to defy disability across the disease spectrum.' The HERCULES data demonstrated that tolebrutinib delayed the time to onset of 6-month confirmed disability progression (CDP) by 31% compared to placebo (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.55-0.88; p=0.003). Additionally, results from the GEMINI 1 and 2 phase 3 studies, evaluating tolebrutinib in people with relapsing multiple sclerosis (RMS) were also published in NEJM and presented today during the Clinical Trials Plenary Session at the AAN 2025 Annual Meeting. The GEMINI 1 and 2 results did not show superiority on the primary endpoint of reducing annualized relapse rate (ARR) over teriflunomide. The ARR during the study period was 0.13 in the tolebrutinib group and 0.12 in the teriflunomide group in GEMINI 1 (adjusted rate ratio, 1.06; 95% CI 0.81-1.39; p=0.67) and was 0.11 in both groups in GEMINI 2 (adjusted rate ratio, 1.00; 95% CI 0.75-1.32; p=0.98). A pooled analysis for a key secondary endpoint, not controlled for multiplicity, showed that tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29% versus teriflunomide (HR 0.71; 95% CI 0.53 to 0.95). Tolebrutinib was generally well-tolerated across all arms of the studies for all participants. In HERCULES, liver enzyme elevations (>3xULN) were observed in 4.0% of participants receiving tolebrutinib compared with 1.6% in the placebo group. A small (0.5%) proportion of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, all occurring within the first 90 days of treatment. All but one case of liver enzyme elevations resolved without further medical intervention. Prior to the implementation of more frequent liver enzyme monitoring following treatment initiation, one participant in the tolebrutinib arm received a liver transplant and died due to post-operative complications. The implementation of more frequent liver monitoring may help to mitigate serious liver sequelae. Other deaths in the study were assessed as unrelated to treatment by investigators; deaths were even across the placebo and tolebrutinib arms at 0.3%. In an analysis of the GEMINI 1 and 2 pooled safety data, adverse events observed between the tolebrutinib and teriflunomide arms were generally balanced. Liver enzyme elevations (>3xULN) were observed in 5.6% of participants receiving tolebrutinib compared to 6.3% in the teriflunomide arms. A small (0.5%) proportion of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, all occurring within the first 90 days of treatment. Deaths were balanced across the teriflunomide and tolebrutinib arms, at 0.2% and 0.1% respectively, and were assessed as unrelated to treatment by the investigators. The safety and efficacy of tolebrutinib have not been determined by any regulatory authority. The regulatory submission for tolebrutinib to treat nrSPMS and to slow disability accumulation independent of relapse activity in adult patients is being evaluated under priority review by the US Food and Drug Administration with a target action date of September 28, 2025. A regulatory submission is also under review in the EU. About multiple sclerosis Multiple sclerosis is a chronic, immune-mediated disease of the central nervous system that may result in accumulation of irreversible disabilities over time. The physical and cognitive disability impairments translate into gradual deterioration of health status, impacting patients' quality of life. Disability accumulation remains the significant unmet medical need in MS. To date, the primary target of currently approved medicines has been peripheral B and T cells, while innate immunity within the CNS, which is believed to drive disability accumulation, remains largely unaddressed. Currently approved or late-stage medicines being tested for MS mainly target the adaptive immune system and/or do not act directly within the central nervous system to drive clinical benefit. Living with nrSPMS refers to people with MS who have stopped experiencing relapses but continue to accumulate disability, experienced as symptoms such as fatigue, cognitive impairment, balance and gait impairment, loss of bowel and/or bladder function, sexual disfunction, amongst others. About tolebrutinib Tolebrutinib is an investigational, oral, brain-penetrant and bioactive Bruton's tyrosine kinase (BTK) inhibitor specifically designed to target smoldering neuroinflammation, a key driver of disability progression in multiple sclerosis. Unlike conventional MS therapies that primarily address peripheral inflammation, tolebrutinib crosses the blood-brain barrier to achieve therapeutic cerebrospinal fluid concentrations, allowing it to modulate both B-lymphocytes and disease-associated microglia within the central nervous system. This mechanism is thought to directly address the underlying pathology of progressive MS by targeting the inflammatory processes that contribute to neurodegeneration and disability accumulation. Tolebrutinib was previously granted breakthrough therapy designation by the FDA, based on positive results from the HERCULES phase 3 study in adults with non-relapsing secondary progressive MS. Tolebrutinib is being evaluated in a phase 3 clinical study for the treatment of primary progressive multiple sclerosis and its safety and efficacy have not been determined by any regulatory authority worldwide. For more information on tolebrutinib clinical studies, please visit Tolebrutinib represents Sanofi's commitment to developing innovative treatments that address the underlying causes of neurological diseases and potentially transform the treatment landscape. Standing at the intersection of neurology and immunoscience, Sanofi is focused on improving the lives of those living with serious neuro-inflammatory and neuro-degenerative conditions including MS, chronic inflammatory demyelinating polyneuropathy, Alzheimer's disease, Parkinson's disease, age-related macular degeneration, and other neurological diseases. The neurology pipeline currently has several projects in phase 3 studies across 7 indications. About HERCULES HERCULES (clinical study identifier: NCT04411641) was a double-blind randomized phase 3 study evaluating the efficacy and safety of tolebrutinib in patients with nrSPMS. At baseline, nrSPMS was defined as having a SPMS diagnosis with an expanded disability status scale (EDSS) between 3.0 and 6.5, no clinical relapses for the previous 24 months and documented evidence of disability accumulation in the previous 12 months. Participants were randomized (2:1) to receive either an oral daily dose of tolebrutinib or matching placebo for up to approximately 48 months. The primary endpoint was 6-month CDP defined as the increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.0, or the increase of ≥0.5 point when the baseline EDSS score was >5.0. Secondary endpoints included time to onset of 3-month CDP as assessed by EDSS score, total number of new or enlarging T2 hyperintense lesions as detected by MRI, time to onset of confirmed disability improvement, 3-month change in 9-hole peg test and T25-FW test as well as the safety and tolerability of tolebrutinib. About GEMINI 1 and 2 GEMINI 1 (clinical study identifier: NCT04410978) and GEMINI 2 (clinical study identifier: NCT04410991) were double-blind randomized phase 3 studies evaluating the efficacy and safety of tolebrutinib compared to teriflunomide in patients with RMS. Participants were randomized in both studies (1:1) to receive either tolebrutinib and placebo daily or 14 mg teriflunomide and placebo. The primary endpoint for both studies was the annualized relapse rate for up to approximately 36 months defined as the number of confirmed adjudicated protocol defined relapses. Secondary endpoints included time to onset of CDW, confirmed over at least 6 months, defined as an increase of ≥1.5 points from the baseline EDSS score when the baseline score is 0, an increase of ≥1.0 point from the baseline EDSS score when the baseline score is 0.5 to ≤5.5 or an increase of ≥0.5 point from the baseline EDSS score when the baseline score was >5.5 in addition to the total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from baseline through the end of study, the total number of Gd-enhancing T1 hyperintense lesions as detected by MRI from baseline through the end of study and the safety and tolerability of tolebrutinib. About Sanofi We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people's lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our is listed on EURONEXT: SAN and NASDAQ: SNY Media RelationsSandrine Guendoul | +33 6 25 09 14 25 | Evan Berland | +1 215 432 0234 | Nicolas Obrist | +33 6 77 21 27 55 | Léo Le Bourhis | +33 6 75 06 43 81 | Victor Rouault | +33 6 70 93 71 40 | Timothy Gilbert | +1 516 521 2929 | Investor RelationsThomas Kudsk Larsen | +44 7545 513 693 | Alizé Kaisserian | +33 6 47 04 12 11 | Felix Lauscher | +1 908 612 7239 | Keita Browne | +1 781 249 1766 | Nathalie Pham | +33 7 85 93 30 17 | Tarik Elgoutni | +1 617 710 3587 | Thibaud Châtelet | +33 6 80 80 89 90 | Yun Li | +33 6 84 00 90 72 | Sanofi forward-looking statementsThis press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. 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The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under 'Risk Factors' and 'Cautionary Statement Regarding Forward-Looking Statements' in Sanofi's annual report on Form 20-F for the year ended December 31, 2024. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. All trademarks mentioned in this press release are the property of the Sanofi group. Attachment Press ReleaseSign in to access your portfolio
Yahoo
08-04-2025
- Health
- Yahoo
Press Release: Tolebrutinib phase 3 data published in NEJM demonstrate benefit on disability progression in multiple sclerosis
Tolebrutinib phase 3 data published in NEJM demonstrate benefit on disability progression in multiple sclerosis Results from the HERCULES phase 3 study showed delay in disability progression in people living with non-relapsing secondary progressive multiple sclerosis Tolebrutinib has the potential to be the first therapy to modulate immunologic drivers of chronic inflammation behind the blood–brain barrier, a key driver of disability accumulation in MS Tolebrutinib is being evaluated under priority review in the US with a target action date of 28 September 2025; regulatory submission dossier is under review in the EU with a decision expected in Q1 2026 Paris, April 8, 2025. The New England Journal of Medicine (NEJM) published positive results from the HERCULES phase 3 study demonstrating that tolebrutinib delayed disability progression in people with non-relapsing secondary progressive multiple sclerosis (nrSPMS), where there are currently no treatment options approved. These findings further support the differentiated mechanism of oral, brain-penetrant tolebrutinib, targeting disability progression independent of relapse activity. These results were first presented at the ECTRIMS conference on September 20, 2024 in Copenhagen, Denmark and further analyses were also presented today during the Clinical Trials Plenary Session at the 2025 Annual Meeting for the American Academy of Neurology (AAN) in San Diego, California. Vice Chair of Research at Cleveland Clinic's Neurological Institute, Cleveland, Ohio, US, and chair of the HERCULES global steering committee'Tolebrutinib represents a new class of therapy for the treatment of multiple sclerosis. In this large phase 3 study, tolebrutinib was found to slow the progression of disability in a subset of multiple sclerosis for which we have no approved therapies – non-relapsing secondary progressive disease. The results of this study signal a new chapter in multiple sclerosis because we finally found a potential way to treat non-relapsing secondary progressive forms.'Dr Fox is a paid advisor to Sanofi for the HERCULES study. Global Head of Neurology Development'By targeting disability progression mechanisms behind the blood-brain barrier, tolebrutinib has the potential to be a practice-changing therapeutic option for people living with multiple sclerosis. The data published in NEJM support our larger commitment to the multiple sclerosis patient community, transforming the treatment paradigm to defy disability across the disease spectrum.' The HERCULES data demonstrated that tolebrutinib delayed the time to onset of 6-month confirmed disability progression (CDP) by 31% compared to placebo (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.55-0.88; p=0.003). Additionally, results from the GEMINI 1 and 2 phase 3 studies, evaluating tolebrutinib in people with relapsing multiple sclerosis (RMS) were also published in NEJM and presented today during the Clinical Trials Plenary Session at the AAN 2025 Annual Meeting. The GEMINI 1 and 2 results did not show superiority on the primary endpoint of reducing annualized relapse rate (ARR) over teriflunomide. The ARR during the study period was 0.13 in the tolebrutinib group and 0.12 in the teriflunomide group in GEMINI 1 (adjusted rate ratio, 1.06; 95% CI 0.81-1.39; p=0.67) and was 0.11 in both groups in GEMINI 2 (adjusted rate ratio, 1.00; 95% CI 0.75-1.32; p=0.98). A pooled analysis for a key secondary endpoint, not controlled for multiplicity, showed that tolebrutinib delayed the time to onset of 6-month confirmed disability worsening by 29% versus teriflunomide (HR 0.71; 95% CI 0.53 to 0.95). Tolebrutinib was generally well-tolerated across all arms of the studies for all participants. In HERCULES, liver enzyme elevations (>3xULN) were observed in 4.0% of participants receiving tolebrutinib compared with 1.6% in the placebo group. A small (0.5%) proportion of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, all occurring within the first 90 days of treatment. All but one case of liver enzyme elevations resolved without further medical intervention. Prior to the implementation of more frequent liver enzyme monitoring following treatment initiation, one participant in the tolebrutinib arm received a liver transplant and died due to post-operative complications. The implementation of more frequent liver monitoring may help to mitigate serious liver sequelae. Other deaths in the study were assessed as unrelated to treatment by investigators; deaths were even across the placebo and tolebrutinib arms at 0.3%. In an analysis of the GEMINI 1 and 2 pooled safety data, adverse events observed between the tolebrutinib and teriflunomide arms were generally balanced. Liver enzyme elevations (>3xULN) were observed in 5.6% of participants receiving tolebrutinib compared to 6.3% in the teriflunomide arms. A small (0.5%) proportion of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, all occurring within the first 90 days of treatment. Deaths were balanced across the teriflunomide and tolebrutinib arms, at 0.2% and 0.1% respectively, and were assessed as unrelated to treatment by the investigators. The safety and efficacy of tolebrutinib have not been determined by any regulatory authority. The regulatory submission for tolebrutinib to treat nrSPMS and to slow disability accumulation independent of relapse activity in adult patients is being evaluated under priority review by the US Food and Drug Administration with a target action date of September 28, 2025. A regulatory submission is also under review in the EU. About multiple sclerosis Multiple sclerosis is a chronic, immune-mediated disease of the central nervous system that may result in accumulation of irreversible disabilities over time. The physical and cognitive disability impairments translate into gradual deterioration of health status, impacting patients' quality of life. Disability accumulation remains the significant unmet medical need in MS. To date, the primary target of currently approved medicines has been peripheral B and T cells, while innate immunity within the CNS, which is believed to drive disability accumulation, remains largely unaddressed. Currently approved or late-stage medicines being tested for MS mainly target the adaptive immune system and/or do not act directly within the central nervous system to drive clinical benefit. Living with nrSPMS refers to people with MS who have stopped experiencing relapses but continue to accumulate disability, experienced as symptoms such as fatigue, cognitive impairment, balance and gait impairment, loss of bowel and/or bladder function, sexual disfunction, amongst others. About tolebrutinib Tolebrutinib is an investigational, oral, brain-penetrant and bioactive Bruton's tyrosine kinase (BTK) inhibitor specifically designed to target smoldering neuroinflammation, a key driver of disability progression in multiple sclerosis. Unlike conventional MS therapies that primarily address peripheral inflammation, tolebrutinib crosses the blood-brain barrier to achieve therapeutic cerebrospinal fluid concentrations, allowing it to modulate both B-lymphocytes and disease-associated microglia within the central nervous system. This mechanism is thought to directly address the underlying pathology of progressive MS by targeting the inflammatory processes that contribute to neurodegeneration and disability accumulation. Tolebrutinib was previously granted breakthrough therapy designation by the FDA, based on positive results from the HERCULES phase 3 study in adults with non-relapsing secondary progressive MS. Tolebrutinib is being evaluated in a phase 3 clinical study for the treatment of primary progressive multiple sclerosis and its safety and efficacy have not been determined by any regulatory authority worldwide. For more information on tolebrutinib clinical studies, please visit Tolebrutinib represents Sanofi's commitment to developing innovative treatments that address the underlying causes of neurological diseases and potentially transform the treatment landscape. Standing at the intersection of neurology and immunoscience, Sanofi is focused on improving the lives of those living with serious neuro-inflammatory and neuro-degenerative conditions including MS, chronic inflammatory demyelinating polyneuropathy, Alzheimer's disease, Parkinson's disease, age-related macular degeneration, and other neurological diseases. The neurology pipeline currently has several projects in phase 3 studies across 7 indications. About HERCULES HERCULES (clinical study identifier: NCT04411641) was a double-blind randomized phase 3 study evaluating the efficacy and safety of tolebrutinib in patients with nrSPMS. At baseline, nrSPMS was defined as having a SPMS diagnosis with an expanded disability status scale (EDSS) between 3.0 and 6.5, no clinical relapses for the previous 24 months and documented evidence of disability accumulation in the previous 12 months. Participants were randomized (2:1) to receive either an oral daily dose of tolebrutinib or matching placebo for up to approximately 48 months. The primary endpoint was 6-month CDP defined as the increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.0, or the increase of ≥0.5 point when the baseline EDSS score was >5.0. Secondary endpoints included time to onset of 3-month CDP as assessed by EDSS score, total number of new or enlarging T2 hyperintense lesions as detected by MRI, time to onset of confirmed disability improvement, 3-month change in 9-hole peg test and T25-FW test as well as the safety and tolerability of tolebrutinib. About GEMINI 1 and 2 GEMINI 1 (clinical study identifier: NCT04410978) and GEMINI 2 (clinical study identifier: NCT04410991) were double-blind randomized phase 3 studies evaluating the efficacy and safety of tolebrutinib compared to teriflunomide in patients with RMS. Participants were randomized in both studies (1:1) to receive either tolebrutinib and placebo daily or 14 mg teriflunomide and placebo. The primary endpoint for both studies was the annualized relapse rate for up to approximately 36 months defined as the number of confirmed adjudicated protocol defined relapses. Secondary endpoints included time to onset of CDW, confirmed over at least 6 months, defined as an increase of ≥1.5 points from the baseline EDSS score when the baseline score is 0, an increase of ≥1.0 point from the baseline EDSS score when the baseline score is 0.5 to ≤5.5 or an increase of ≥0.5 point from the baseline EDSS score when the baseline score was >5.5 in addition to the total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from baseline through the end of study, the total number of Gd-enhancing T1 hyperintense lesions as detected by MRI from baseline through the end of study and the safety and tolerability of tolebrutinib. About Sanofi We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people's lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our is listed on EURONEXT: SAN and NASDAQ: SNY Media RelationsSandrine Guendoul | +33 6 25 09 14 25 | Evan Berland | +1 215 432 0234 | Nicolas Obrist | +33 6 77 21 27 55 | Léo Le Bourhis | +33 6 75 06 43 81 | Victor Rouault | +33 6 70 93 71 40 | Timothy Gilbert | +1 516 521 2929 | Investor RelationsThomas Kudsk Larsen | +44 7545 513 693 | Alizé Kaisserian | +33 6 47 04 12 11 | Felix Lauscher | +1 908 612 7239 | Keita Browne | +1 781 249 1766 | Nathalie Pham | +33 7 85 93 30 17 | Tarik Elgoutni | +1 617 710 3587 | Thibaud Châtelet | +33 6 80 80 89 90 | Yun Li | +33 6 84 00 90 72 | Sanofi forward-looking statementsThis press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions, and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words 'expects', 'anticipates', 'believes', 'intends', 'estimates', 'plans' and similar expressions. 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These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the fact that product candidates if approved may not be commercially successful, the future approval and commercial success of therapeutic alternatives, Sanofi's ability to benefit from external growth opportunities, to complete related transactions and/or obtain regulatory clearances, risks associated with intellectual property and any related pending or future litigation and the ultimate outcome of such litigation, trends in exchange rates and prevailing interest rates, volatile economic and market conditions, cost containment initiatives and subsequent changes thereto, and the impact that global crises may have on us, our customers, suppliers, vendors, and other business partners, and the financial condition of any one of them, as well as on our employees and on the global economy as a whole. The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under 'Risk Factors' and 'Cautionary Statement Regarding Forward-Looking Statements' in Sanofi's annual report on Form 20-F for the year ended December 31, 2024. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. All trademarks mentioned in this press release are the property of the Sanofi group. Attachment Press ReleaseSign in to access your portfolio
