We expect to find that the silent cerebral infarct (SCI) rate is two fold higher in patients treated without caplacizumab. We also expect to find that the rate of mild and major cognitive impairment in patients treated with caplacizumab within 3 days of starting plasma exchange will be lower than patients treated without caplacizumab.
We expect that the differences in cognitive impairment in cases (caplacizumab) versus controls (no caplacizumab) will persist on serial evaluation 1 year later. We also expect that there will be differences in these groups even after adjusting for time since episode and severity of presentation.
We expect to find that SCI and cognitive impairment is associated with worse scores on the health related quality of life instrument (SF-36)
Based on studies in non-TTP populations, we expect to find that the rate of incident stroke over the period of follow up is at least 2 fold higher in patients that have SCI compared with patients who do not have SCI

Start Date01 May 2024

Sponsor / Collaborator-

NCT05876221 / RecruitingNot Applicable

Platelet Response to Caplacizumab in the Treatment of Acquired Thrombotic Thrombocytopenic Purpura

The interpretation of platelet counts has to be revaluated in the light of caplacizumab. By effectively blocking platelet binding sites on VWF-multimers, the nanobody leads to a rapid normalization of the platelet count within 3 to 4 days. Most importantly, caplacizumab uncouples platelet counts from ADAMTS13 activity and thereby launches unprecedented thrombocyte dynamics, with potential pitfalls for over- and undertreatment.
A relevant number of patients responds to caplacizumab with a brisk increase in platelet count, followed by a marked dip of platelets (patient on the left). This may mislead treating physicians into re-intensifying therapy, with a respective risk for adverse side-effects and complications. Taken together, these observations call for reliable descriptions and the identification of predictive parameters to predict the platelet response upon administration of caplacizumab in a large patient cohort. Here, PREDICT-2020 is designed as a retrospective study to specifically address the following aspects:
Identifying and describing clusters of platelet responses to caplacizumab
Identifying potential pitfalls for treating physicians
Predicting the individual thrombocyte response
Correlating platelet responses with individual patient outcome

Start Date30 Oct 2023

Sponsor / Collaborator

Universities of Cologne

NCT05468320 / RecruitingPhase 3

An Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Caplacizumab and Immunosuppressive Therapy Without Firstline Therapeutic Plasma Exchange in Adults With Immune-mediated Thrombotic Thrombocytopenic Purpura

This is a single group, treatment, Phase 3, open-label, single-arm study to evaluate the efficacy and safety of caplacizumab and immunosuppressive therapy (IST) without firstline therapeutic plasma exchange (TPE) with primary endpoint of remission in male and female participants aged 18 to 80 years with immune-mediated thrombotic thrombocytopenic purpura (iTTP).
The anticipated study duration per participant without a recurrence while on therapy is maximum 24 weeks (ie, approximately 1 day for screening + maximum 12 weeks of treatment for the presenting episode + 12 weeks of follow-up). Participants will have daily assessments during hospitalization and weekly visits for assessments during ongoing treatment with caplacizumab and IST. There will be 3 outpatient visits for assessments during the follow-up period. There will be two additional follow-up visits for participants who do not have ADAMTS13 activity levels of ≥50% at the time of caplacizumab discontinuation.

Start Date21 Nov 2022

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Caplacizumab-YHDP

100 Translational Medicine associated with Caplacizumab-YHDP

100 Patents (Medical) associated with Caplacizumab-YHDP

254

Literatures (Medical) associated with Caplacizumab-YHDP

01 Feb 2024·British journal of haematology

Bortezomib in relapsed/refractory immune thrombotic thrombocytopenic purpura: A single‐centre retrospective cohort and systematic literature review

Review

Author: Ibrahim, Ibrahim F ; Lee, Nicholas C J ; Yates, Sean ; Bavli, Natalie R ; Rambally, Siayareh ; Sarode, Ravi ; Hofmann, Sandra L ; Shen, Yu-Min

Summary:

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life‐threatening haematological condition. Initial treatment involves plasma exchange (PLEX), corticosteroids, caplacizumab and rituximab. In relapsed and refractory cases despite initial treatments, further immune‐modulating therapy includes the proteasome inhibitor, bortezomib. Evidence for bortezomib in this setting is limited to case reports and case series. We report our experience and perform a systematic review of the literature. We identified 21 publications with 28 unique patients in addition to our cohort of eight patients treated with bortezomib. The median age of patients was 44 years (IQR: 27–53) and 69% female. They were usually in an initial, refractory presentation of iTTP where they had received PLEX, corticosteroids, rituximab and another line of therapy. After bortezomib administration, 72% of patients had a complete response, with 85% maintaining a durable response without relapse at the last follow‐up.

01 Jan 2024·Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis

True vs. false immune-mediated thrombotic thrombocytopenic purpura exacerbations: a clinical case in the caplacizumab era

Article

Author: Mahnaz, Shafii Bafti ; Maglione, Raffaele ; Imperatore, Stefano ; Trisolini, Silvia Maria ; Capria, Saveria ; Vitullo, Diana ; Laganà, Alessandro

Acquired thrombotic thrombocytopenic purpura (aTTP) is a medical emergency requiring urgent plasma exchange and immunosuppressive agents. Recently, the therapeutic options have been expanded by the approval of a novel anti-von Willebrand factor (vWF) nanobody, caplacizumab, inhibiting vWF–platelet aggregation. Here, we present a rare case of a patient affected by immune-mediated TTP (iTTP) reporting ischemic stroke caused by a real iTTP exacerbation during caplacizumab administration and subsequent pancytopenia caused by cytomegalovirus (CMV) infection that mimicked another iTTP exacerbation. The case is a real-life example of a not-frequent iTTP exacerbation in the caplacizumab era and of the new management issues arising with the introduction of the new drugs in clinical practice, highlighting the need of new comprehensive response criteria and treatment guidelines.

31 Dec 2023·Platelets

Management of immune thrombotic thrombocytopenic purpura with caplacizumab: a Canadian, single-centre, real-world experience

Article

Author: Buchholz, Megan ; Pavenski, Katerina ; Tse, Brandon

When combined with therapeutic plasma exchange (TPE) and immunosuppression, upfront universal administration of caplacizumab was shown to be effective in the management of immune thrombotic thrombocytopenic purpura (iTTP). However, access to this drug remains challenging in many jurisdictions. We retrospectively review results of a single-institution experience with caplacizumab over a 3-year period. During the study period, we treated 48 patients with iTTP, of which 11 (23%) received caplacizumab. Eight of these 11 patients (73%) were female; the median age was 45 years (IQR 37.0-58.5). All received TPE within 24 h of admission (median 9 exchanges, IQR 7.0-12.5), and high-dose steroids. Caplacizumab was initiated for a median of 6 days after admission (IQR 2.5-8.0) and continued for a median of 26 days (IQR 14.0-33.0). Five patients (45%) had refractory disease at caplacizumab initiation. Ten patients (91%) survived, reaching clinical remission. Platelet normalization was reached with a median of 4 days following caplacizumab initiation (IQR 1.5-4.0). Complications included minor bleeding (n = 1) and local allergic reaction (n = 1). No patients experienced TTP exacerbation; relapse occurred in two patients (18%) over 1-5 years of follow-up. Caplacizumab appeared to be effective and safe, despite delayed initiation and in the setting of refractory disease.

News (Medical) associated with Caplacizumab-YHDP

27 Jan 2023

·www.pharmaceutical-technology.com

Sanofi offers refunds for Cablivi in novel model for rebates

Credit: Getty Images/ IronHeart On January 18, Sanofi launched a new warranty program for its rare blood disorder drug Cablivi (caplacizumab), which tackles value-based agreements in a slightly different way. The program follows the lead of Pfizer’s warranty programs for Panzyga (immune globulin intravenous) and Xalkori (crizotinib), as pharma continues to explore new types of risk sharing agreements. In 2019, Cablivi became the first FDA-approved , nanobody-based medicine for acquired thrombotic thrombocytopenic purpura (aTTP), an ultra-orphan condition that causes blood clots in small blood vessels around the body. The disorder has a reported annual incidence between 1.5 and 6.0 cases per million in Europe. Dr. James George, a research professor at the University of Oklahoma Health Sciences Center, said Cablivi “adds a new aspect to treatment, the prompt recovery of platelets and prompt resolution of transient neurologic symptoms”. In an email to Pharmaceutical Technology , he further described the therapy as “the most important advance for treatment of TTP since the documentation of effectiveness of plasma exchange in 1991”. Before Cablivi’s approval, patients relied on a combination of plasma exchange plus corticosteroids and immunomodulators as the standard of care (SOC) for treatment. Cablivi stops platelets from clumping together, which prevents small clots, and can be used along with other drugs that suppress the immune system. Sanofi ’s eligibility requirements follow a similar model to Pfizer ’s previous programs, with refunds being dependent on lack of clinical outcome in patients. Sanofi’s new warranty program offers institutions a refund for the cost of six doses of a treatment if it is not effective. Any refunds will consider the cheaper option between wholesale acquisition cost (WAC) or actual acquisition cost. Currently, Cablivi’s WAC is $7,300 per single-dose vial kit. A refund up to 12 inpatient doses will also be offered for patients whose disease worsens while receiving treatment. The drug ranks highly for its cost, with a price of $270,000 before rebates and discounts to treat a typical episode of aTTP. Jakub Hlávka, PhD, the executive director of the Healthcare Markets Initiative and Fellow at the University of Southern California Schaeffer Center, suggests the strategy behind this new warranty program could “minimise the [financial and clinical] risk for the provider and for the patient”. Other companies like BioMarin have already announced an intention to offer an outcomes-based warranty program for its hemophilia A drug Roctavian (valoctocogene roxaparvovec). Sanofi’s warranty program According to Hlávka, a warranty program addresses common concerns of unresponsiveness and exacerbation of disease that appear when dealing with highly innovative treatments. With these therapies, there is the possibility of there being no clinical benefit and an emergence of adverse events. Hlávka says healthcare providers often ask, “Should we only pay for some of the patients? Do we know how to identify the right patients?” Consequently, Sanofi may be trying to increase the potential pool of patients who can get initiated on the treatment, and they can deal with the financial consequences later, he adds. As the drug is so expensive, Hlávka proposes that if the warranty program was not offered, the likelihood that patients would get access would be lower. However, Sanofi’s agreement is particularly unique in the way that it measures outcomes. Unlike other contracts, a refund for Cablivi depends on individual clinical outcomes compared to more commonly used population-based outcomes. The documents outline that a refund can only be given if the patient “experiences a platelet count of less than 50 x 10 9 /L, after four days of combined treatment with Cablivi, therapeutic plasma exchange and immunosuppressive therapy” or if a patient experiences “a new drop in platelet count after initial platelet count normalisation (>150 x 10 9 /L), necessitating re‑initiation of therapeutic plasma exchange after having ruled out any causes for the drop in platelet count other than aTTP pathophysiology”. Hlávka explains that this approach makes sense with such a highly expensive drug for rare diseases, as the burden of collecting and recording individual patient outcomes is only possible when dealing with a smaller patient population. “It strikes me as one of the more transparent ways of dealing with the uncertainties that are involved in these highly complicated therapies,” says Hlávka. However, Andrew Cournoyer, Senior Vice President of PRECISIONvalue, said this may make the process slightly more arduous for patients and physicians. “To qualify for a warranty reimbursement, there are three forms that must be filled out and specifically asks for multiple lab values to demonstrate patient response,” he said in an email to Pharmaceutical Technology . “In some regards this can be an obstacle for participation due to the paperwork involved. However, it is consistent in regards that it simply seeks provider attestation opposed to actual documentation,” he added. Designing risk sharing agreements Overall however, this warranty program is similar to previous performance-based risk sharing agreements, says Alex Watt, principal research analyst on GlobalData’s Price Intelligence team. GlobalData is the parent company of Pharmaceutical Technology. The Professional Society for Health Economics and Outcomes Research (ISPOR) defines risk sharing agreements as “an arrangement between a manufacturer and payer/provider that enables access to (coverage/reimbursement of) a health technology subject to specified conditions”. In 2022, the number of risk sharing agreements peaked with 144 agreements being made in the pharmaceutical industry. Over the last few years, as price tags for drugs have continuously increased, the popularity of risk sharing agreements has been increasing at a rate of 24% annual average growth. According to analysis of GlobalData’s PharmOnline (POLI) database, “the ease of finance-based arrangements has led to an overwhelming 79% of agreements being finance-based, ranging from simple discounts to more complex financial arrangements”. Watt says that amongst these finance-based arrangements, the majority are made up by discount schemes, whether compulsory discounts or other types of price negotiations, in order for high-cost/high-innovative drugs to gain access to critical markets. Cournoyer explained that warranty programs allow drug manufacturers to use real-world data to assess whether a drug’s outcomes are worth its costs, and to “put their money where their mouth is”. With shifts in reimbursement that focus on value (as defined by health outcomes and resource use) versus fee-for-service, innovative contracts such as warranties carry more interest, he adds. However, obstacles still remain. Cournoyer highlighted that competitor products with long histories, guideline backing, and provider loyalty still pose a challenge for pharmaceutical companies testing innovative contracts. Furthermore, he said extracting data to validate the criteria for a warranty reimbursement could be an onerous process. Also, the process to actually apply for reimbursement could be similarly difficult. “Payers, providers, and patients will recognise that drug manufacturers need to protect themselves from fraudulent requests, but these steps can be rate-limiting steps to broader adoption,” said Cournoyer. Despite these challenges, Watt predicts that warranty programs could be one of many unique ways to approach risk sharing agreements differently in the coming years. In a report on risk sharing agreements, the authors outlined that, “based on the small number of countries partaking in [risk sharing agreements], there is room to expand so risk-sharing deals can continue to grow and develop their framework in new countries.” Pharma is experimenting with drug warranty programs Comparison of drug warranty programs from major pharmaceutical companies Drug Company Indication Maximum Refund Amount Time limit Number of forms to fill Cablivi Sanofi Acquired thrombotic thrombocytopenic purpura (aTTP) $50,000 90 days 5 Panzyga Pfizer Primary humoral immunodeficiency $50,000 180 days 4 Xalkori Pfizer Metastatic non small cell lung cancer $58,827 120 days 3 Source: Public Information

Drug Approval

09 Jan 2023

·www.prnewswire.com

Foundational RNA and cLNP expert Antonin (Tony) de Fougerolles joins Etherna as independent board member

NIEL, Belgium, Jan. 9, 2023 /PRNewswire/ -- Etherna ("the Company"), a leading mRNA technologies company, announced today that Antonin (Tony) de Fougerolles has joined its board of directors as an independent member. This follows the Company's recent Series B2 financing round to expand investment in its integrated mRNA technology platform and further pursue its new partnership-driven business strategy. Tony is currently the CEO of Evox Therapeutics, an Oxford-based company developing exosome therapeutics, and has an extensive background in mRNA and more specifically LNPs through his roles at Moderna and Alnylam. He has nearly 25 years of biotech R&D experience in building out drug pipelines, and he has played a key role in developing and successfully advancing 3 new drug modalities to the market (mRNA, RNAi, single domain antibodies) and in helping build several multi-billion-dollar companies from start-up stage. As founding Chief Scientific Officer (CSO) at Moderna Therapeutics, he pioneered modified mRNA as a new therapeutic and vaccine drug modality and the mRNA chemistry and delivery systems that form the basis of the approved COVID-19 mRNA vaccines. Prior to that, as VP of Research at Alnylam, he helped develop RNA interference (RNAi) as a new drug modality, including overseeing development of the first approved LNP-based RNAi delivery system and the development of several approved RNAi drugs including inclisiran. Author of over 60 scientific publications and an inventor on over 100 issued US patents, Tony has also a 'Belgian' connection, from his time as CSO at Ablynx (now Sanofi) where he played a key role in the approval of the first single domain antibody drug, caplacizumab. Tony obtained his PhD in Immunology from Harvard University. Since Etherna was founded in 2013, the Company has established an integrated set of proprietary capabilities for end-to-end design, development and manufacture of next-generation mRNA products. These include molecular designs, lipid biochemistry expertise, customized lipid nanoparticle formulations (cLNPs), mRNA-based T cell adjuvants, and advanced manufacturing processes, and overcome the current challenges facing the development of mRNA therapeutics. Etherna's new business model will utilize this suite of capabilities as enablers to deliver superior products for partners in both early-stage research as well as later-stage development for mRNA therapeutics. "Tony is exceptionally qualified to help ensure Etherna's future corporate growth," added Russell Greig, PhD, Chair of Etherna's board of directors. "His addition to the board will add momentum to the company's mission to deliver cutting edge advances in mRNA and LNP technologies for the treatment of unmet medical needs." "I am thrilled to be joining Etherna's board and contributing to its future growth," commented Tony de Fougerolles. "The cLNPs and mRNA manufacturing expertise that the company has developed is world-leading and impressive in both its breadth and novelty. As is increasingly being understood, the ability to robustly deliver mRNA and other genetic medicines to new cell types and tissues is the central element needed to enable their wider application." Marijn Dekkers, Chairman of Novalis LifeSciences, said: "We are excited to have Tony join at this important stage of the Company's development. He is a fantastic addition to the competences we have already gathered on the board. In addition to scientific excellence, he is a proven entrepreneur with an incredible track record of commercializing new modalities and technology platforms." Bernard Sagaert, interim CEO of Etherna said: "We are delighted to have Tony join the board, as he brings, together with Ken, vast experience in cLNPs and mRNA to Etherna, and is well connected in the industry. Having him on board will be invaluable in helping us implement our new business strategy. Strengthening and expanding our significant expertise in designing, synthesizing, and manufacturing cLNPs for a range of prophylactic and therapeutic indications, will enable the Company to accelerate near-term revenue growth through technology licensing and mRNA cGMP manufacturing services for multiple future partners." SOURCE Etherna

VaccinemRNAExecutive Change

29 Nov 2022

·www.sanofi.com

Sanofi to present new clinical data reinforcing novel therapies across rare blood disorders at ASH 2022

Sanofi to present new clinical data reinforcing novel therapies across rare blood disorders at ASH 2022 Quality of life data for efanesoctocog alfa supports its potential as a transformative, best-in-class therapy for hemophilia A Data across hemophilia A, hemophilia B, cold agglutinin disease (CAD), and other conditions featured in 16 presentations Paris , November 30 , 2022 . Data from across Sanofi’s rare blood disorders franchise will be featured in 16 presentations at the 64 th American Society of Hematology (ASH) Annual Meeting & Exposition from December 10-13, 2022. Karin Knobe, MD , PhD Global Head of Clinical Development for Rare Diseases and Rare Blood Disorders at Sanofi “ The Phase 3 results presented at ASH across hemophilia and cold agglutinin disease underscore our ambition to launch four rare blood disorder therapies in four years. We started this year strong and look forward to c arrying th is momentum into 2023 and beyond, with potential treatment advancements we hope will help transform the lives of people living with rare blood disorders . ” Quality of life data from the pivotal XTEND-1 Phase 3 study will be presented at ASH evaluating the effect of investigational therapy efanesoctocog alfa on pain and physical functioning for people with hemophilia A. These findings build on key results that were first presented at the 30th International Society of Thrombosis and Haemostasis (ISTH) Congress. Data from the XTEND-1 study supported the biologics licence application (BLA) for efanesoctocog alfa, which is currently under FDA priority review with a target action date of February 28, 2023. New data to be presented from the ATLAS program for fitusiran, an investigational therapy for the prophylactic treatment of people with hemophilia A or B, with or without inhibitors, will showcase for the first time the hemostatic equivalency of antithrombin lowering in hemophilia A. Hemostatic equivalency is used to better understand how non-factor therapies, such as fitusiran, can help correct the clotting defect in hemophilia. Fitusiran is designed to work by targeting antithrombin, a protein that helps maintain hemostatic balance. Additional fitusiran data will exhibit improvements in health-related quality of life with reduced treatment burden. Qualitative data will outline treatment expectations for people with hemophilia to live an active lifestyle. In an oral presentation, results from the CADENZA phase 3 study, which supported a supplemental BLA currently under FDA priority review for Enjaymo ® (sutimlimab-jome), will review the effect of Enjaymo on patient-reported outcomes and quality of life. Presentations will also report long-term clinical data from the CADENZA study as well as information on the COVID-19 vaccine response among people living with cold agglutinin disease (CAD) being treated with Enjaymo. Data from the pivotal CADENZA and CARDINAL Phase 3 studies recently supported the European Commission approval of Enjaymo. Additional presentations at ASH will highlight other rare blood disorders. Two posters will explore the prevalence and burden of immune thrombocytopenia (ITP), including cognitive impairment. Data evaluating the response to rilzabrutinib, an investigational therapy, when used as an early treatment option for ITP patients will also be shown. Presentations on acquired thrombotic thrombocytopenic purpura (aTTP) include an analysis of the HERCULES Phase 3 study and a presentation of the MAYARI study design that will assess the efficacy and safety profile of Cablivi ® (caplacizumab-yhdp) without plasma exchange in an investigational setting. Cablivi is approved in several geographies in combination with plasma exchange and immunosuppression for the treatment of aTTP in adults. Hemophilia A and B Abstract #2468: Efficacy of Efanesoctocog Alfa on Physical Functioning: Results from the XTEND-1 Phase 3 Clinical Trial in Previously Treated Patients with Hemophilia A Poster Presentation: 6-8 pm CT, Sunday, December 11, 2022 Abstract #2474: Efficacy of Efanesoctocog Alfa on Pain in Patients with Hemophilia A: Results from the XTEND-1 Phase 3 Clinical Trial in Previously Treated Patients with Hemophilia A Poster Presentation: 6-8 pm CT, Sunday, December 11, 2022 Abstract #3788: A Population Pharmacokinetic (PopPK) Model to Characterize Efanesoctocog Alfa (BIVV001) Factor VIII Activity Levels in Patients with Severe Hemophilia A Poster Presentation: 6-8 pm CT, Monday, December 12, 2022 Abstract #2472: Development of a Quantitative Systems Pharmacology Model to Explore Hemostatic Equivalency of Antithrombin Lowering Poster Presentation: 6-8 pm CT, Sunday, December 11, 2022 Abstract #3559: Fitusiran Prophylaxis Improves Health-Related Quality of Life in People with Hemophilia A or B, with or without inhibitors: Results of ATLAS-PPX study Poster Presentation: 6-8 pm CT, Sunday, December 11, 2022 Abstract #3565: Fitusiran Reaches People’s with Hemophilia and Their Caregivers’ Treatment Expectations: Qualitative Semi-Structured Interviews of Participants of ATLAS-OLE Trial (Interim analysis) Poster Presentation: 6-8 pm CT, Sunday, December 11, 2022 Abstract #3566: Patients with Hemophilia and Their Caregivers Prefer Treatment Attributes That Enable a More Active Lifestyle with Lower Risk of Inhibitor Development Poster Presentation: 6-8 pm CT, Sunday, December 11, 2022 Cold Agglutinin Disease Abstract #31: Sutimlimab Provides Sustained Improvements in Patient-Reported Outcomes and Quality of Life in Patients with Cold Agglutinin Disease: Open-Label Extension of the Randomized, Phase 3 CADENZA Study Oral Presentation: 9:30-11 am CT, Saturday, December 10, 2022 Abstract #1201: Sustained Complement C1s Inhibition with Sutimlimab in Patients With Cold Agglutinin Disease Results in Continued Efficacy During Part B of the Randomized Placebo-Controlled Phase 3 CADENZA Study (NCT03347422) Poster Presentation: 5:30-7:30 pm CT, Saturday, December 10, 2022 Abstract #1208: Concomitant Use Of Sutimlimab and COVID-19 Vaccines In Patients With Cold Agglutinin Disease from the Phase 3 CARDINAL and CADENZA Studies Poster Presentation: 5:30-7:30 pm CT, Saturday, December 10, 2022 Abstract #2325: Hemolytic Markers, Mortality, and Thromboembolic Events in Cold Agglutinin Disease (CAD): A Retrospective Analysis of the OPTUM Electronic Health Record Database in the United States Poster Presentation: 6-8 pm CT, Sunday, December 11, 2022 Immune Thrombocytopenia Abstract #2449: Multirefactory Primary Immune Thrombocytopenia in Adults: Prevalence and Burden. Results from the Carmen-France Registry Poster Presentation: 6-8pm CT, Sunday, December 11, 2022 Abstract #2450: Clinical Predictors of Response to Rilzabrutinib Therapy in Patients With Immune Thrombocytopenia: Exploratory Analysis of a Phase 1/2 Study Poster Presentation: 6-8 pm CT, Sunday, December 11, 2022 Abstract #3773: Cognitive Impairment Among Patients With Chronic Immune Thrombocytopenia Poster Presentation: 6-8 pm CT, Monday, December 12, 2022 Acquired Thrombotic Thrombocytopenic Purpura Abstract #1174: A Phase 3 Study to Evaluate the Efficacy and Safety of Caplacizumab Without First-Line Therapeutic Plasma Exchange in Adults With Immune-Mediated Thrombotic Thrombocytopenic Purpura Poster Presentation: 5:30-7:30 pm CT, Saturday, December 10, 2022 Abstract #2493: The Role of ADAMTS13 Activity Levels on Disease Exacerbation or Relapse in Patients With Immune-Mediated Thrombotic Thrombocytopenic Purpura: Post Hoc Analysis of the Phase 3 HERCULES and Post-HERCULES Studies Poster Presentation: 6-8 pm CT, Sunday, December 11, 2022 Abo ut efanesoctocog alf a Efanesoctocog alfa is a novel and investigational recombinant factor VIII therapy that is designed to extend protection from bleeds with once-weekly prophylactic dosing for people with hemophilia A. It builds on the innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN ® polypeptides to extend its time in circulation. It is the first investigational factor VIII therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on current factor VIII therapies. ALTUVIIIO ® is the intended trade name of efanesoctocog alfa in the US. Efanesoctocog alfa is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority. Efanesoctocog alfa is currently under FDA review with a target action date of February 28, 2023. The FDA also granted efanesoctocog alfa Breakthrough Therapy designation in May 2022, – the first factor VIII therapy to receive this recognition – Fast Track designation in February 2021, and Orphan Drug designation in August 2017. Sanofi and Sobi ® collaborate on the development of efanesoctocog alfa. About fitusiran Fitusiran is an investigational, subcutaneously administered small interference RNA (siRNA) therapeutic in development for the prophylactic treatment of people with hemophilia A or B, with or without inhibitors. Fitusiran is designed to lower antithrombin, a protein that inhibits blood clotting, with the goal of promoting thrombin generation to rebalance hemostasis and prevent bleeds. Fitusiran utilizes Alnylam Pharmaceutical Inc.’s ESC-GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability. Fitusiran is currently under clinical investigation and has not been evaluated by any regulatory authority. About Enjaym o ® ( sutimlimab -jome ) Enjaymo is a humanized monoclonal antibody that is designed to selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. By blocking C1s, Enjaymo inhibits the activation of the complement cascade in the immune system and inhibits C1-activated hemolysis in cold agglutinin disease (CAD) to prevent the abnormal destruction of healthy red blood cells. Enjaymo does not inhibit the lectin and alternative pathways. Enjaymo was approved by the U.S. Food and Drug Administration (FDA) in February 2022 as the first and only treatment indicated to decrease the need for red blood cell transfusion due to hemolysis in adults with CAD. Sanofi has filed for an sBLA to add CADENZA (BIVV009-04) clinical data into the label and was granted priority review by the FDA in September 2022. About Cablivi ® ( caplacizumab -yhdp ) Cablivi is a von Willebrand Factor (vWF) antibody fragment, which inhibits the interaction between ultra-large vWF multimers and platelets and, therefore, stops the formation of the micro-clots that can form during an acute episode of acquired thrombotic thrombocytopenia purpura. Cablivi was approved in the European Union in August 2018 and in the United States in February 2019. Use of Cablivi without plasma exchange is currently investigational and has not been evaluated by any regulatory authority. About rilzabrutinib Rilzabrutinib is an oral Bruton’s tyrosine kinase (BTK) inhibitor incorporating Sanofi’s TAILORED COVALENCY ® technology being investigated for the treatment of immune-mediated diseases, including immune thrombocytopenia (ITP). BTK is an intracellular signaling molecule involved in innate and adaptive immune responses related to certain immune-mediated diseases. By inhibiting BTK, rilzabrutinib has the potential to target the underlying disease pathogenesis. Rilzabrutinib is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority. 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 some 100 countries, 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 ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY Media Relations Sandrine Guendoul | + 33 6 25 09 14 25 | sandrine.guendoul@sanofi.com Sally Bain | + 1 617 834 6026 | sally.bain@sanofi.com Kate Conway | + 1 508 364 4931 | kate.conway@sanofi.com Investor Relations Eva Schaefer-Jansen | + 33 7 86 80 56 39 | eva.schaefer-jansen@sanofi.com Arnaud Delépine | + 33 6 73 69 36 93 | arnaud.delepine@sanofi.com Corentine Driancourt | + 33 6 40 56 92 21 | corentine.driancourt@sanofi.com Felix Lauscher | + 1 908 612 7239 | felix.lauscher@sanofi.com Priya Nanduri | + 1 617 764 6418 | priya.nanduri@sanofi.com Nathalie Pham | + 33 7 85 93 30 17 | nathalie.pham@sanofi.com Sanofi Forward-Looking Statements This document 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. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. 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 COVID-19 will 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, 2021. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. Attachment PDF

Phase 3Breakthrough TherapyDrug ApprovalClinical ResultVaccine

100 Deals associated with Caplacizumab-YHDP

External Link

KEGG	Wiki	ATC	Drug Bank
-	Caplacizumab-YHDP	B01AX07	DB06081

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Purpura, Thrombotic Thrombocytopenic	CA	Sanofi-Aventis Canada, Inc.	04 Sep 2020
Thrombotic Thrombocytopenic Purpura, Acquired	EU	Ablynx NV	30 Aug 2018
Thrombotic Thrombocytopenic Purpura, Acquired	IS	Ablynx NV	30 Aug 2018
Thrombotic Thrombocytopenic Purpura, Acquired	LI	Ablynx NV	30 Aug 2018
Thrombotic Thrombocytopenic Purpura, Acquired	NO	Ablynx NV	30 Aug 2018

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Angina, Stable	Phase 2	AT	Ablynx NV	01 Sep 2009
Angina, Stable	Phase 2	BE	Ablynx NV	01 Sep 2009
Angina, Stable	Phase 2	CZ	Ablynx NV	01 Sep 2009
Angina, Stable	Phase 2	DE	Ablynx NV	01 Sep 2009
Angina, Stable	Phase 2	IL	Ablynx NV	01 Sep 2009
Angina, Stable	Phase 2	PL	Ablynx NV	01 Sep 2009
Angina, Stable	Phase 2	CH	Ablynx NV	01 Sep 2009
Angina, Unstable	Phase 2	AT	Ablynx NV	01 Sep 2009
Angina, Unstable	Phase 2	BE	Ablynx NV	01 Sep 2009
Angina, Unstable	Phase 2	CZ	Ablynx NV	01 Sep 2009

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASH2023	Not Applicable	Thrombotic Thrombocytopenic Purpura, Acquired	33	Caplacizumab (Conventional treatment alone)	vnwbjjctwt(xecviapaxm) = hfdsphhikx xqhxysueha (pvteaayzam ) View more	Positive	10 Dec 2023
ASH2023	Not Applicable	Thrombotic Thrombocytopenic Purpura, Acquired	33	Conventional treatment + Caplacizumab	vnwbjjctwt(xecviapaxm) = dyjdovmjvp xqhxysueha (pvteaayzam )	Positive	10 Dec 2023
ISTH2023	Not Applicable	Purpura, Thrombotic Thrombocytopenic	505	Caplacizumab	unequzfctc(fiafnkjpdc) = Our study shows that bleeding is a common complication of Caplacizumab, which decreases the VWF levels and increases bleeding risk unkixrxqaq (twyozntfib )	-	24 Jun 2023
EHA2023	Not Applicable	Thrombotic Thrombocytopenic Purpura, Acquired	60	CAPLACIZUMAB (Patients ≥60 years)	vtklhpleob(yvezgzrdwn) = one patient ≥60 years died on day 12 after diagnosis due to multiorgan failure that was not considered caplacizumab-related, but progression of iTTP jswlhabbgz (vwsyzjgnhy ) View more	-	08 Jun 2023
EHA2023	Not Applicable	Thrombotic Thrombocytopenic Purpura, Acquired	60	CAPLACIZUMAB (Patients <60 years)		-	08 Jun 2023
NCT04985318 (Pubmed)	Not Applicable	Thrombotic Thrombocytopenic Purpura, Acquired First line	-	Caplacizumab	uzhbmblgey(glbcrmtrrr) = yyvjtnovks nlfsoeowts (jtuszujfwe ) View more	-	22 Dec 2022
NCT04074187 (Pubmed)	Phase 2/3	Thrombotic Thrombocytopenic Purpura, Acquired	21	Caplacizumab 10mg	ylgudyjxvf(yngztzoemc) = gmfukgqcjb qdmtuswfgp (mutbkmhhpo )	Positive	24 Nov 2022
NCT04985318 (REACT-2020, ASN2022)	Not Applicable	Thrombotic Thrombocytopenic Purpura, Acquired First line ADAMTS13 activity below 10 percent \| relapsing thrombotic microangiopathy	-	Caplacizumab	ktajtwclqc(aexstbxzpb) = txrccviego gmnfggyshj (vulvonksws )	Positive	03 Nov 2022
NCT04985318 (REACT-2020, ASN2022)	Not Applicable		-	Standard of care without Caplacizumab	ktajtwclqc(aexstbxzpb) = uvhokujqgx gmnfggyshj (vulvonksws )	Positive	03 Nov 2022
NCT02878603 (HERCULES, Pubmed)	Phase 3	Thrombotic Thrombocytopenic Purpura, Acquired	104	Caplacizumab+TPE+IST	zvfvzyfsrx(sssaftrdvh) = cxanmodftb ivpnknlleb (ybxqniaetx ) View more	Positive	22 Sep 2022
NCT02878603 (HERCULES, Pubmed)	Phase 3	Thrombotic Thrombocytopenic Purpura, Acquired	104	Placebo+TPE+IST	zvfvzyfsrx(sssaftrdvh) = zxytidyrad ivpnknlleb (ybxqniaetx )	Positive	22 Sep 2022
Milan TTP Registry (ISTH2022)	Not Applicable	Thrombotic Thrombocytopenic Purpura, Acquired	26	Caplacizumab	goyrtebtmd(htdsslphpp) = ojxdouulcv ebqoakhxvk (bkxidcfynk )	Positive	09 Jul 2022
NCT04074187 (ASH2021) Manual	Phase 2/3	Thrombotic Thrombocytopenic Purpura, Acquired	21	Caplacizumab	imjzaqrbgz(uqczudmfaf) = efgfegkynj lyiklmppjb (aokistxnof ) View more	Positive	05 Nov 2021
ASN2021	Not Applicable	Thrombotic Thrombocytopenic Purpura, Acquired ADAMTS13 inhibitor \| ADAMTS13 enzyme activity	-	Caplacizumab	afylbnggob(ylessmgavt) = xijkdzgbjy kdbacxyjlt (imxyrzicgc ) View more	Positive	27 Oct 2021

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