Author｜Gray Rabbit
Autoimmune drugs are the second largest pharmaceutical market, only after oncology drugs. According to a Frost & Sullivan report, the global autoimmune disease drug market is estimated at2030will reach by the year1767Billion US dollars.
Such a huge market has also become the target of pursuit for major pharmaceutical companies. AbbVie, with Humira,SkyriziAndRinvoqRanked as the leader in autoimmune diseases, Johnson & Johnson has successively...Remicade、Simponi/ Simponi Aria、StelaraAndTremfyaHeavyweight drugs such as multiple sclerosis blockbuster drugs from Roche.Ocrevus、Sanofi occupies an important position in the autoimmune field with Dupilumab, and Novartis hasCosentyx、Promacta/Revolade、KesimptaAndXolairHeavyweight drugs like autoimmune drugs are not to be underestimated.
AbbVie: Skyrizi Expected to Break Through $11 BillionOn October 30, AbbVie announced its 2024 Q3 financial results, with net revenue in the third quarter increasing by 3.8% year-over-year to $14.46 billion. From a business segment perspective,Autoimmune, Oncology, Neuroscience, and Aesthetics contributed separately.$7.046 billion (+3.9%)、USD 1.687 billion (+11.6%), USD 2.363 billion (+15.6%), USD 1.239 billion (-0.1%).In the autoimmune field, Humira's market share has been impacted by generic drugs, with single-quarter revenue further declining to22.27Billion USD (-37.2%), among which, the U.S. market17.65Billion US dollars (-41.6%), Markets outside the United States4.62Billion USD (-12.4%）。Skyrizi(Lisencekimab) andRinvoq(Upadacitinib) is a rising star in AbbVie's autoimmune disease business, rapidly filling the revenue gap left by Humira's patent cliff.SkyriziThird-Quarter Sales Increase Year-over-Year50.8%To32.05billion dollars, with an estimated annual revenue exceeding110Billion US dollars.RinvoqThird-Quarter Sales Increased Year-over-Year45.3%To16.14billion dollars, and the full-year revenue is expected to exceed50Billion US dollars.SkyriziA cytokine targeting inflammatory processes, originally developed by Boehringer IngelheimIL23Monoclonal antibody drugs, which can work by binding toIL-23 p19Selective blockade by subunit bindingIL-23。2016Year, AbbVie with5.95Acquired the global commercialization rights for Risankizumab from Boehringer Ingelheim for an upfront payment of USD billion.SkyriziIn2019Year4It was approved for marketing in the United States in the month, and the currently approved indications include psoriasis, psoriatic arthritis, and Crohn's disease, etc., this year6Month3Day,AbbVie Submits New Indication Applications for Risankizumab Injection and Subcutaneous Formulation in China, Application Officially Received and Under Review by the Center for Drug Evaluation of the National Medical Products Administration; Speculated to Be Related to Ulcerative ColitisRinvoq(Upadacitinib) is an orally administered drug developed by AbbVie.JAK1Inhibitor,2019Year8First approved for marketing in the U.S. in [Month], for patients with an inadequate response or intolerance to methotrexate (MTX-IR) Moderate to Severe Active Rheumatoid Arthritis (RA) Treatment of adult patients.In February 2022, Rinvoq was approved for marketing in China to treat adult and adolescent patients aged 12 years and above with moderate to severe atopic dermatitis (AD). Currently, the approved indications for Rinvoq include rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, andModerate to severe ulcerative colitis (UC, adults), etc.In addition, AbbVie has many novel pipelines under research in the autoimmune field, including...Including oralNLRX1AgonistABBV-113，RIPKInhibitorABBV-668、ICOS/CD28Dual InhibitorALPN-101And IL-1α And IL-1β Bivalent Structural Domain ImmunoglobulinLutikizumabetc.LutikizumabCurrently in clinical2/3Period, used for the treatment of hidradenitis suppurativa (HS) and ulcerative colitis.In January this year, AbbVie announced the phase 2 results of Lutikizumab, which showed that adult patients with moderate to severe HS who had previously failed anti-TNF treatment received lutikizumab 300 mg every other week or 300 mg weekly.Compared with placebo, a higher HS clinical remission (HiSCR 50) was achieved at week 16 as the primary endpoint (59.5% vs 35.0%).Based on these data, AbbVie will advance the clinical program of lutikizumab for the treatment of HS into Phase 3 (Figure 1) [1].Figure 1. Phase 2 Results of LutikizumabJohnson & Johnson: Tremfya Successfully Takes the BatonNipocalimab: The Rising Star in Autoimmunity2024Year10Month15Johnson & Johnson Releases Q3 Financial ReportQ3Global Revenue225USD billion, year-on-year growth5.2%。By business division, pharmaceuticals businessQ3Revenue146Billion USD, year-on-year growth4.9%, Year-on-year growth in operating revenue6.3%，Growth in the field of oncologyDarzalex（daratumumab）、Erleada（apalutamide）、Carvykti（ciltacabtagene autoleucel）、In the Field of ImmunologyTremfya（Guselkumab）, in the field of neuroscienceSpravto(Esketamine) and the field of pulmonary hypertensionOpsumit（macitentan) Promote.Autoimmune drugs are the core business of Johnson & Johnson, mainly includingStelara(Ustekinumab),Tremfya、Remicade(Infliximab) andSimponi/ Simponi Aria(Golimumab), etc.Stelara, developed by Johnson & Johnson, is the first fully human IgG1k monoclonal antibody against IL-12/23. As Johnson & Johnson's key autoimmune drug, its sales exceeded $10 billion for the first time in 2023, reaching $10.858 billion.However, Stelara is facing patent expiration issues, with its U.S. patent protection having expired in September 2023, and its sales have already declined this year.Revenue in Q3 2024 decreased by 6.6% to $2.6 billion.Fortunately, Tremfya, developed by Janssen Pharmaceuticals under Johnson & Johnson, shows great potential to succeed Stelara. Tremfya is a humanized monoclonal antibody targeting the p19 subunit of IL-23.The product was approved by the FDA in 2017 for the treatment of adult patients with moderate to severe plaque psoriasis.On September 11 this year,TremfyaNew Indication for Treating Adult Patients with Moderate to Severe Active Ulcerative Colitis (UC) Approved by FDA for Marketing, a chronic large intestine disease characterized by inflammation of the colon's inner lining.TremfyaIs the first and only approved fully human dual-action monoclonal antibody., which can block IL-23 and also bind to CD64, a receptor on the cells that produce IL-23 [2].In 2021, Tremfya's sales exceeded $2 billion for the first time, reaching $2.668 billion in 2022, and growing by 17.9% year-over-year to $3.147 billion in 2023.Sales in the first three quarters of this year have reached 2.714 billion US dollars, and the recently approved new indication for UC is expected to further increase its sales.。Besides, another autoimmune drug from Johnson & JohnsonnipocalimabShowing great potential,Nipocalimab is an FcRn monoclonal antibody drug that Johnson & Johnson introduced from Momenta for $6.5 billion.NipocalimabThe2PeriodDAHLIASThe study results showed that patients with moderate to severe xerophthalmia (SjD) UndergoingnipocalimabAfter treatment, key indicators of disease activity improved, andIgGSignificantly Reduced77%The above.Based on the results of the Phase 2 DAHLIAS study, Nipocalimab has been granted Breakthrough Therapy Designation (BTD) by the U.S. FDA for the treatment of adult patients with moderate to severe dry syndrome, a debilitating and chronic autoantibody disease with a high prevalence rate, for which there are currently no approved advanced treatment options available.(Figure 2) [3]。Figure 2. Nipocalimab Granted FDA Breakthrough Therapy Designation (BTD)Nipocalimab is the only investigational therapy in SjD to receive this designation.This is the second time Nipocalimab has received a Breakthrough Therapy Designation. The first was in February, when Nipocalimab was approved for treating alloimmunized pregnant women at high risk of severe fetal and neonatal hemolytic disease (HDFN).Roche: Ocrevus Subcutaneous Injection ApprovedXolair: Old Drug, New Use10Month23Recently, Roche announced its Q3 report, showing pharmaceutical sales for the first nine months.343 CHF billion (387.6Billion USD, according to1Swiss Franc=1.13USD calculation), growth7%, Basic Business (excludingCOVID-19) Growth9%; In the third quarter, sales growth was achieved.9%(Calculated in Swiss Francs6%), the same as in the second quarter.The growth of the pharmaceuticals business was mainly driven by Vabysmo(Severe eye diseases),Phesgo(Breast Cancer),Ocrevus(Multiple Sclerosis),Hemlibra(Hemophilia) andPolivy(Sales growth of blood cancer).Roche's main autoimmune products include CD20 monoclonal antibody Ocrevus, IL-6 monoclonal antibody Actemra/RoActemra, and IgE monoclonal antibody Xolair, among others.。Ocrevus is a重磅 antibody therapy targeting CD20 developed by Roche.Is the first and only disease-modifying treatment (DMT) for multiple sclerosis (MS) that benefits patients with either relapsing or primary progressive multiple sclerosis (RMS or PPMS)., was approved for marketing in the United States in 2017.In September this year, the FDA approved Ocrevus Zunovo™ (ocrelizumab and hyaluronidase-ocsq) based on Phase 3 OCARINA II trial data.Subcutaneous InjectionFor the treatment of adult relapsing multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting multiple sclerosis, and active secondary progressive multiple sclerosis; as well as primary progressive MS in adults.Ocrevus Zunovo Is forCD20 Ocrelizumab and Hyaluronidase-ocsq(A substance that can increase subcutaneous(SC) The combination of endoglycosidase for tissue transparency.The product is administered twice a year, each time10Minutes, subcutaneous injection.Ocrevus, currently Roche's best-selling drug, achieved sales of 5.056 billion Swiss francs (5.713 billion US dollars) in the first nine months of this year, representing a 9% year-on-year increase.(Figure 3) [4].Figure 3. Roche's Top Three Drugs by Sales in Q3 2024Actemra/RoActemraInitially byChugaiDeveloped and subsequently co-developed and marketed with Roche for binding purposes.sIL-6RAndmIL-6RMonoclonal antibody drugs, successively in2005Year,2009Year,2010Year and2013Approved for marketing in Japan, the European Union, the United States, and China in [Year], for the treatment of rheumatoid arthritis (RA), etc.Actemra/RoActemraSales exceeded $2 billion for the first time in 2017 and have continued to grow steadily. During the COVID-19 pandemic, tocilizumab...Included in China's COVID-19 treatment guidelines, sales reached $3.96 billion in 2021. However, with the weakening impact of COVID-19 and patent expiration, Actemra/RoActemraSales began to decline in the past two years, with sales reaching 26.3 in 2023.CHF billion (29.7Billion USD), sales in the first nine months of this year reached 1.948 billionSwiss Franc（22(Billion USD).XolairIt was developed by Roche and Novartis to target and blockIgEAntibody drug. By reducing freeIgE`, down-regulation of high affinity`IgEReceptors and restriction of mast cell degranulation,XolairMinimize the release of mediators throughout the allergic inflammatory cascade.Xolair is an old drug, first approved by the FDA in June 2003 for subcutaneous injection to treat moderate to severe persistent asthma in patients aged 12 years and older. Although Xolair's patents have expired in both China and the US, it continues to gain momentum with newly approved indications.As of February this year, Xolair received FDA approval in the United States for the treatment of adults and children over 1 year old who may experience immunoglobulin E (IgE)-mediated allergic reactions due to accidental exposure to one or more foods. This approval was based on the positive data from the OUtMATCH study. Notably, this is the first and only FDA-approved drug for reducing allergic reactions to one or more foods.。With the approval of new indications,XolairThe sales volume was still considerable, according to Roche's financial report,XolairBefore9Monthly sales volume is17.37Million Swiss Francs (19.63Billion US dollars).In addition, Roche has also laid out in the immunology field for the treatment of multiple sclerosis.BTKInhibitorFenebrutinib, for the treatment of ulcerative colitisTL1AMonoclonal AntibodyRG6631etc.Fenebrutinib is an orally administered drug developed by Roche.Reversible and Non-CovalentBTKInhibitor, canBlock MicrogliaFc γReceptor (FcγR) Activation of harmful effects, including the release of cytokines and chemokines, microglial aggregation, and neurite damage in different human brain cell systems.(Figure4）[5]。Figure 4. Schematic diagram of the effects of fenebrutinib on B cell and microglial pathways9Month4Date, Roche announcedFenebrutinibThe2PeriodFENoptaOpen-label Extension (OLE) The latest results of the study. The results show that those who receivedFenebrutinibUp to1Annual treatment of relapsing multiple sclerosis (RMS) The patient maintains a very low level of disease activity, and there is no progression in disability status.Sanofi: Dupilumab Takes the LeadExpected to exceed 13 billion euros2024Year10Month25Recently, Sanofi released2024Financial results for the third quarter of the year.2024In the third quarter of the year (reporting period), the company's revenue134.38EUR billion (approximately141.64Billion USD, according to1Euro=1.054USD calculation), year-on-year growth15.7%(Calculated at fixed exchange rates, the same below).Strong growth in pharmaceuticals business, revenue121.67EUR billion (approximately137.49Billion USD), Year-on-Year Growth16.6%, mainly driven by Dupilumab and vaccines.Dupilumab is Sanofi's重磅 self-immune drug, a targetedIL-4RImmunoglobulinG4Fully human monoclonal antibody of the subclass, successively in2017Year3Month and2020Year6Approved for marketing in the U.S. and China in [Month], becoming the first biologic agent to treat moderate-to-severe atopic dermatitis.Since its approval, the sales of Dupilumab have been increasing year by year.2023Annual sales reached107.15Million euros (approximately121.08Billion USD), mainly due to atopic dermatitis, asthma, and chronic rhinitis.-Sinusitis with Nasal Polyps, Prurigo Nodularis, and Eosinophilic Esophagitis (EoE) The continuous release of clinical needs. This yearQ3Sales reached34.76EUR billion (approximately39.28billion US dollars), plus the first half of this year's61.38EUR billion (approximately69.36Billion USD),Sales for the first nine months have reached96.14100 million euros (approximately108.64billion USD), and the full year is expected to exceed the target previously set by Sanofi.130Sales target of 100 million euros(Figure5）。Figure 5. Dupilumab Sales RevenueThis year, Dupilumab has also made significant progress, such asOn July 3, Dupilumab was approved by the European Medicines Agency (EMA) as an add-on maintenance treatment for patients with uncontrolled chronic obstructive pulmonary disease (COPD) characterized by elevated blood eosinophil levels., including patients who have already been using inhaled corticosteroids (ICS), long-acting beta2 agonists (LABA), and long-acting muscarinic antagonists (LAMA) in combination.9Month27Day, Sanofi USFDAAnd ChinaNMPADupilumab has been approved asCOPDAdd-on maintenance treatment for adults with poorly controlled and eosinophilic phenotype.Dupilumab is the first biologic drug approved in the United States for the treatment of these patients.。FDA The approval was based on two landmark pivotal3Phase Research (BOREASAndNOTUS) Data:They have reached in52Moderate or Severe Within a WeekCOPD Decrease in the Annualized Rate of Deterioration30%And34%The primary endpoint.Compared with placebo, the12After bronchodilator at the same timeFEV1Improvement from Baseline74mLAnd68mL, Continuous52Week. In key secondary endpoints12Zhou He52At the same time, before bronchodilatorFEV1A statistically significant improvement of similar magnitude was observed compared to baseline.[6]。On November 6, Sanofi announced that the European Medicines Agency had approved dupilumab for the treatment of eosinophilic esophagitis (EoE) in children as young as 1 year old.Specifically, the approval covers children aged 1 to 11 years, weighing at least 15 kg, and whose condition is inadequately controlled by, intolerant to, or unsuitable for conventional drug therapy. This expands the initial EU approval for adults and adolescents with EoE.And make dupilumab the first and only drug for treating these young patients.[7]。November 15,Sanofi announces that the U.S. FDA has accepted the resubmissionDupilumabThe supplemental Biologics License Application (sBLA) for review, intended for the treatment of Chronic Spontaneous Urticaria (CSU) in adult and pediatric patients 12 years of age and older who are not adequately controlled by H1 antihistamine therapy.The FDA goal date for a decision is April 18, 2025.In addition to targeting IL-4RDupilumabIn addition, Sanofi has multiple autoimmune drugs in clinical development stages,Including monoclonal antibodies targeting IL-33Itepekimab, CD40L monoclonal antibodyFrexalimab, BTK inhibitors tolebrutinib and rilzabrutinib, as well asOX40L Monoclonal AntibodyAmlitelimab, etc.。ItepekimabDeveloped by Sanofi“First-in-class”TargetedIL-33A Type of PersonIgG4Monoclonal antibodies, by acting onIL-33Reduce airway inflammation and preventILC2Activation of cells. This may help alleviate asthma symptoms and improve lung function.FrexalimabInitially byImmuNextThe research and development is targeted atCD40LThe new monoclonal antibody,2017Year, Sanofi andImmuNextSign an exclusive global licensing agreement to obtainFrexalimabIn the development rights across a range of autoimmune diseases such as lupus and multiple sclerosis. For this, Sanofi will...ImmuNextThe total amount of potential milestone payments may reach5Hundreds of millions of dollars, as well as tiered royalties on product sales in the double-digit range.AmlitelimabInitially byKymabA fully human-derivedOX40LMonoclonal antibodies, through targetingOX40Ligand,amlitelimabAimed at restoring pro-inflammatoryTCells and RegulationTImmune homeostasis between cells.2021Year11Month, Sanofi andKymabReach an agreement to14.5Billion-dollar price for the acquisition ofKymab, willAmlitelimabIncluded in the bag,AmlitelimabCould potentially become the first treatment for a range of immune-mediated and inflammatory diseases, including moderate to severe atopic dermatitis and asthma.Novartis: Cosentyx Up 28% Year-on-Year10Month29Recently, Novartis announced2024In the third quarter of the year, the company achieved revenue128Billion USD, exceeding market expectations118billion dollars, increased from the same period last year10%(Calculated at fixed exchange rates); Total Net Revenue of the Company32 billion dollars, an increase of121%。Among which, the core business revenue51 billion USD, a year-on-year increase of20%, mainly due toEntresto (+26%)、Cosentyx (+28%)、Kisqali (+43%)、Kesimpta (+28%)、Pluvicto (+50%) AndLeqvio (+119%)The growth in product sales such as...Novartis Immunology Field Boasts Blockbuster DrugsCosentyx、Promacta/Revolade、Kesimpta、 XolairAndFabhaltaetc.CosentyxIt was developed by Novartis and is a targetedIL-17AMonoclonal antibody drugs, successively in2016Year3Month and2019Year4Month of approval for marketing in the United States and China, currently approved indications include psoriatic arthritis (PsA), Plaque Psoriasis (PsO), Ankylosing Spondylitis (AS) and active juvenile psoriatic arthritis (JPsA), etc.Since its approval, the sales of Cosentyx have steadily increased, reaching $2.837 billion in 2018, surpassing $4 billion in 2021 to reach $4.718 billion, hitting $4.788 billion in 2022, and achieving $4.98 billion in sales in 2023. In the third quarter of this year, sales reached $1.693 billion (Figure 6), bringing the total sales for the first nine months to $4.545 billion.Figure 6. Cosentyx Sales RevenueRevolade(Elbonin/Eltrombopag (European/Indian version) / Promacta (US version) is a small molecule thrombopoietin receptor agonist initially developed by GSK.TPO-RA), in 2014, NovartisAcquired the product through an asset swap transaction with GSK.Revolade/Promacta was successively launched in the United States in November 2008 and in China in December 2017 for the treatment of chronic immune thrombocytopenia (ITP).Revolade/Promacta global sales exceeded $1 billion in 2018, entering the blockbuster drug category, with $1.416 billion in 2019, a year-on-year increase of 21%. Global sales reached $1.738 billion in 2020, a year-on-year increase of 22.74%, and sales reached $2.016 billion in 2021, $2.088 billion in 2022, and sales in 2023...22.69Billion US dollars.Kesimpta (Ofatumab) is a CD20-targeted monoclonal antibody developed by Novartis, which was approved in 2009 for the treatment of chronic lymphocytic leukemia.Later thanIn August 2020, it was approved by the U.S. FDA as a subcutaneous injection for the treatment of adult relapsing multiple sclerosis (RMS). Subsequently, with the approval of indications in the autoimmune field,KesimptaSales volume begins to surge。2022YearKesimptaYear-on-year sales growth194%To10.92Billion US dollars,2023YearKesimptaYear-on-year sales growth99%To21.71Billion US dollars.Fabhalta （iptacopan) is a complement developed by Novartis.BFactor inhibitors, which play a proximal role in the alternative complement pathway of the immune system, comprehensively controlling red blood cells inside and outside blood vessels.(RBC) Destruction.2023Year12Month5Day,FabhaltaFirst ObtainedFDAApproved for marketing as the first oral monotherapy for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) Adult patients. In clinical trials, use FabhaltaTreatment can increase hemoglobin levels in most patients (without red blood cell transfusion, hemoglobin levels are higher than baseline).≥ 2g/dL), inAPPLY-PNH In the trial, almost all recipientsFabhalta None of the treated patients received a blood transfusion.In addition, Novartis has up to 26 immunology pipelines in clinical layout, including those in Phase 1 clinical trials.IPX643, MHV370, PIT565, Phase 2 clinical trials of iscalimab and DFV890, and Phase 3 clinical trials of remibrutinib and ianalumabetc. (Fig. 7). Figure 7. Novartis Clinical Pipeline SummaryIanalumabIt was developed by Novartis as an anti-BAFF-RFully human monoclonal antibody, targetingBCells, can be used withBCell Activation Factor Receptor (BAFF-R) combination, currently in clinical3Period, used for the treatment of Sjögren's syndrome, lupus nephritis, and systemic lupus erythematosus.Major pharmaceutical companies have heavy-hitting products in the autoimmune field. As a precaution to prevent a cliff-like drop in sales due to the expiration of key product patents, these companies are actively working on developing numerous autoimmune pipelines, offering more choices for patients.
References
1. Lutikizumab Showed Positive Results in a Phase 2 Trial of Adults with Moderate to Severe Hidradenitis Suppurativa as Program Advances to Phase 3
2. TREMFYA® (guselkumab) receives U.S. FDA approval for adults with moderately to severely active ulcerative colitis, strengthening Johnson & Johnson’s leadership in inflammatory bowel disease
3. Nipocalimab demonstrates significant clinical improvement in disease activity and IgG reduction in Phase 2 Sjögren’s disease study
4.https://assets.roche.com/f/176343/x/f7a9170178/231024_mr_q3_roche-2024_en.pdf
5. Julie Langlois et.al, Fenebrutinib, a Bruton’s tyrosine kinase inhibitor, blocks distinct human microglial signaling pathways, Journal of Neuroinflammation (2024) 21:276
6. Press Release: Dupixent approved in the US as the first-ever biologic medicine for patients with COPD
7. Press Release: Dupixent approved in the EU as the first and only medicine for young children with eosinophilic esophagitis
Pharmacodia Media Business CooperationMedia PR | News &Press ReleaseManager Zhang: 18600036371 (Same for WeChat)Click "PharmSnap" below to follow more exciting content.
The article reproduced by the "Pharmacology Bridge" WeChat Official Account is sourced from another official account platform. Its main purpose is to share relevant industry knowledge and convey the latest current information. The images and articles are owned by the original authors, and if there is any infringement, please inform us in a timely manner, and we will delete the relevant information within 24 hours.The push rules of WeChat Official Accounts have changed again. If you don't tap"Viewing"Or not set to"Star Mark", we might just dissipate in the vast sea of text~ Click here, don't miss out on the latest news from PharmaDJ!??
