BCG vaccine(Max Planck Institute For Infection Biology)

New Delhi: For more than a century, the onus of combating TB has relied upon the 20th-century breakthrough called the BCG vaccine (Bacillus Calmette–Guérin), which helps activate the immune response against the disease-causing bacterium Mycobacterium tuberculosis (Mtb). The data speaks for the effectiveness of the vaccine, which made it an integral part of various global and individual government efforts that helped save around 79 million lives (since 2000) from the deadliest infectious disease . However, being administered at birth under various elimination programs, including in India since 1985, the Global TB report 's revelation of the disease shifting burden among adults, increasing drug resistance, and a temporary blip due to the pandemic—which reversed the long-maintained downward curve both in terms of incidence rate—points to the limits in the conventional safety net and further reflects the ample scope for exploring and introducing newer innovations. Source: Global TB report 2024, WHO Moreover, as per the WHO, the existing “neonatal BCG vaccination offers partial protection for infants and young children against severe forms of TB, but it does not protect adolescents and adults, who account for the majority of TB transmission. Vaccines also offer the best chance to contain the accelerating spread of multi-drug resistant tuberculosis.” “The entire mycobacterium used in BCG is one that is related to Mycobacterium tuberculosis, but not the same. It is missing about 170 genes that Mycobacterium tuberculosis has, and this is possibly why the immunity offered tends to be very limited,” Dr Lancelot Pinto, Consultant Pulmonologist and Epidemiologist, P. D. Hinduja Hospital & Medical Research Centre, told ET Pharma. Nevertheless, beneath this cloudy landscape, there are rising signs of hope to combat the disease through a handful of new vaccines. As per the GlobalData drug pipeline database, currently, there are 15 prophylactic vaccines under different clinical development stages. Of these 15 under-trial candidates, three innovations— MTBVAC , M72/AS01E , and VPM1002—are in the Phase 3 clinical trial phase, while one candidate, GC-3107A, developed by GC Biopharma, is in the pre-registration phase, which initiates the regulatory review required for market roll-out of a product. Source: GlobalData pipeline products database Unlike the other versions, GC-3107A is a therapeutic vaccine indicated for latent or active TB patients. Among the three late-stage frontrunners, MTBVAC (Mycobacterium Tuberculosis [Live Attenuated] Vaccine) is developed by the University of Zaragoza, whose industrial partner, BioFabri—a Spanish biotech firm—overtook the clinical development in partnership with India’s Bharat Biotech. The candidate is stated to be developed from a genetically modified form of the pathogen isolated from the disease bacterium and, as per the partners, unlike BCG, it contains all the antigens present in strains that infect humans. Currently, the vaccine is being tested on over 7,000 infants in South Africa, Senegal, and Madagascar, with the BCG control arm. The second candidate, M72/AS01E, was initially developed by MNC giant GlaxoSmithKline or GSK, with the final phase of clinical development led by the Gates Medical Research Institute , supported by the Gates Foundation, and Wellcome (a healthcare charitable trust). M72/AS01E is a two-dose regimen version developed from two Mtb antigens—MTB32A and MTB39A—and in March 2024, the partners announced the initiation of Phase 3 trials in South Africa to assess the efficacy of the vaccine. Later, the candidate was also introduced at trial sites in Indonesia, Kenya, Malawi, and Zambia, with a total cohort size of 20,000. The Phase 3 trials for both of the aforementioned candidates are expected to conclude by August 2029. Lastly, VPM-1002 is an innovation from Serum Institute of India, developed by Serum Institute of India (SII), as a potential replacement for the standard BCG vaccine, aiming for improved safety and efficacy in preventing tuberculosis (TB). The candidate is in the Phase 3 trial phase, being tested in a multisite, randomized, double-blinded, placebo-controlled Phase III clinical trial among 6,940 newborn infants from Gabon, Kenya, South Africa, Tanzania, and Uganda, with the BCG control arm. The trial is supported by India’s Department of Biotechnology’s National Biopharma Mission. Several attempts by ET Pharma to obtain additional information from the Serum Institute did not elicit any response. As per the government department, the objective of this trial is to evaluate the ability of VPM-1002 to reduce infection incidence and severe disease outcomes of COVID-19 among high-risk persons of advanced age or comorbidities and high-exposure healthcare workers (HCWs). According to the WHO TB research tracker, the vaccine's Phase 3 trials are expected to conclude by October 2025. Dissecting the targeting mechanism of these under-trial candidates with the existing option, Dr. Pinto told ET Pharma, “The BCG vaccine has been shown to be effective against severe forms of TB in childhood, but its effectiveness beyond this has not been proven, and this possibly explains why, despite having a universal BCG vaccination at birth since 1985, India has not been able to eradicate the disease.” Dr. Pinto explained that the newer vaccines attempt to improve BCG in different ways: MTBVAC is live and attenuated but uses Mtb (and not bovis), with genetic modifications that render them safe. Meanwhile, VPM-1002 uses a recombinant BCG strain and has enhanced immunogenicity because of the expression of Listeriolysin-O, which allows the antigens to enter the cells and stimulate a stronger T-cell response. As per the expert, the pre-registration candidate GC-3107A of GC Biopharma has a similar mechanism as in the case of MTBVAC. Commenting on the best potential candidate to deal with the rising prevalence of TB among adults, Dr. Pinto said, “M72/AS01E is possibly one of the most promising vaccines, as the Phase 2b vaccine trial recruited adults aged 18 to 50 years with M.TB infection, and was found to be 49.7 percent efficacious at preventing TB in the 3-year follow-up period with two doses.” This demographic is possibly the most prevalent presently, and protecting them would be the most important priority in reducing the prevalence of the disease. This vaccine is also closest to completing its Phase 3 trials and is therefore likely to be the most relevant presently, he added. In contrast to this, Anaelle Tannen, Infectious Disease Analyst at GlobalData, expects BioFabri’s MTBVAC will provide an alternative way to treat the disease and has been shown to be safe and effective thus far in clinical trials. Notably, the GSK candidate has also received endorsement from the WHO, and the UN subsidy has said that the vaccine results (Phase 2b trial) are “unprecedented in decades of TB vaccine research” in terms of clinical significance and strength of evidence, and constitute an important scientific breakthrough.” Moreover, the body has also urged the “tuberculosis vaccine community to discuss future development options for this vaccine candidate.” Sharing a WHO estimate, Alexander Schmidt, Interim Head of Development and Chief Medical Officer, Gates Medical Research Institute, told ET Pharma that, “Their vaccine could save 8.5 million lives, prevent 76 million new TB cases, and save $41.5 billion for TB-affected households.” Commenting on the post-trial plans, including possible regional launches, Schmidt replied that, “We are working with our trial partners, as well as multilateral, regional, and country partners, to understand the potential demand for the vaccine so that we can build an end-to-end plan to ensure long-term sustainable access in communities of high disease burden, should the trial be successful.” For India, both the TB incidence rate and mortality count have been on the downturn, but considering the changing demographic profile of TB, the policymakers are exploring options like “BCG revaccination in adults,” and in January 2024, the Ministry of Health and Family Welfare, in collaboration with the Indian Council of Medical Research (ICMR), launched the "Adult BCG Vaccination Study" to explore the vaccine's effectiveness among high-risk individuals. Last year, Bharat Biotech announced its plans to test its candidate MTBVAC among Indian adults, and a company release states that the trials “are planned to start in 2025 to evaluate the safety and immunogenicity of MTBVAC among adults in India.” Making the announcement, Dr. Krishna Ella, Executive Chairman, Bharat Biotech, had said that, “Our goal to develop TB vaccines to prevent disease in adults and adolescents has taken a big step today. We are honoured to partner with BioFabri in this noble effort to reinvent TB vaccines.” As per the latest available update, in October 2024, the Indian drug regulator, CDSCO, asked the Hyderabad-based vaccine player to share its trial protocols. Over the inclusion of other under-trial candidates under India’s Universal Immunisation Program or as a booster dose option among already vaccinated individuals, Dr. Pinto suggested analysing the cost-effectiveness of each candidate. One of the Phase 3 candidates, M72/AS01E, if cleared by the regulatory review, is estimated to be priced at around $2.5 (around ₹214) per dose and is a double-dose regimen, whereas the available single-shot BCG brands, such as one from SII, are priced at around ₹60 for a 40 ml vial. A study comparing the financial cost of M72/AS01E with BCG found that initiating BCG revaccination in India could incur an average annual cost of around $23 million, whereas the M72/AS01E vaccine is projected to cost around $190 million per year. The emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains has made the challenging TB terrain more bumpy, and compounding this, Dr. Pinto expects “Mtb strains are likely to become resistant to newer drugs such as Bedaquiline and Delamanid (the current line of treatment) as their use increases, and unless the new drug pipeline matches such resistance, we are likely to face serious challenges with treating the disease in the future.” However, as of now, the under-trial vaccines are viewed as the best option to safeguard the population from a preventable challenge. Medical innovation takes years to reach fruition and requires a heavy purse to sustain and survive that period, but with bipartisan consensus, the world has made significant strides towards the elimination of a condition where the fate of around. By Abhijeet Singh ,

TREMFYA® is the only IL-23i to demonstrate clinical remission and endoscopic response, both at one year, with a fully subcutaneous induction regimen Supported by data from the GALAXI study, TREMFYA® is the only IL-23i to show superiority versus STELARA® in all pooled endoscopic endpoints within a double-blinded registrational trial TREMFYA® approval in Crohn's disease builds upon recent ulcerative colitis FDA approval, marking the fourth indication for this dual-acting IL-23i in the U.S. HORSHAM, Pa., March 20, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced that the U.S. Food and Drug Administration (FDA) has approved TREMFYA® (guselkumab), the first and only IL-23 inhibitor offering both subcutaneous (SC) and intravenous (IV) induction options, for the treatment of adults with moderately to severely active Crohn's disease (CD), a chronic inflammatory condition of the gastrointestinal tract.1 This milestone builds upon the FDA approval of TREMFYA® in moderately to severely active ulcerative colitis (UC), one of two main forms of inflammatory bowel disease (IBD),2 which impacts the lives of nearly three million Americans.3 TREMFYA® is the first and only approved fully-human, dual-acting monoclonal antibody that blocks IL-23 while also binding to CD64, a receptor on cells that produce IL-23. IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells that is known to be a driver of immune-mediated diseases including CD.4,5,6,7,8 "Despite the progress in the management of Crohn's disease, many patients experience debilitating symptoms and are in need of new treatment options," said Remo Panaccione, MD, FRCPC, Professor of Medicine and the Director of the Inflammatory Bowel Disease Unit at the University of Calgary and lead investigator of the Phase 3 GRAVITI study. "The approval of TREMFYA offers an IL-23 inhibitor that has shown robust rates of endoscopic remission with both subcutaneous and intravenous induction regimens. Importantly, the fully subcutaneous regimen offers choice and flexibility for patients and providers that have not been available before." This approval is supported by results from multiple rigorous Phase 3 trials evaluating more than 1,300 patients with moderately to severely active CD who failed or were intolerant to conventional therapy (i.e. corticosteroids or immunomodulators) or biologics.6 The GRAVITI study evaluated TREMFYA® SC induction and maintenance therapy versus placebo. Data from the GALAXI clinical program showed TREMFYA® was superior to STELARA® in all pooled endoscopic endpoints, the only IL-23 inhibitor to achieve this in a double-blinded registrational program. The comprehensive results from these Phase 3 studies demonstrated the robust efficacy of SC or IV TREMFYA® in achieving clinical and endoscopic endpoints. Highlights from these pivotal studies showed:6 Week 12 Results GRAVITI GALAXI 2 GALAXI 3 TREMFYA® 400 mg SCinduction at Weeks 0, 4and 8 vs. placebo TREMFYA® 200 mg IVinduction at Weeks 0, 4and 8 vs. placebo TREMFYA® 200 mg IVinduction at Weeks 0, 4and 8 vs. placebo Clinical remission 56% vs. 22% (p<0.001) 47% vs. 20% (p<0.001) 47% vs. 15% (p<0.001) Endoscopic response 34% vs. 15% (p<0.001) 36% vs. 9% (p<0.001) 34% vs. 13% (p<0.001) Week 48 Results GRAVITI TREMFYA® 100 mg SC maintenanceq8w starting at Week 16 vs. placebo TREMFYA® 200 mg SC maintenanceq4w starting at Week 12 vs. placebo Clinical remission 59% vs. 17% 65% vs. 17% Endoscopic response 39% vs. 5% 48% vs. 5% Endoscopic remission 31% vs. 6% 40% vs. 6% Deep remission (clinical & endoscopicremission)9 26% vs. 4% 34% vs. 4% "TREMFYA is the first and only IL-23 inhibitor that offers a fully subcutaneous treatment option for moderately to severely active Crohn's disease. With the approval of TREMFYA, it is now possible to achieve meaningful improvements in clinical and endoscopic outcomes with the flexibility of self-administration from the start," said Chris Gasink, MD, Vice President, Medical Affairs, Gastroenterology & Autoantibody, Johnson & Johnson Innovative Medicine. "TREMFYA provides people living with Crohn's disease and their healthcare providers a new treatment option that is supported by data from multiple Phase 3 studies, including pooled analyses showing statistical superiority versus STELARA across four endoscopic or combined clinical and endoscopic endpoints." TREMFYA® dosing in the treatment of moderately to severely active CD:6 The recommended SC induction dosage is 400 mg (given as two consecutive injections of 200 mg each, dispensed in one Induction Pack) at Weeks 0, 4 and 8. TREMFYA® is also available in a 200 mg prefilled syringe. For the IV induction option, 200 mg IV infusions are administered at Weeks 0, 4 and 8. Recommended maintenance dosage is 100 mg administered by SC injection at Week 16, and every 8 weeks thereafter, or 200 mg administered by SC injection at Week 12, and every 4 weeks thereafter. Healthcare providers are instructed to use the lowest effective recommended dosage to maintain therapeutic response. Johnson & Johnson is committed to supporting access to all its treatments, including offering a patient support program called TREMFYA® withMe. For commercially insured patients, adults who are prescribed TREMFYA® for CD may be eligible to receive their first induction treatment in as little as 24 hours through TREMFYA® withMe. This approval marks the fourth indication for TREMFYA® in the U.S., following moderate-to-severe plaque psoriasis in July 2017, active psoriatic arthritis in July 2020 and moderately to severely active UC in September 2024,6 underscoring Johnson & Johnson's long-standing legacy in innovation and commitment to patients living with chronic immune-mediated diseases, including IBD. In November 2024, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the FDA seeking approval of a SC induction regimen of TREMFYA® for the treatment of adults with moderately to severely active UC, based on results of the Phase 3 ASTRO study. Editor's Notes: a) CD64+ cells are the predominant source of IL-23 in CD. Cells not expressing CD64 may also contribute to IL-23 production but to a lesser extent.1,3b) "Only" based on approved selective IL-23 inhibitors for moderately to severely active CD as of March 2025.6,7,8c) Based on in vitro studies in an inflammatory monocyte model.4 d) Moderately to severely active CD was defined as a Crohn's Disease Activity Index (CDAI) score of ≥220 and a Simple Endoscopic Score for Crohn's Disease (SES-CD) of ≥6 (or ≥4 for subjects with isolated ileal disease).6e) Clinical remission was defined as a CDAI score of <150.,6f) Endoscopic response is defined as >50% improvement from baseline in SES-CD score.6g) Endoscopic remission was defined as an SES-CD score ≤4 and at least a 2-point reduction from baseline and no subscore greater than 1 in any individual component.6h) q4w is defined as every four weeks.6i) q8w is defined as every eight weeks.6j) Dr. Panaccione is a paid consultant for Johnson & Johnson. He has not been compensated for any media work. ABOUT THE GRAVITI STUDY (NCT05197049) GRAVITI is a randomized, double-blind, placebo-controlled Phase 3 study to evaluate guselkumab SC induction therapy (400 mg at Weeks 0, 4, and 8) in patients with moderately to severely active Crohn's disease who experienced an inadequate response or failed to tolerate conventional therapy (i.e., corticosteroids or immunomodulators) or biologic therapy (TNF antagonists or vedolizumab).10 Patients received guselkumab 400 mg SC q4w (x3) followed by guselkumab 200 mg SC q4w; or guselkumab 400 mg SC q4w (x3) followed by guselkumab 100 mg SC q8w; or placebo. The maintenance doses in GRAVITI (200 mg SC q4w and 100 mg SC q8w) are the same as those evaluated in the Phase 3 GALAXI 2 and GALAXI 3 studies that evaluated the efficacy and safety of IV induction followed by SC maintenance therapy in patients with moderate to severely active Crohn's disease. Similar to GALAXI, GRAVITI employed a treat-through design, in which patients were randomized to guselkumab at Week 0 and remained on that regimen throughout the study, regardless of clinical response status at the end of induction. Participants randomized to placebo were able to receive guselkumab (400 mg SC q4w x3 ➔ 100 mg SC q8w) if rescue criteria were met at Week 16.10 ABOUT THE GALAXI PROGRAM (NCT03466411) GALAXI is a randomized, double-blind, placebo-controlled, active-controlled (ustekinumab), global, multicenter Phase 2/3 program designed to evaluate the efficacy and safety of guselkumab in participants with moderately to severely active Crohn's disease with inadequate response/intolerance to conventional therapies (corticosteroids or immunomodulators) and/or biologics (TNF antagonists or vedolizumab).11 GALAXI includes a Phase 2 dose-ranging study (GALAXI 1) and two independent, identically designed confirmatory Phase 3 studies (GALAXI 2 and 3).11 Each GALAXI study employed a treat-through design in which participants remained on the treatment to which they were initially randomized and includes a long-term extension study that will assess clinical, endoscopic, and safety outcomes with guselkumab through a total of five years. Patients received guselkumab 200 mg intravenous induction at Weeks 0, 4 and 8 followed by guselkumab 200 mg subcutaneous maintenance every 4 weeks; or guselkumab 200 mg intravenous induction at Weeks 0, 4 and 8, followed by guselkumab 100 mg subcutaneous maintenance every 8 weeks; or a biologic active control; or placebo. Participants randomized to placebo were able to receive ustekinumab if clinical response was not met at Week 12. Of the 873 individuals pooled across the GALAXI 2 & 3 dataset, 456 (52 percent) had prior history of inadequate response to biologics, 365 (42 percent) were biologic-naïve and 52 (6 percent) were biologic experienced without documented inadequate response or intolerance.12 The GALAXI 2 and GALAXI 3 studies were the first-ever double-blind registrational head-to-head clinical trials to demonstrate superiority versus ustekinumab in Crohn's disease, showing guselkumab was superior to ustekinumab in all endoscopic-based endpoints when analyzed with pooled data. ABOUT CROHN'S DISEASE Crohn's disease is one of the two main forms of inflammatory bowel disease, which affects an estimated three million Americans.3 Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract with no known cause, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition, diet, or other environmental factors.1 Symptoms of Crohn's disease can vary, but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss, and fever. Currently no cure is available for Crohn's disease.3 ABOUT TREMFYA® (guselkumab) Developed by Johnson & Johnson, TREMFYA® is the first approved fully-human, dual-acting monoclonal antibody designed to neutralize inflammation at the cellular source by blocking IL-23 and binding to CD64 (a receptor on cells that produce IL-23). Findings for dual-acting are limited to in vitro studies that demonstrate guselkumab binds to CD64, which is expressed on the surface of IL-23 producing cells in an inflammatory monocyte model. The clinical significance of this finding is not known. TREMFYA® is a prescription medicine approved in the U.S. to treat: adults with moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light). adults with active psoriatic arthritis. adults with moderately to severely active ulcerative colitis. adults with moderately to severely active Crohn's disease. TREMFYA® is approved in Europe, Canada, Japan, and a number of other countries for the treatment of adults with moderate-to-severe plaque psoriasis and for the treatment of adults with active psoriatic arthritis. Johnson & Johnson maintains exclusive worldwide marketing rights to TREMFYA®. For more information, visit: www.tremfya.com. IMPORTANT SAFETY INFORMATIONWhat is the most important information I should know about TREMFYA®?TREMFYA® is a prescription medicine that may cause serious side effects, including: Serious Allergic Reactions. Stop using TREMFYA® and get emergency medical help right away if you develop any of the following symptoms of a serious allergic reaction: ο fainting, dizziness, feeling lightheaded (low blood pressure) ο swelling of your face, eyelids, lips, mouth, tongue or throat ο trouble breathing or throat tightness ο chest tightness ο skin rash, hives ο itching Infections. TREMFYA® may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with TREMFYA® and may treat you for TB before you begin treatment with TREMFYA® if you have a history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB during and after treatment with TREMFYA®. Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including: ο fever, sweats, or chills ο muscle aches ο weight loss ο cough ο warm, red, or painful skin or sores on your body different from your psoriasis ο diarrhea or stomach pain ο shortness of breath ο blood in your phlegm (mucus) ο burning when you urinate or urinating more often than normal Liver problems. With the treatment of Crohn's disease or ulcerative colitis, your healthcare provider will do blood tests to check your liver before and during treatment with TREMFYA®. Your healthcare provider may stop treatment with TREMFYA® if you develop liver problems. Tell your healthcare provider right away if you notice any of the following symptoms: ο unexplained rash ο vomiting ο tiredness (fatigue) ο yellowing of the skin or the whites of your eyes ο nausea ο stomach pain (abdominal) ο loss of appetite ο dark urine Do not use TREMFYA® if you have had a serious allergic reaction to guselkumab or any of the ingredients in TREMFYA®. Before using TREMFYA®, tell your healthcare provider about all of your medical conditions, including if you: have any of the conditions or symptoms listed in the section "What is the most important information I should know about TREMFYA®?" have an infection that does not go away or that keeps coming back. have TB or have been in close contact with someone with TB. have recently received or are scheduled to receive an immunization (vaccine). You should avoid receiving live vaccines during treatment with TREMFYA®. are pregnant or plan to become pregnant. It is not known if TREMFYA® can harm your unborn baby.Pregnancy Registry: If you become pregnant during treatment with TREMFYA®, talk to your healthcare provider about registering in the pregnancy exposure registry for TREMFYA®. You can enroll by visiting www.mothertobaby.org/ongoing-study/tremfya-guselkumab, by calling 1-877-311-8972, or emailing MotherToBaby@health.ucsd.edu. The purpose of this registry is to collect information about the safety of TREMFYA® during pregnancy. are breastfeeding or plan to breastfeed. It is not known if TREMFYA® passes into your breast milk. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What are the possible side effects of TREMFYA®?TREMFYA® may cause serious side effects. See "What is the most important information I should know about TREMFYA®?" The most common side effects of TREMFYA® include: respiratory tract infections, headache, injection site reactions, joint pain (arthralgia), diarrhea, stomach flu (gastroenteritis), fungal skin infections, herpes simplex infections, stomach pain, and bronchitis. These are not all the possible side effects of TREMFYA®. Call your doctor for medical advice about side effects. Use TREMFYA® exactly as your healthcare provider tells you to use it. Please read the full Prescribing Information, including Medication Guide, for TREMFYA® and discuss any questions that you have with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Dosage Forms and Strengths: TREMFYA® is available as 100 mg/mL and 200 mg/2mL for subcutaneous injection and as a 200 mg/20 mL (10 mg/mL) single dose vial for intravenous infusion. ABOUT STELARA® (ustekinumab) STELARA® (ustekinumab), a human interleukin (IL)-12 and IL-23 antagonist, is a prescription medicine approved in the United States to treat.13 adults and children 6 years and older with moderate to severe psoriasis who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light alone or with pills). adults and children 6 years and older with active psoriatic arthritis. adults 18 years and older with moderately to severely active Crohn's disease. adults 18 years and older with moderately to severely active ulcerative colitis. The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to STELARA®. IMPORTANT SAFETY INFORMATION STELARA® is a prescription medicine that affects your immune system. STELARA® can increase your chance of having serious side effects including: Serious Infections STELARA® may lower your ability to fight infections and may increase your risk of infections. While taking STELARA®, some people have serious infections, which may require hospitalization, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses. Your doctor should check you for TB before starting STELARA® and watch you closely for signs and symptoms of TB during treatment with STELARA®. If your doctor feels that you are at risk for TB, you may be treated for TB before and during treatment with STELARA®. You should not start taking STELARA® if you have any kind of infection unless your doctor says it is okay. Before starting STELARA®, tell your doctor if you: think you have an infection or have symptoms of an infection such as: fever, sweats, or chills muscle aches cough shortness of breath blood in phlegm weight loss warm, red, or painful skin or sores on your body diarrhea or stomach pain burning when you urinate or urinate more often than normal feel very tired fever, sweats, or chills muscle aches cough shortness of breath blood in phlegm weight loss warm, red, or painful skin or sores on your body diarrhea or stomach pain burning when you urinate or urinate more often than normal feel very tired are being treated for an infection or have any open cuts. get a lot of infections or have infections that keep coming back. have TB, or have been in close contact with someone with TB. After starting STELARA®, call your doctor right away if you have any symptoms of an infection (see above). These may be signs of infections such as chest infections, or skin infections or shingles that could have serious complications. STELARA® can make you more likely to get infections or make an infection that you have worse. People who have a genetic problem where the body does not make any of the proteins interleukin 12 (IL-12) and interleukin 23 (IL-23) are at a higher risk for certain serious infections that can spread throughout the body and cause death. People who take STELARA® may also be more likely to get these infections. Cancers STELARA® may decrease the activity of your immune system and increase your risk for certain types of cancer. Tell your doctor if you have ever had any type of cancer. Some people who had risk factors for skin cancer developed certain types of skin cancers while receiving STELARA®. Tell your doctor if you have any new skin growths. Posterior Reversible Encephalopathy Syndrome (PRES) PRES is a rare condition that affects the brain and can cause death. The cause of PRES is not known. If PRES is found early and treated, most people recover. Tell your doctor right away if you have any new or worsening medical problems including: headache, seizures, confusion, and vision problems. Serious Allergic Reactions Serious allergic reactions can occur. Stop using STELARA® and get medical help right away if you have any symptoms of a serious allergic reaction such as: feeling faint, swelling of your face, eyelids, tongue, or throat, chest tightness, or skin rash. Lung Inflammation Cases of lung inflammation have happened in some people who receive STELARA® and may be serious. These lung problems may need to be treated in a hospital. Tell your doctor right away if you develop shortness of breath or a cough that doesn't go away during treatment with STELARA®. Before receiving STELARA®, tell your doctor about all of your medical conditions, including if you: have any of the conditions or symptoms listed above for serious infections, cancers, or PRES. ever had an allergic reaction to STELARA® or any of its ingredients. Ask your doctor if you are not sure. are allergic to latex. The needle cover on the prefilled syringe contains latex. have recently received or are scheduled to receive an immunization (vaccine). People who take STELARA® should not receive live vaccines. Tell your doctor if anyone in your house needs a live vaccine. The viruses used in some types of live vaccines can spread to people with a weakened immune system, and can cause serious problems. You should not receive the BCG vaccine during the one year before receiving STELARA® or one year after you stop receiving STELARA®. have any new or changing lesions within psoriasis areas or on normal skin. are receiving or have received allergy shots, especially for serious allergic reactions. receive or have received phototherapy for your psoriasis. are pregnant or plan to become pregnant. It is not known if STELARA® can harm your unborn baby. You and your doctor should decide if you will receive STELARA®. received STELARA® while you were pregnant. It is important that you tell your baby's healthcare provider before any vaccinations are given to your baby. are breastfeeding or plan to breastfeed. STELARA® can pass into your breast milk. talk to your doctor about the best way to feed your baby if you receive STELARA®. Tell your doctor about all the medicines you take, including prescription and over-the counter medicines, vitamins, and herbal supplements. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. When prescribed STELARA®: Use STELARA® exactly as your doctor tells you to. STELARA® is intended for use under the guidance and supervision of your doctor. In children 6 years and older, it is recommended that STELARA® be administered by a healthcare provider. If your doctor decides that you or a caregiver may give your injections of STELARA® at home, you should receive training on the right way to prepare and inject STELARA®. Your doctor will determine the right dose of STELARA® for you, the amount for each injection, and how often you should receive it. Do not try to inject STELARA® yourself until you or your caregiver have been shown how to inject STELARA® by your doctor or nurse. Common side effects of STELARA® include: nasal congestion, sore throat, and runny nose, upper respiratory infections, fever, headache, tiredness, itching, nausea and vomiting, redness at the injection site, vaginal yeast infections, urinary tract infections, sinus infection, bronchitis, diarrhea, stomach pain, and joint pain. These are not all of the possible side effects with STELARA®. Tell your doctor about any side effect that you experience. Ask your doctor or pharmacist for more information. Please click to read the full Prescribing Information and Medication Guide for STELARA® and discuss any questions you have with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit https://www.fda.gov/medwatch or call 1-800-FDA-1088. ABOUT JOHNSON & JOHNSON At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com. Follow us at @JNJInnovMed. Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC, Janssen Biotech, Inc., and Janssen-Cilag International NV are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding TREMFYA®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC, Janssen Biotech, Inc., Janssen-Cilag International NV and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC, Janssen Biotech, Inc., Janssen-Cilag International NV nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. 1 Crohn's & Colitis Foundation. What is Crohn's disease? Available at: https://www.crohnscolitisfoundation.org/what-is-crohns-disease/causes. Accessed February 2025.2 Crohn's & Colitis Foundation. What is Crohn's disease? Available at: https://www.crohnscolitisfoundation.org/what-is-crohns-disease/causes. Accessed February 2025.3 Crohn's & Colitis Foundation. Overview of Crohn's disease. Available at: https://www.crohnscolitisfoundation.org/what-is-crohns-disease/overview. Accessed March 2025.4 Atreya R, Abreu MT, Krueger JG, et al. Guselkumab, an IL-23p19 subunit-specific monoclonal antibody, binds CD64+ myeloid cells and potentially neutralizes IL-23 produced from the same cells. Poster presented at: 18th Congress of the European Crohn's and Colitis Organization (ECCO); March 1-4, 2023; Copenhagen, Denmark. Poster P504.5 Kreuger JG, Eyerich K, Kuchroo VK. Il-23 past, present, and future: a roadmap to advancing IL-23 science and therapy. Front Immunol. 2024; 15:1331217. doi:10.3389/fimmu.2024.1331217.6 TREMFYA® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.7 Skyrizi® [Prescribing Information]. North Chicago, IL: AbbVie, Inc.8 Omvoh™ [Prescribing Information]. Indianapolis, IN: Eli Lilly and Company.9 Panaccione, R, et al. Efficacy and Safety of Subcutaneous Guselkumab Induction Therapy in Patients With Moderately to Severely Active Crohn's Disease: Results Through Week 48 From the Phase 3 GRAVITI Study. Oral presentation (OP72) at American College of Gastroenterology (ACG) 2024.10 National Institutes of Health: Clinicaltrials.gov. A study of guselkumab subcutaneous therapy in participants with moderately to severely active Crohn's disease (GRAVITI). Identifier: NCT05197049. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT05197049. Accessed February 2025.11 National Institutes of Health: Clinicaltrials.gov. A study of the efficacy and safety of guselkumab in participants with moderately to severely active Crohn's disease (GALAXI). Identifier: NCT03466411. Available at: https://clinicaltrials.gov/study/NCT03466411. Accessed February 2025.12 Danese S, et al. Week 48 efficacy of guselkumab and ustekinumab in Crohn's disease based on prior response/exposure to biologic therapy: Results from the GALAXI 2 & 3 Phase 3 Studies. Poster presentation (Abstract MP672) at United European Gastroenterology Week (UEGW) 2024. October 2024.13 STELARA® Prescribing information. Available at: https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/STELARA-pi.pdf Accessed March 2025. View original content to download multimedia:https://www.prnewswire.com/news-releases/us-fda-approves-tremfya-guselkumab-the-first-and-only-il-23-inhibitor-offering-both-subcutaneous-and-intravenous-induction-options-for-adult-patients-with-moderately-to-severely-active-crohns-disease-302407565.html SOURCE Johnson & Johnson