Latest news with #BillMezzanotte
News.com.au
13 hours ago
- Business
- News.com.au
Biocurious: CSL's R&D chief says drug development is like falling in love
CSL's hereditary angioedema prophylactic Andembry is one of only a handful of FDA-approved, Australian-developed drugs Andembry reflects CSL's R&D approach of sticking with 'adjacent' competencies CSL spends around $2.3 billion a year on R&D, but it's still outgunned by rivals and needs to play smart CSL (ASX:CSL) global head of research and development Bill Mezzanotte likens drug development to falling in love. 'If you don't put your whole heart into it, it won't work,' the Pennsylvania-based Mezzanotte told Stockhead. 'But when you do, you are at risk of having your heart broken and that sometimes happens.' The blood plasma giant certainly has had its share of heartbreak along the way, including a failed heart attack mega trial. But as a 'hopeless romantic', Mezzanotte remains confident about the life-saving potential of the company's circa US$1.5 billion ($2.3 billion) a year R&D program. Justifying this optimism, CSL last week won US Food and Drug Administration (FDA) assent for Andembry (garadacimab), a new treatment for the severe swelling condition hereditary angioedema (HAE). In commercial terms, it's the most significant win in years for the $116 billion market cap behemoth. Rare local drug success for rare disease Developed over close to two decades, Andembry is one of only a handful of Australian-developed drugs to be approved by the FDA. It's also the first non-plasma derived monoclonal antibody to be discovered and developed entirely by CSL. Monoclonal antibodies are lab-engineered proteins that bind to a specific target such as a cancer cell or a virus. Because they're not produced from painstakingly collected blood, these remedies have much more attractive margins. Fittingly, CSL's new facility at Broadmeadows in northern Melbourne will make Andembry. Regulators in Europe, the UK, Japan, Switzerland, the United Arab Emirates and locally already had approved Andembry. But to re-phrase Paul Keating, if you are not approved in the US – the world's biggest reimbursed drug market – you are only camping out. Same but very different Andembry is intended as a powerful prophylactic for HAE, which affects about one in every 50,000 people. The disease can cause fatal swelling throat swelling. Andembry stemmed from an antibody 'library' of potential targets which CSL in licensed from the Nasdaq-listed Dyax Corp (later acquired by Shire Pharmaceuticals). CSL discovered garadacimab on the 'bookshelves', along with some other molecules. From that base, CSL did all the research and clinical development, including a 64-patient global trial dubbed Vanguard. 'We took the lead very early,' Mezzanotte says. 'We bought it all the way from research to product development.' CSL's HAE armamentum consists of the injected Haegarda and the infused Berinert (for use during attacks). Haegarda requires twice-weekly injections, while Andembry is administered monthly via a 'patient friendly' auto injector. Mezzanotte says Andembry is 'completely different' to Haegarda. Haegarda is a plasma-derived version of the C1 esterase inhibitor, which HAE patients lack. With a more 'upstream' action, Andembry targets an associate pathway called factor XIIa. 'Both are effective but effective in different ways,' Mezzanotte says, adding that Andembry is 'darned effective' with low side effects. The Vanguard trial showed Andembry reduced the median number of HAE attacks by more than 99% compared to placebo. Blockbuster potential But won't Andembry simply cannibalise Haegarda (and Berinert) revenue? Haegarda chalked up US$491 million of sales in the 2023-24 year, with Berinert contributing US$242 million. Mezzanotte says patients may prefer C1 inhibitors 'because they may do a little more than necessary'. Haegarda works well for pregnant women and it possibly is better for more severe attacks. 'Scientifically they live well together,' he says. But management hopes Andembry will steal plenty of share from Takeda's Takhzyro, the market-leading HAE drug turning over US$3 billion but also requiring twice-weekly injections. Bell Potter analyst Thomas Wakim dubs Andembry 'CSL's most commercially attractive near-term new product.' His peer at Wilsons, Dr Shane Storey estimates Andembry will achieve peak annual sales of US$600 million within five years. In the pipeline Andembry exemplifies CSL's R&D approach of not straying too far from what it's good at, whilst not being afraid to disrupt its own products. 'I'm a big believer in adjacency – utilising our plasma platform – or sticking to an area we know like HAE and disrupting ourselves,' Mezzanotte says. 'When we get too far away from our base of operations it gets a little tricky for us.' CSL's annual R&D manifesto outlines a dense agenda of advanced and nascent programs across its Behring (core plasma and specialty) and Seqirus (flu vaccine) arms. An adjuvanted trivalent cell-based flu vaccine – which includes three flu strains to be more effective – is the most advanced. The program is in phase III and may not need more data to win approval. CSL is also trialling CSL300 (clazakizumab) for patients on dialysis for end-stage kidney disease (to reduce inflammation and heart attacks). CSL inlicensed clazakizumab from another company that had tried the drug for kidney transplants without success. Vifor? I'll tell you Investors periodically have criticised CSL for its $18 billion, seemingly left-field acquisition of the Swiss kidney health and iron deficiency group, Vifor. One of CSL's stated reasons for the purchase was to expand its R&D pipeline. 'Vifor gave us an insight into kidney disease, which allowed us to use a drug we had ,' Mezzanotte says. 'It helps us to be efficient with a great chance of success.' CSL's global head of research and development Bill Mezzanotte. Pic: supplied Checking out of Heartbreak Hotel In February last year CSL experienced heartbreak – literally and figuratively – with the failure of its drug program, CSL-112, to prevent secondary heart attacks via cholesterol-reducing mechanisms. The company's 18,000 patient phase III trial failed the primary endpoint. The therapy showed the desired activity, but just not enough. Mezzanotte says the candidate had passed futility analysis, which – as the name suggests – appraises whether continuing a program makes sense. Mezzanotte says CSL took the conscious risk of eschewing a smaller intermediary trial. 'It was a particularly tough choice, a smaller trial would only have led to the bigger trial,' he says. 'We decided the most cost efficient was to go straight to the big trial but it was a risky approach and we failed.' He says the lesson of such setbacks is to 'fail well'. CSL-112 has gone back to the labs for researchers to have another look-see – but it won't be subject to another big-ticket trial. AI speeds up the 'unsexy' drudge work Mezzanotte says while AI is still immature, it could expedite early-stage drug discovery by enabling programs to skip early-stage animal modelling and to go directly to human studies. 'In theory it should improve speed and the probability of success, but we are in the infancy of using that,' he says. 'Automation has improved our productivity, but I'm hoping AI can bridge the gap with all the big laboratory work we can't afford to do. 'We haven't seen the tangible benefit yet, but we see the promise of it.' He says while AI advocates focus on the 'sexy' research side, the technology is helpful for prosaic tasks such as preparing regulatory and safety reports. 'We create a lot of documents in R&D,' Mezzanotte says. 'We used to send it by trailer, now we email it.' Getting bang for 2.3 billion bucks CSL targets an R&D spend of 10-11% revenue, equating to the $2.3 billion at present. While this sounds capacious, rivals are spending up to US$5 billion annually. Given that, the company needs to glean maximum efficiencies from its global complement of 2000 R&D staff, about one-third of which are in Australia. 'We pick and choose carefully,' Mezzanotte says. 'We can't build huge research palaces and we try keep lean and use partners whenever we can to extend our reach.' Having held senior roles at Boehringer Ingelheim and Astrazeneca, Mezzanotte says commerciality should not be a 'four letter word' in R&D. 'We look for areas of unmet need and rational targets to work on,' he says. 'There is plenty of commercial input early on, but the first few years of Andembry all about the science.' Mezzanotte says through 'great successes and some disappointments', investors have long supported CSL's R&D endeavours. 'I hope shows them the power of R&D and what we can do at CSL.'
Malaysian Reserve
17-06-2025
- Health
- Malaysian Reserve
U.S. Food and Drug Administration Approves CSL's ANDEMBRY® (garadacimab-gxii), the Only Prophylactic Hereditary Angioedema (HAE) Treatment Targeting Factor XIIa with Once-Monthly Dosing for All Patien
ANDEMBRY inhibits the top of the HAE cascade by targeting factor XIIa and provides sustained protection from attacks Once-monthly dosing reduced HAE attacks by a median of more than 99 percent and a least squares mean of 89.2 percent, compared to placebo ANDEMBRY approval expands CSL's HAE franchise and underscores the company's legacy of delivering transformational innovations to the HAE community for over four decades KING OF PRUSSIA, Pa., June 16, 2025 /PRNewswire/ — Global biotechnology leader CSL (ASX:CSL; USOTC:CSLLY) today announced the U.S. Food and Drug Administration (FDA) approved ANDEMBRY® (garadacimab-gxii), the only treatment targeting factor XIIa for prophylactic use to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. By targeting factor XIIa, a plasma protein that plays a key role in attacks of swelling in people with HAE, ANDEMBRY inhibits the top of the HAE cascade to prevent HAE attacks. ANDEMBRY, the only treatment to offer once-monthly dosing from the start for all patients, is a subcutaneous self-injection delivered in 15 seconds or less via an autoinjector with a citrate-free formula. HAE is a rare, chronic, and potentially life-threatening genetic disorder characterized by recurrent and unpredictable attacks of angioedema. Attacks of HAE are often painful and can affect multiple sites of the body, including the abdomen, larynx, face, and extremities. HAE occurs in about 1 in 50,000 people of any ethnic group. 'ANDEMBRY, the first monoclonal antibody discovered and developed entirely by CSL, offers people living with this life-threatening condition long-term control over their disease along with a convenient administration method,' said Bill Mezzanotte, MD, Executive Vice President, Head of R&D, CSL. 'ANDEMBRY underscores our long-standing and enduring commitment to better the lives of the patients we serve, including those suffering with HAE. I'd like to thank all the physicians, patients and my colleagues who contributed to this exciting milestone for HAE patients and CSL.' The approval is supported by data from the pivotal placebo-controlled Phase 3 VANGUARD trial evaluating the efficacy and safety of ANDEMBRY. The pivotal study (The Lancet, April 2023) demonstrated that treatment with ANDEMBRY: Led to 62 percent of ANDEMBRY-treated patients remaining attack-free throughout the treatment period. Reduced HAE attacks by a median of more than 99 percent and a least squares mean of 89.2 percent, compared to placebo. Achieved more than 99 percent median reduction and an 88 percent mean reduction in HAE attacks requiring on-demand therapy, compared to placebo. Attained more than 99 percent median reduction and a 90 percent mean reduction in moderate or severe attacks, compared to placebo. The most common adverse reactions in the pivotal trial (incidence ≥7%) are nasopharyngitis and abdominal pain. A published interim analysis (Allergy, Oct 2024) of the ongoing open-label extension study (median ANDEMBRY exposure of 13.8 months) showed that ANDEMBRY has a favorable long-term safety profile and provides sustained reductions in HAE attacks. In the pivotal trial and the open-label extension study, injection-site reactions (e.g., injection-site bruising, injection-site erythema, injection-site hematoma, injection-site pruritus, injection-site urticaria) were reported in 23 (14%) patients. 'We've made significant progress in treating hereditary angioedema, yet many patients still experience painful and sometimes life-threatening HAE attacks and require frequent injections to manage them,' said Dr. Tim Craig, Professor of Medicine, Pediatrics and Biomedical Sciences at Penn State University. 'We now have a new option to manage this condition through a new target, as it allows us for the first time to inhibit the top of the HAE cascade by targeting factor XIIa.' 'ANDEMBRY, a novel once-monthly subcutaneous treatment that inhibits factor XIIa, is a welcome addition to the HAE treatment landscape,' said Anthony J. Castaldo, CEO and Chairman of the Board, US HAE Association and HAE International. 'People with HAE now have another choice for lessening the burden associated with this lifelong condition and realizing the community's shared goal of experiencing life to the fullest.' This regulatory approval for ANDEMBRY is another crucial step in building toward the global availability of ANDEMBRY, which was recently approved in Australia, the United Kingdon (UK), the European Union (EU), Japan, Switzerland, and United Arab Emirates. CSL Behring will launch ANDEMBRY commercially immediately, with availability before the end of June. Healthcare professionals and patients interested in learning more about ANDEMBRY or accessing the therapy are encouraged to utilize ANDEMBRY ConnectSM, designed to offer comprehensive support and assistance through various programs. For more information, call 844-423-4273 or visit About HAE HAE is a rare and potentially life-threatening genetic condition that occurs in about 1 in 10,000 to 1 in 50,000 people. HAE is caused by deficient or dysfunctional C1INH, a protein in the blood that helps to control inflammation. Inadequate amounts of properly functioning C1INH can lead to the accumulation of fluid in body tissues, causing considerable swelling referred to as angioedema. HAE attacks can affect many parts of the body, including the face, abdomen, larynx, and extremities. Patients who have abdominal attacks of HAE can experience extreme pain, diarrhea, nausea, and vomiting caused by swelling of the intestinal wall. HAE attacks that involve the face or throat can result in airway closure, asphyxiation and, if left untreated, death. About ANDEMBRYANDEMBRY is a novel monoclonal antibody inhibiting factor XIIa (anti-FXIIa mAb) that has completed the Phase 3 pivotal study as a new type of once-monthly subcutaneous prophylactic treatment for attacks related to HAE, a form of bradykinin-mediated angioedema. ANDEMBRY is CSL's first homegrown recombinant monoclonal antibody to gain FDA approval. It was discovered and optimized by scientists at CSL's Bio21-based research site, with formulation and manufacturing for the clinical programs completed at the CSL Broadmeadows Biotech Manufacturing Facility. ANDEMBRY uniquely inhibits the plasma protein, FXIIa. FXII is the first protein activated in the HAE pathway, initiating the cascade of events leading to an HAE attack. By targeting activated FXII (FXIIa), ANDEMBRY inhibits this cascade at the top as compared to other HAE therapies that target downstream mediators. About the VANGUARD Trial The multicenter, randomized, double-blind, parallel-group VANGUARD trial evaluated the efficacy and safety of ANDEMBRY, an investigational first-in-class monoclonal antibody, as a prophylactic treatment for patients with hereditary angioedema. Patients aged 12 years and older with HAE type I or II underwent screening and a run-in study period to verify a baseline attack rate. Patients were randomized 3:2 to receive a loading dose of 400 mg followed by 200 mg of ANDEMBRY monthly (n=39) or volume matched placebo monthly (n=25) subcutaneously. After the six-month treatment period, patients were given the opportunity to continue into the open-label extension study, which is currently ongoing. The ongoing open-label extension of the Phase 3 VANGUARD study is evaluating the long-term safety and efficacy of ANDEMBRY (200 mg monthly) for the prophylactic treatment of hereditary angioedema attacks. IMPORTANT SAFETY INFORMATION What is ANDEMBRY?ANDEMBRY® (garadacimab-gxii) injection, for subcutaneous use, is a prescription medication used to prevent attacks of hereditary angioedema (HAE) in people 12 years and older. It is not known if ANDEMBRY is safe and effective in children under 12 years of age. What should I tell my healthcare provider before using ANDEMBRY?Before using ANDEMBRY, tell your healthcare provider about any medical condition you may have, especially if you are pregnant, planning to become pregnant, breastfeeding, or planning to breastfeed. It is not known if ANDEMBRY can harm your unborn baby or if ANDEMBRY passes into breastmilk. Talk to your healthcare provider about the best way to feed your baby while using ANDEMBRY. Tell your healthcare provider about all medications you take, including prescription medicines, over-the-counter treatments, vitamins, and herbal supplements. How should I use ANDEMBRY? Use ANDEMBRY exactly as instructed by your healthcare provider. Detailed instructions for use can be found in the patient information section of the full prescribing information. ANDEMBRY is given as an injection under your skin (subcutaneous) by you or a caregiver. Your healthcare provider should show you or your caregiver how to prepare and inject your dose of ANDEMBRY before you inject yourself for the first time. Do not try to inject ANDEMBRY unless you have been trained by your healthcare provider. What are the possible side effects of ANDEMBRY?The most common side effects of ANDEMBRY include: Redness, itchiness, and bruising (injection-site reactions) Stomach (abdominal) pain Runny or stuffy nose, sneezing, watery eyes (nasopharyngitis) Please see full prescribing information for ANDEMBRY, including patient information and instructions for use. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. You can also report side effects to CSL Behring's Pharmacovigilance Department at 1-866-915-6958. About CSLCSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses: CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 32,000 people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For more information about CSL, visit Media ContactsValerie BombergerCSLOffice: +1 610-291-5388 Mobile: +1 267-280-3829 Email: Etanjalie Ayala CSL Behring Mobile: +1 610 297 1069 Email: Greg HealyCSLMobile: +1 610-906-4564Email: In Australia: Kim O'DonohueCSLMobile: +61 449 884 603Email: Brett FoleyCSLMobile: +61 461 464 708 Email: Investors ContactChris CooperCSLMobile: +61 455 022 740Email:
Yahoo
20-02-2025
- Health
- Yahoo
CSL Receives Approval in Japan for ANDEMBRY® (garadacimab) Subcutaneous (S.C.) Injection 200mg Pens, a Novel Human Anti-Activated Factor XII Monoclonal Antibody for the Prevention of Acute Attacks of Hereditary Angioedema (HAE)
ANDEMBRY® is a first-in-class monoclonal antibody treatment that inhibits activated Factor XII (FXIIa), the initiating factor in the HAE pathway, and offers the first pre-filled pen presentation enabling once-monthly subcutaneous administration The approval is based on the results of the international pivotal Phase 3 VANGUARD trial, which included HAE patients from Japan CSL is dedicated to improving the lives of those with HAE – a community that we have proudly supported for more than 40 years TOKYO, Feb. 20, 2025 /PRNewswire/ -- CSL Behring K.K. (Headquarters: Minato-ku, Tokyo; President and Representative Director: Izumi Yoshida) today announced that it has received manufacturing and marketing approval from Japan's Ministry of Health, Labour and Welfare (MHLW) for ANDEMBRY® (garadacimab) Subcutaneous (S.C.) Injection 200mg Pens. The product is approved for the prevention of acute attacks of hereditary angioedema (HAE) and is the first pre-filled pen presentation for once-monthly subcutaneous administration for long-term prophylaxis of HAE. The approval in Japan follows additional recent approvals received in Australia, the United Kingdom, and the European Union. ANDEMBRY is the first fully human monoclonal antibody in Japan designed to inhibit activated Factor XII (Factor XIIa), which initiates the cascade of events leading to angioedema at various sites of the body. "ANDEMBRY represents a major advancement in the management of hereditary angioedema, offering people living with this life-threatening condition long-term disease control through a patient-centric and convenient administration method," said Bill Mezzanotte, MD, Executive Vice President, Head of R&D, CSL. "As CSL's first approved recombinant monoclonal antibody discovered and developed entirely by CSL, ANDEMBRY underscores our more than 40-year commitment to HAE research and treatment optimization. This milestone is the result of decades of dedication, and we extend our gratitude to the colleagues, physicians and patients who made this possible for HAE patients and CSL." HAE is a rare, chronic, debilitating, and potentially life-threatening genetic disorder characterized by recurrent and unpredictable attacks of angioedema. Attacks are often painful and can occur in multiple sites of the body, including the abdomen, larynx, face, and extremities. HAE is designated as one of Japan's intractable diseases under the category of "Primary Immunodeficiency Syndrome." Reports indicate that approximately 430 patients in Japan are currently diagnosed and receiving treatment. According to global data, the prevalence of HAE is estimated to be 1 in 50,000 people, suggesting there may be approximately 2,500 patients in Japan. The approval of ANDEMBRY is based on the efficacy and safety data from the pivotal international Phase 3 VANGUARD trial and its open-label extension study. The detailed results of the VANGUARD trial were published in The Lancet in April 2023 and the primary results of the ongoing open-label extension study were published in Allergy (October 2024). A plain language summary of the VANGUARD trial findings has also been published to facilitate understanding of patients and caregivers of the clinical trial data. This summary is accessible in multiple languages, including English and Japanese. "ANDEMBRY is a breakthrough therapy as the first and only treatment targeting activated Factor XII, the key initiator of HAE attacks," said Dr. Rose Fida, Executive Director and Regional Lead, CSL R&D Japan & China. "With its novel mechanism, once-monthly subcutaneous dosing and easy-to-use pre-filled pen, ANDEMBRY is set to transform the way HAE is managed in Japan." About ANDEMBRY® (garadacimab)ANDEMBRY (garadacimab) is a novel Factor XIIa-inhibitory monoclonal antibody (anti-FXIIa mAb) that has completed Phase 3 clinical development as a new type of once-monthly subcutaneous prophylactic treatment for attacks related to HAE, a form of bradykinin-mediated angioedema. ANDEMBRY is CSL's first homegrown recombinant monoclonal antibody to gain approval. It was discovered and optimized by scientists at CSL's Bio21-based research site, with formulation and manufacturing for the clinical programs completed at the CSL Broadmeadows Biotech Manufacturing Facility. ANDEMBRY uniquely inhibits the plasma protein, FXIIa. When FXII is activated, it initiates the cascade of events leading to edema formation. By targeting FXIIa, ANDEMBRY inhibits this cascade at the top as compared to other HAE therapies that target downstream mediators. As of February 2025, ANDEMBRY® has been approved by the Australian Therapeutic Goods Administration (TGA) on January 14, 2025, the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) on January 24, 2025, and by the European Union's European Commission (EC) on February 10, 2025. About "ANDEMBRY® S.C. Injection 200mg Pens" Trade name ANDEMBRY® S.C. Injection 200mg Pens Indications or effects Prevention of acute attacks of Hereditary Angioedema (HAE) Dosage and administration In general, administer subcutaneously the initial loading dose 400 mg of Garadacimab (Genetical Recombination), followed by 200 mg once a month for adults and pediatric patients aged 12 years and older. Date of approval February 20, 2025 Manufacturing and marketing CSL Behring K.K. About CSL Behring Behring is a global leader in developing and delivering high-quality medicines that treat people with rare and serious diseases. In Japan, our core focus areas include immunology and rare diseases, hemophilia, as well as critical care and more information, please visit About CSLCSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses: CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 32,000 people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. Media ContactValerie Bomberger, CSLOffice: +1 610-291-5388 Mobile: +1 267-280-3829 Email: In Australia: Brett Foley, CSLMobile: +61 461 464 708Email: Investor Relations:Chris Cooper, CSLMobile: +61 455 022 740Email: View original content to download multimedia: SOURCE CSL Sign in to access your portfolio
