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Business Wire
4 days ago
- Business
- Business Wire
Otsuka Sibeprenlimab Phase 3 Data Show a Statistically Significant and Clinically Meaningful Proteinuria Reduction for the Treatment of Immunoglobulin A Nephropathy (IgAN)
PRINCETON, N.J. & TOKYO--(BUSINESS WIRE)--Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical, Co. Ltd. (Otsuka) today presented results from a pre-specified interim analysis of the Phase 3 VISIONARY study (NCT05248646) evaluating sibeprenlimab, for the treatment of immunoglobulin A nephropathy (IgAN) in adults. Patients treated with sibeprenlimab achieved a 51.2% (P<0.0001) reduction in proteinuria (as measured by 24-hour uPCR [urine protein-to-creatinine ratio]) at nine months of treatment when compared to placebo 1. The data were presented during a late-breaking clinical trials session at the European Renal Association (ERA) Congress in Vienna, Austria. The study, the largest Phase 3 IgAN trial conducted to date, also showed the safety profile of sibeprenlimab was favorable and consistent with previously reported data 1. Specifically, 76.3% of patients treated with sibeprenlimab experienced any Treatment Emergent Adverse Event (TEAE) versus 84.5% in the placebo group. 1 Patients who experienced a serious TEAE were 3.9% treated with sibeprenlimab compared to 5.4% treated with placebo. Sibeprenlimab received Priority Review designation from the FDA last month following its BLA filing in March. Proteinuria reduction is a recognized surrogate marker correlating with delaying progression to kidney failure and has been used as an endpoint in IgAN clinical trials to support accelerated regulatory approvals 2. Sibeprenlimab is an investigational monoclonal antibody that selectively inhibits the activity of APRIL (A PRoliferation-Inducing Ligand) in adults with IgAN. APRIL plays a key role in the 4-hit process of IgAN pathogenesis and is an important initiating and sustaining factor in IgAN progression by promoting the production of pathogenic Gd-IgA1 and immune complex formation 3,4,5,6. By selectively binding and inhibiting APRIL, sibeprenlimab reduces the amount of immunoglobulin A (IgA) and Gd-IgA1 levels 1. Lower levels of Gd-IgA1 in people with IgAN provide less substrate for immune complex formation 7. Sibeprenlimab is administered in a single-dose prefilled syringe for subcutaneous injection every four weeks intended for self-administration or administration by caregiver, providing patients the option of convenience at home. 'We are confident about the potential of sibeprenlimab and are grateful to the patients who are helping to further the science by participating in these important trials,' said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. 'Proteinuria control is an important independent predictor for long-term prognosis, and this interim data reinforces our belief that selectively targeting APRIL has the potential to be an effective and safe approach for this progressive and irreversible kidney disease.' The VISIONARY study continues in a blinded manner to evaluate the change in kidney function over 24 months as measured by estimated glomerular filtration rate (eGFR) and is expected to be completed in early 2026. Further prespecified and exploratory analyses of the data will be conducted to determine the full potential of sibeprenlimab for the treatment of IgAN 1. 'The VISIONARY Phase 3 interim analysis shows a robust proteinuria reduction of 51.2% in the group treated with sibeprenlimab relative to placebo. These results affirm our belief in the efficacy of sibeprenlimab in the largest Phase 3 IgAN trial to date. The study enrolled a diverse patient population reflective of the disease epidemiology,' said Dr. Dana Rizk, professor of medicine in the division of nephrology at the University of Alabama at Birmingham. 'The safety data emerging from VISIONARY is reassuring and adds to our existing knowledge about sibeprenlimab's safety profile from prior programs. This is very exciting news for patients and adds a therapeutic option with a novel mechanism of action potentially targeting the immunologic pathogenesis of IgAN.' About the VISIONARY Study The VISIONARY study is the largest IgAN trial to date, and is a multicenter, randomized, double-blind, placebo-controlled trial consisting of approximately 510 adult patients with IgAN who were receiving standard-of-care therapy (defined as maximally tolerated ACE inhibitor or ARB +/- SGLT2 inhibitor), designed to evaluate the efficacy and safety of sibeprenlimab 400 mg administered subcutaneously every four weeks, compared to placebo 1. The primary efficacy endpoint is to evaluate the change in 24-hour uPCR at 9 months compared with baseline. The secondary endpoint is to evaluate the annualized slope of eGFR estimated over ~24 months 1. About Sibeprenlimab Sibeprenlimab (formerly VIS649) was designed and engineered by Visterra, Inc., a wholly owned subsidiary of Otsuka. Pre-clinical and early-stage trials of sibeprenlimab were also conducted by Visterra. Sibeprenlimab is an investigational monoclonal antibody that selectively binds to and inhibits the activity of APRIL and plays a key role in the 4-hit process. By selectively binding and inhibiting APRIL, sibeprenlimab reduces the amount of immunoglobulin A (IgA) and Gd-IgA1 levels 1. Lower levels of Gd-IgA1 in people with IgAN provide less substrate for immune complex formation 7. Decreased immune complex formation should result in diminished deposition in the kidney, and reduced proteinuria and kidney inflammation 8. By reducing the production of Gd-IgA1, sibeprenlimab may help slow kidney damage and progression toward ESKD 3,4,5,6. By inhibiting APRIL, sibeprenlimab may help address one of the IgAN-specific drivers for nephron loss. About IgAN and APRIL IgAN is a progressive, immune-mediated, chronic kidney disease that typically manifests in adults aged 20-40 years and leads to ESKD over the lifetime of most patients 9,10,11. IgAN is characterized by the accumulation of Gd-IgA1 complexes in the kidneys. IgAN can lead to progressive loss of kidney function and, eventually, ESKD, imposing a significant burden on patients 10. Despite supportive care, there is an unmet need for treatments that address the root causes of the condition. Continued research in the disease remains crucial to uncovering opportunities for advancement in our understanding and treatment of patients 5. APRIL, a cytokine in the tumor necrosis factor (TNF) family, is integral to the pathogenesis and progression of IgAN. It promotes the survival and class switching of B cells to produce IgA, particularly the pathogenic galactose-deficient IgA1 (Gd-IgA1) that forms immune complexes in the kidneys 5. About Otsuka Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a 'big venture' company at heart, applying a youthful spirit of creativity in everything it does. Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies' 2,250 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs. OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Co., Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 35,340 people worldwide and had consolidated sales of approximately USD 14.7 billion in 2024. All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at and connect with us on LinkedIn and Twitter at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.'s global website is accessible at About Visterra Visterra is a biologics research and early-stage clinical development biotechnology company committed to developing innovative antibody-based therapies for the treatment of patients with immune-mediated kidney diseases and other hard-to-treat diseases. Its proprietary Hierotope® platform enables the design and engineering of precision biologics-based product candidates that specifically bind to, and modulate, key disease targets that are not adequately addressed by traditional therapeutic approaches. The platform also includes Fc engineering capabilities for half-life extension, bispecific antibodies and antibody-drug conjugates (ADCs). Visterra's pipeline includes programs targeting kidney diseases, immunologically-driven diseases and infectious diseases. Visterra is an indirect subsidiary of Otsuka Pharmaceutical Co., Ltd. For more information, visit References Otsuka Pharmaceutical Development & Commercialization, Study: Phase 3 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy (IgAN). Thompson A, Carroll K, Inker LA, et al. Proteinuria Reduction as a Surrogate End Pointin Trials of IgA Nephropathy. Clin J Am Soc Nephrol. 2019;14(3): Mathur M, Barratt J, Suzuki Y, et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 (Sibeprenlimab), an APRIL-Neutralizing IgG2 Monoclonal Antibody, in Healthy Volunteers. Kidney Int Rep. 2022;7(5):993-1003. Chang S, Li XK. The Role of Immune Modulation in Pathogenesis of IgA Nephropathy ( Cheung CK, Barratt J, Liew A, Zhang H, Tesar V, Lafayette R. The role of BAFF and April in IGA nephropathy: Pathogenic mechanisms and targeted therapies. Frontiers in nephrology. February 1, 2024. Mathur M, Barratt J, Chacko B, et al. A Phase 2 Trial of Sibeprenlimab in Immunoglobulin A Nephropathy Patients. NEJM. 2023 Gharavi, Ali G, et al. 'Aberrant Iga1 Glycosylation Is Inherited in Familial and Sporadic IGA Nephropathy.' Journal of the American Society of Nephrology : JASN, U.S. National Library of Medicine, May 2008, Kant, Sam, et al. 'Advances in Understanding of Pathogenesis and Treatment of Immune-Mediated Kidney Disease: A Review - American Journal of Kidney Diseases.' American Journal of Kidney Diseases, Apr. 2022, Pitcher, D. Braddon, et. al Long-term outcomes in IGA nephropathy. Clinical journal of the American Society of Nephrology : CJASN. Lai K. Iga nephropathy. Nature reviews. Disease primers. 2016 Cheung, Chee Kay & Boyd, JKF & Feehally, J.. (2012). Evaluation and management of IgA nephropathy. Clinical Medicine. 12. s27-s30. 10.7861/clinmedicine.12-6-s27.
Yahoo
21-02-2025
- Science
- Yahoo
X-37B Spaceplane Shares Earth Image For First Time As New Mission Details Emerge
For the first time, the U.S. Space Force has released a photo of Earth taken by one of its secretive X-37B mini-shuttles. The image appears to be the first in-orbit shot from the craft of any kind to be officially released by the Pentagon. However, a brief video clip published in 2023 did show the service-module-equipped X-37B separating from its launch rocket after being lofted into space in 2020. The new photo, published by the Defense Visual Information Distribution Service (DVIDS) yesterday, shows Earth captured by an X-37B's onboard camera, during its seventh mission, sometime last year. The image was taken 'while conducting experiments in a highly elliptical orbit,' and the camera itself is primarily used to 'ensure the health and safety of the vehicle,' the Space Force says. The caption notes that the X-37B's seventh mission included, for the first time, a series of aerobraking maneuvers, used to change its orbit using minimal fuel. The seventh X-37B mission, known as OTV-7, launched from the Kennedy Space Center in Florida on December 28, 2023. The X-37B is still in orbit now, having passed 400 days in orbit on January 31 this year. You can find out more about the mission in TWZ's previous reporting. In general, the Boeing-built X-37B has been incredibly camera-shy. Before the photo published yesterday, and the video clip from 2023, the U.S. Space Force and Boeing only released the first pictures of the service module — including ones showing the U.S. Air Force Academy's FalconSat-8, a small cubesat, and other payloads loaded onto it — after the conclusion of the OTV-6 mission in 2022. The montage begins at approximately 3:38 in the runtime: Watch Falcon Heavy launch the USSF-52 mission to orbit — SpaceX (@SpaceX) December 29, 2023 Boeing also previously released footage of an X-37B without the service module separating from its launch rocket during the OTV-1 mission, which began on April 22, 2010, and ended on December 3 of that year. This level of secrecy is hardly surprising given that the X-37Bs and their missions remain highly classified. This, in turn, has led to much speculation about their functions, including their potential use as space-based intelligence, reconnaissance, and surveillance (ISR) or weapons platforms. TWZ has discussed what is known about these spaceplanes and their capabilities in depth in the past. As for OTV-7, some details about the mission have gradually emerged, adding to what we already knew about it when it began. The launch, also known as USSF-52, used a Falcon Heavy rocket for the first time, meaning that the X-37B could be placed in a much higher orbit than on previous missions, as TWZ previously explored. FALCON HEAVY TRANSITS THE MOON: Tonight's launch of the USSF-52 mission with seventh mission of the Space Force's X-37B spaceplane. — John Kraus (@johnkrausphotos) December 29, 2023 From the outset, Space Force had confirmed that OTV-7 would 'include operating the reusable spaceplane in new orbital regimes,' implying that the mission would take the X-37B beyond the so-called geostationary orbit (GEO) belt around the Earth, as you can read more about here. Orbits that take spacecraft beyond the GEO belt — which is defined as being around 22,236 miles (35,786 kilometers) above sea level — are categorized as high-Earth orbits (HEO). Furthermore, OTV-7 involves taking the X-37B for the first time on a highly elliptical orbit (confusingly, also known as HEO). In the past, former Air Force Secretary Heather Wilson referred to the X-37B's ability to operate on a highly elliptical orbit, an egg-shaped trajectory that allows it to maneuver itself once it's close enough to the atmosphere. The advantage of this is that it allows the spaceplane to reappear unexpectedly in orbit, making it harder for any potential adversaries to track.'We know that that drives them nuts, and I'm really glad about that,' Wilson said, back in 2019. A key aspect of the X-37B is that it is highly maneuverable and the spaceplanes have been observed changing their positions during previous missions. The Space Force had previously said that OTV-7 would include 'experimenting with future space domain awareness technologies, and investigating the radiation effects on materials provided by NASA.' As far as payloads for OTV-7 are concerned, the Space Force has so far only revealed that the X-37B is carrying NASA's Seeds-2 experiment, which will explore what happens to plant seeds exposed to 'the harsh radiation environment of long-duration spaceflight.' We now know a little more about some of the various aspects of the mission, including that Boeing developed a new collision avoidance system ahead of OTV-7. For the current mission, the Space Force has identified about '1.7 million collision avoidance opportunities,' Chief of Space Operations Gen. Chance Saltzman told Aviation Week in a recent interview, referring to the threat posed by the proliferation of manmade objects in space. The aforementioned aerobraking maneuver is another key aspect of OTV-7. According to Aviation Week, the X-37B vehicle needed some modifications, covering 'fault protection, autonomy, and collision avoidance' to make it capable of this maneuver. This involves the spaceplane using the drag of the atmosphere to dip into low-Earth orbit (LEO), during which it can separate from its service module. You can read more about the aerobraking maneuver in the context of the X-37B in this previous story. Saltzman told the same publication that the aerobraking maneuver was also used to evaluate the Space Force's Space Surveillance Network, a collection of optical and radar sensors used to detect, track, identify, and catalog all human-made objects in orbit. Finally, OTV-7 has been exploring autonomy, seen as vital as space becomes increasingly busy, especially since spaceplanes like the X-37B operate in various regimes. Saltzman also said in the interview that there were no plans to use the X-37B as an operational vehicle, but it's clearly being used to gather data that will inform both potential future U.S. spaceplanes and also gain a better understanding of how adversaries could use similar systems. Most notably, China has been busy testing a spaceplane, named Shenlong (meaning Divine Dragon), which is understood to be broadly comparable to the X-37B. Some other details about the X-37B were recently provided to Aviation Week by Boeing's Michelle Parker, company vice president for space mission systems. She confirmed that the company has been conducting continual upgrades on the X-37B, including introducing new types of batteries and solar cells. 'Even though it may look the same, a lot of the innards have been upgraded and then can continue to fly for a significant amount of time,' Parker told the magazine. While we may still be being drip-fed new information about the X-37B, the fact that more is being disclosed may well reflect calls from U.S. officials and members of Congress to reveal more regarding military activity in and related to space. With the X-37Bs now assigned to the Space Force's main unit tasked with 'orbital warfare,' their military role is now made explicit. Meanwhile, more efforts have also been made to try and communicate to the public about the importance of space to military operations (and daily life) and potential threats outside of the Earth's atmosphere, as well as what the U.S. government is doing about those issues. Bearing in mind the activities of near-peer adversaries like China or Russia, space is now indisputably a key military domain and potential battlefield in future conflicts. In particular, the ability of China and Russia to threaten U.S. and allied activities in space via various anti-satellite weapons is a growing area of concern. Currently, it's unclear to what degree the new Trump administration might change how sensitive U.S. military space missions might be communicated to the public. However, the release of a photo showing — for the first time — the Earth seen from an X-37B is certainly a welcome glimpse into the still-secretive world of these hard-working spaceplanes. Contact the author: thomas@
