Columvi became the first bispecific antibody with a fixed treatment duration to attain accelerated approval from the FDA and conditional marketing authorization from the European Commission. These authorizations were granted to treat individuals with R/R DLBCL after undergoing two or more rounds of systemic therapy. The basis for these approvals stemmed from the encouraging outcomes of Columvi when used as a standalone treatment, as demonstrated in the pivotal Phase I/II NP30179 trial involving patients with R/R DLBCL who had received two or more previous treatments.
Columvi is a type of bispecific antibody that activates CD20 and CD3 in T-cells. It’s made to be readily available for infusion, allowing patients to begin treatment shortly after diagnosis. This is especially crucial for individuals with very aggressive diseases that could progress rapidly. Columvi is administered for a set period, providing patients with R/R DLBCL an endpoint to their treatment and the chance for a period without treatment, which differs from ongoing therapies.
Latest Novartis Fabhalta Results Highlight a Substantial 38.3% Drop in Proteinuria Versus Placebo Among IgAN Patients, Indicating Significant Clinical Benefit
Novartis shared findings from a planned mid-study examination of the Phase III APPLAUSE-IgAN trial of Fabhalta® (iptacopan), a Factor B inhibitor under investigation for its effects on the alternative complement pathway in patients with IgA nephropathy (IgAN). The results revealed that individuals receiving Fabhalta experienced a substantial 38.3% (p<0.0001) decrease in proteinuria, as indicated by the 24-hour urine protein to creatinine ratio (UPCR), after 9 months compared to those on placebo alongside standard care.
A decrease in proteinuria is now more widely acknowledged as a reliable indicator linked to the advancement toward kidney failure. It has been employed as a key measure in clinical trials for IgAN to facilitate quicker approvals. The research also demonstrated that Fabhalta was well received with a positive safety record consistent with earlier findings. These findings were unveiled today in a significant session on late-breaking clinical trials at the World Congress of Nephrology (WCN) held in Buenos Aires, Argentina.
“In IgAN, the alternative complement pathway, a component of the immune system, can become excessively active within the kidneys. This triggers an inflammatory reaction, resulting in a gradual decline in kidney function and progressive kidney damage. The impact of this decline in kidney function, coupled with the potential adverse effects of previous IgAN treatments, has a substantial effect on patients’ lives,” explained Professor Dana Rizk, an Investigator and member of the APPLAUSE-IgAN Steering Committee, as well as a professor in the UAB Division of Nephrology. “Fabhalta represents the initial potential treatment for IgAN designed to specifically target the alternative complement pathway.”
This planned interim assessment involved 250 patients for assessing effectiveness and 443 for evaluating safety. The APPLAUSE-IgAN investigation remains ongoing in a double-blind manner, hence restricting the disclosure of detailed interim findings. The submission for potential accelerated approval by the FDA has been accepted and is undergoing priority review. The primary goal, which assesses Fabhalta’s capacity to decelerate IgAN advancement by analyzing the annualized total estimated glomerular filtration rate (eGFR) change over 24 months, is anticipated upon the study’s conclusion in 2025.
Vertex Announces Acquisition Deal with Alpine Immune Sciences
Vertex Pharmaceuticals Incorporated and Alpine Immune Sciences, Inc. have revealed a firm agreement where Vertex will purchase Alpine at $65 per share, totaling around $4.9 billion in cash. This deal has received unanimous approval from the boards of both companies and is expected to be finalized in the current quarter.
Reshma Kewalramani, M.D., FASN, Vertex’s Chief Executive Officer and President, expressed that Alpine aligns well with Vertex’s strategic goals. This move reinforces their commitment to leveraging scientific advancements to develop groundbreaking medicines aimed at addressing severe illnesses with significant unmet needs in specialized markets. Dr. Kewalramani eagerly anticipates integrating Alpine’s skilled team into Vertex, foreseeing an accelerated path for povetacicept, a potentially superior treatment for IgAN, to reach patients. Furthermore, Vertex is excited about exploring povetacicept’s potential as a comprehensive solution and intends to incorporate Alpine’s expertise in protein engineering and immunotherapy into Vertex’s capabilities.
Alpine’s lead molecule, povetacicept (ALPN-303), is a potent and effective inhibitor of both BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand). Progressing through Phase II trials, povetacicept has demonstrated promising efficacy as a potential top-tier treatment for IgA nephropathy (IgAN). IgAN, a severe and progressive autoimmune kidney disease leading to end-stage renal disease, currently lacks approved therapies addressing its root cause. Globally, IgAN stands as the most prevalent form of primary (idiopathic) glomerulonephritis, impacting an estimated 130,000 individuals in the U.S. Povetacicept is scheduled to advance into Phase III clinical trials by the latter half of 2024.
Because of how it works as both a dual BAFF/APRIL antagonist, povetacicept could be advantageous for individuals with additional severe autoimmune kidney conditions like membranous nephropathy and lupus nephritis, along with autoimmune cytopenias. Ongoing clinical research is focusing on renal conditions and autoimmune cytopenias.
FDA Grants Telix Pharmaceuticals’ TLX101-CDx Fast Track Designation
Telix has announced that the FDA has granted Fast Track designation for their investigational glioma imaging product, TLX101-CDx (Pixclara™, 18F-floretyrosine or 18F-FET). This designation specifically pertains to using positron emission tomography (PET) to characterize progressive or recurrent glioma. Simultaneously, Telix is in the final stages of preparing its US New Drug Application (NDA) for TLX101-CDx, focusing on this initial indication for both adult and pediatric patients. The Fast Track designation will facilitate an expedited review process and allow for closer consultation with the FDA. While amino acid PET is already included in US and European guidelines for glioma imaging, there is currently no FDA-approved targeted PET agent for brain cancer imaging in the US Telix aims to make this product available commercially in the US, significantly improving patient access to this vital imaging agent.
Thomas A. Hope, MD, who holds the position of Professor of Radiology at UCSF, emphasized the pressing requirement to enhance the diagnosis and treatment of glioma, especially after treatment. He expressed enthusiasm about utilizing the clinical expertise at UCSF to expand the availability of this investigational substance. According to him, 18F-FET could play a significant role in distinguishing whether a glioma is genuinely advancing or experiencing a treatment-related alteration, termed pseudo-progression, a scenario where the standard MRI often yields inconclusive results.
Telix has a special partnership for research and data access with the University of California, San Francisco (UCSF), a prominent academic institution known for its clinical studies on FET PET4’s applications in various brain-related cancers. This collaboration between academia and industry, focused on joint development and market launch, will pave the way for Telix to provide TLX101-CDx as a commercial offering in the U.S., pending regulatory clearance.
FDA Grants Orphan Drug Designation (ODD) to NM5072 for Paroxysmal Nocturnal Hemoglobinuria (PNH)
NovelMed revealed that the FDA has granted Orphan Drug Designation (ODD) to NM5072, an anti-Properdin antibody that blocks the Alternative Pathway (AP), for managing Paroxysmal Nocturnal Hemoglobinuria (PNH) in patients. NM5072’s development is focused on PNH patients both in the United States and worldwide. The FDA confers ODD status on new medicines aimed at treating, diagnosing, or preventing rare diseases or disorders affecting fewer than 200,000 individuals in the United States.
Dr. Rekha Bansal, the CEO, mentioned that PNH is a rare disease affecting various blood cells, leading to challenging symptoms like anemia, fatigue, and intense pain, which can shorten lives if not treated. The existing treatment methods need enhancement. There’s optimism that NM5072, with its distinct way of targeting the beginning of the complement cascade, could offer a hopeful solution to enhance patient outcomes. NM5072 is currently undergoing regulatory evaluation for various uses in the USA and worldwide.
PNH is a rare, chronic, inflammatory, and hemolytic disorder that arises when Red Blood Cells (RBCs) affected by PNH break down both within and outside blood vessels, resulting in anemia that can have fatal consequences. Beyond PNH RBCs, other cells like Neutrophils, Monocytes, and Platelets contribute to cellular breakdown and inflammation, causing enduring impacts on the patient’s well-being. Without treatment or incomplete treatment, the condition can persist, resulting in anemia and inflammation, potentially resulting in chronic pain, fatigue, and other typical PNH symptoms.
