To Evaluate the Tolerance, PD, and PK of Lanthanum Polystyrene-sulfonate Powder in a Phase Ib/ IIa Clinical Trial in Patients With ESRD-HD Hyperphosphatemia With Multi-Center, Multi-Dose, Give the Drug Multiple Time

Start Date18 May 2020

Sponsor / Collaborator

The First Hospital of Jilin University

ChiCTR-TRC-14004901

/ RecruitingPhase 4IIT

Treatment study of chronic kidney disease complications

Start Date05 Jul 2014

Sponsor / Collaborator-

100 Clinical Results associated with Tolevamer

100 Translational Medicine associated with Tolevamer

100 Patents (Medical) associated with Tolevamer

413

Literatures (Medical) associated with Tolevamer

15 Apr 2025·Nephrologie & Therapeutique

The effects of resins added to the milk of children suffering from chronic kidney disease: a clinical relevance to control potassium and phosphate levels?

Article

Author: Ranchin, Bruno ; Naud, Corentin ; Bechara, Rouba ; Chambon, Véronique ; de Mul, Aurélie ; Bacchetta, Justine

Background:

In infants with chronic kidney disease (CKD), the management of nutrition and growth is highly challenging, particularly compared to older children. Management of hyperkalemia and hyperphosphatemia is difficult, and incorporating potassium and phosphate binders directly in formulas could be beneficial, as it avoids direct ingestion of resins by infants.

Materials and methods:

We conducted a study using Gallia® standard first-stage infant formula and Pregestimil®. We added either carbonate sevelamer (Renvela®, 200, 400 or 800 mg) or polystyrene sulfonate (Resikali®, 2000, 4000 or 8000 mg) to 90 ml of formula. Additionally, we evaluated the combined use of the resins with Gallia® by adding in 90 mL 200 mg/2000 mg, 400 mg/4000 mg, and 200 mg/4000 mg of Renvela® and Resikali®, respectively. The Milk was decanted for 10 minutes, and the resulting supernatants were weighted and analyzed for osmolality and pH. Sodium, potassium, chlore, bicarbonate, magnesium, glucose, calcium, phosphate, protein, cholesterol, triglycerides, iron, folate, vitamin B12 levels were measured after centrifugation.

Results:

With polystyrene sulfonate, potassium levels in milk decreased in a dose-dependent manner, by 36%, 52% and 68%, respectively. Polystyrene sulfonate also reduced magnesium levels and increased both calcium concentration (from 9.7 to 21 mmol/L) and osmolality (from 359 to 423 mOsm/kg). No significant effect on phosphate was observed. Sevelamer decreased both calcium and phosphate concentrations in a dose-dependent manner, by 14%, 26% and 29%, and by 24%, 36% and 40%, respectively. Sevelamer also increased pH from 6.9 to 9.1, and decreased folate levels by 32%, 66% and 81% respectively, from 465 to 88 mmol/L. The combined use of sevelamer and polystyrene sulfonate results in decreased levels of potassium (by 45%, 59% and 59%, respectively), phosphate (by 38%, 39% and 36%, respectively), and folate, albeit with a slighter increase in pH. Osmolality remained unchanged and no other relevant differences were observed.

Conclusion:

Pretreating formulas with resins is a reproducible and straightforward method when specific diets for CKD are unavailable. However, it is important to keep in mind that resins may impact the overall composition (osmolality) and the concentration of other nutrients (folates).

01 Feb 2025·Lancet Regional Health-Europe

Comparative effectiveness of different therapies for Clostridioides difficile infection in adults: a systematic review and network meta-analysis of randomized controlled trials

Article

Author: Földvári-Nagy, László ; Erőss, Bálint ; Rancz, Anett ; Hegyi, Péter ; Simon, Viktor ; Bednárik, Dániel Steve ; Schnabel, Tamás ; Paraskevopoulos, Panagiotis ; Gede, Noémi ; Veres, Dániel Sándor ; Lenti, Katalin ; Földvári-Nagy, Kincső Csepke

Background:

Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea, with substantial morbidity and mortality. CDI is a severe and growing problem with numerous treatment options. We evaluated the effectiveness of all therapies in recurrent and non-recurrent infections and their prevention.

Methods:

This network meta-analysis and systematic review of randomized controlled trials (RCTs) compared all CDI therapies and preventions. We included RCTs published until 19 August 2024 and focused on adult population. We performed a systematic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Inclusion criteria were patients: adults (>16) treated against CDI; study type: randomized controlled trial; outcome: cure rate, recurrence or effectiveness of prevention. Any publication not meeting all criteria was considered to be ineligible and excluded. We applied random-effects meta-analysis using frequentist methods. We reported our main results as odds ratios (as a symmetric effect size measure, OR) with 95% confidence interval (95% CI). We used the Cochrane risk-of-bias tool to assess the risk of bias. Our study protocol was preregistered in PROSPERO (CRD42022371210).

Findings:

We assessed 73 RCTs with 28 interventions, involving 27,959 patients (49.2% female) in five networks. Fecal microbiota transplantation (FMT) was the most effective treatment in terms of the cure rate overall (P-score: 0.9952) and in recurrent cases (P-score: 0.9836). In recurrent cases, fidaxomicin (P-score: 0.6734) showed significantly greater effectiveness than vancomycin (P-score: 0.3677) and tolevamer (P-score: 0.0365). For non-recurrent CDI treatments ridinilazole, fidaxomicin, FMT and nitazoxanide were equally effective. Ridinilazole (P-score: 0.7671) and fidaxomicin (P-score: 0.7627) emerged as the most effective in preventing recurrence. Probiotics were not effective in preventing CDI, since network meta-analyses did not show significant differences between probiotics and placebo. In probiotics' subgroups pairwise meta-analyses Lactobacillaceae proved to be significantly more effective in prevention than placebo. Oral and colonoscopic FMT administration methods were equally effective. The study-level aggregated risk of bias of the publications included ranged from low to high. We observed relevant heterogeneity among studies in therapeutic doses, treatment durations, and follow-up times.

Interpretation:

The superiority of FMT in the treatment of CDI highlights the potential for increased use of FMT in clinical settings. Further research on optimizing FMT protocols and exploring its long-term safety and efficacy in larger samples is needed. Our findings suggest that the preventive use of probiotics might be questioned.

Funding:

None.

02 Jan 2025·ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Polyelectrolyte Additive‐Modulated Interfacial Microenvironment Boosting CO₂ Electrolysis in Acid

Article

Author: Dong, Lei ; Li, Chunzhong ; Ge, Wangxin ; Jiang, Hongliang ; Wang, Anqi ; Sheng, Xuedi ; Sun, Wen ; Zhang, Wenfei

Abstract:

Acidic CO2 electrolysis offers a promising strategy to achieve high carbon utilization and high energy efficiency. However, challenges still remain in suppressing the competitive hydrogen evolution reaction (HER) and improving product selectivity. Although high concentrations of potassium ions (K+) can suppress HER and accelerate CO2 reduction, they still inevitably suffer from salt precipitation problems. In this study, we demonstrate that the sulfonate‐based polyelectrolyte, polystyrene sulfonate (PSS), enables to reconstruct the electrode‐electrolyte interface to significantly enhance the acidic CO2 electrolysis. Mechanistic studies reveal that PSS induces high local K+ concentrations through the electrostatic interaction between PSS anions and K+. In situ spectroscopy reveals that PSS reshapes the interfacial hydrogen–bond (H‐bond) network, which is attributed to the H‐bonds between PSS anions and hydrated proton, as well as the steric hindrance of the additive molecules. This greatly weakens proton transfer kinetics and leads to the suppression of undesirable HER. As a result, a Faradaic efficiency of 93.9 % for CO can be achieved at 250 mA cm−2, simultaneous with a high single‐pass carbon efficiency of 72.2 % on commercial Ag catalysts in acid. This study highlights the important role of the electrode‐electrolyte interface induced by polyelectrolyte additives in promoting electrocatalytic reactions.

News (Medical) associated with Tolevamer

19 Sep 2024

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Global Pharmaceutical Industry Financing Transactions Weekly Report (9.9-9.15)

Pharmaceutical licensing collaboration1.Roivant Sciences Partners with Bayer On September 10, Roivant Sciences announced that it has obtained global rights to Bayer's soluble guanylate cyclase (sGC) activator, Mosliciguat. Bayer will receive an upfront payment of $14 million and up to $280 million in development, regulatory, and commercialization milestone payments. On the same day, Roivant Sciences announced the creation of a new subsidiary, Pulmovant, which will focus on the development of Mosliciguat. Mosliciguat is currently under development for the treatment of pulmonary arterial hypertension associated with interstitial lung disease (PH-ILD). Results from the Phase 1b proof-of-concept ATMOS study showed that at doses of 1 mg, 2 mg, and 4 mg, Mosliciguat reduced pulmonary vascular resistance by an average of 25.9%, 38.1%, and 36.3%, respectively, compared to baseline. 2.Gilead Sciences Partners with Genesis to Develop Novel Small Molecule Therapies On September 10, Gilead Sciences and Genesis Therapeutics announced a strategic collaboration to discover and develop novel small molecule therapies targeting multiple pathways. The partnership will leverage Genesis' artificial intelligence platform, GEMS, to assist in generating and optimizing molecules for Gilead's selected targets. The two companies will collaborate closely on preclinical research, with Gilead retaining exclusive rights to the potential clinical development and commercialization of any compounds developed through the partnership. Under the agreement, Genesis will receive a $35 million upfront payment and is eligible for additional preclinical, development, regulatory, and commercialization milestone payments. If Gilead successfully commercializes any collaborative products, Genesis will also be eligible for tiered royalties on net sales. 3.ITM Partners with Debiopharm On September 10, ITM announced a collaboration with Debiopharm, acquiring global exclusive development and commercialization rights for Debiopharm’s radiopharmaceutical program. This program combines the therapeutic compound Debio 0228 and the diagnostic imaging agent Debio 0328, both targeting carbonic anhydrase IX (CA IX). Under the agreement, Debiopharm will receive approximately €300 million in upfront, development, and regulatory milestone payments, as well as commercial milestones and low double-digit royalties on future sales. Debio 0228/0328 is a pair of investigational therapies. Debio 0328, a PET imaging agent that can be used independently, is designed to identify cancer patients who overexpress CA IX. Once identified, these patients can be treated with the lutetium-labeled radioligand Debio 0228, which aims to deliver targeted radiation to tumors for internal destruction. The program is currently being evaluated in a Phase 1/2 clinical trial for the treatment of clear cell renal cell carcinoma, pancreatic ductal adenocarcinoma, and colorectal cancer. 4.Novo Nordisk Reaches Another Agreement with Kallyope On September 10, Kallyope announced a licensing agreement with Novo Nordisk, under which Novo Nordisk exercised its option to use ligands identified by Kallyope for therapeutic development, including potential treatments for obesity. Novo Nordisk will be responsible for preclinical and clinical development, manufacturing, and commercialization, while Kallyope will receive upfront payments and may receive additional milestone payments and royalties based on sales. The two companies had previously collaborated to leverage Kallyope's Klarity platform to identify peptide-based therapies with the potential to improve obesity treatment outcomes. Preclinical data generated during this research suggested that ligands identified by Kallyope may have a beneficial effect on obesity patients. 5.Sanofi Enters Collaboration on Radioligand Therapy On September 12, Sanofi announced an exclusive licensing agreement with RadioMedix and Orano Med to jointly develop radio-ligand therapies (RLT) based on lead isotopes for cancer treatment. Under the agreement, RadioMedix and Orano Med will receive an upfront payment of €100 million and up to €220 million in sales milestone payments. The collaboration primarily focuses on the late-stage clinical program AlphaMedix, an alpha particle-based targeted therapy (TAT). Early clinical trials have demonstrated good tolerability and significant tumor burden reduction, with a 62.5% response rate among patients. The U.S. FDA recently granted breakthrough therapy designation to AlphaMedix for the treatment of gastrointestinal and pancreatic neuroendocrine tumors in patients who have not previously received peptide receptor radioligand therapy. The drug is currently nearing the completion of its Phase 2 clinical trial. 6.Harbour BioMed Partners with Umoja Biopharma On September 13, Harbour BioMed announced a multi-target antibody development collaboration with Umoja Biopharma. The partnership will leverage Harbour BioMed’s proprietary fully human heavy chain antibody (HCAb) platform to produce novel in vivo CAR-T cell therapies, further expanding the potential applications of this innovative delivery technology. The fully human HCAb features a compact size, simple structure, and precise binding capabilities, significantly reducing antibody immunogenicity while enhancing the flexibility and diversity of CAR design. 7.ENCell Partners with Lucy Biotech Recently, ENCell announced that it has signed a licensing and strategic alliance agreement with Lucy Biotech for the next-generation mesenchymal stem cell therapy, EN001. The agreement grants Lucy Biotech the rights to develop and commercialize EN001 in six Asian regions and countries, including Hong Kong, Taiwan, Macau, Vietnam, Thailand, and Singapore. According to the agreement, ENCell will receive an upfront payment of $1.5 million, as well as up to $18 million in milestone payments and royalties based on sales. EN001 is a clinical-stage mesenchymal stem cell therapy candidate produced from mesenchymal hematopoietic stem cells obtained in the early cultivation phase. Preclinical studies have shown that this product has potential in regenerating damaged nerves and muscles. The company has completed a Phase 1a clinical trial for patients with Charcot-Marie-Tooth disease type 1a and is currently conducting a Phase 1b trial for patients with Charcot-Marie-Tooth disease type 1A. Pharmaceutical Financing Events1.Superluminal Medicines Completes $120 Million Series A Funding Round On September 9, Superluminal Medicines announced the completion of a $120 million Series A funding round. The round was led by RA Capital Management, with participation from Insight Partners, NVentures, Eli Lilly, Gaingels, and others. The funds raised will support the company's lead projects entering the clinical development stage and increase the number of projects focusing on high-value G protein-coupled receptor (GPCR) small molecule drug discovery. Established in 2023, Superluminal focuses on membrane receptors that mediate cell signaling and the fundamental physiological responses in humans, constituting major categories of drug targets including GPCRs, ion channels, and transport proteins. The company's technology platform rapidly develops candidate compounds through an integrated approach combining expertise in biology and chemistry, machine learning, and proprietary big data infrastructure. Currently, the company is advancing six small molecule projects. 2.Bambusa Therapeutics Announces Completion of Approximately $15 Million Seed Funding Round On September 9, Bambusa Therapeutics has announced the completion of a seed funding round amounting to approximately $15 million. The round was co-led by BVF Partners and Dawn Biopharma, with participation from Salvia GmbH and INCE Capital. The funds raised will be used to accelerate the development of Bambusa’s bispecific antibody pipeline for Phase 1 clinical studies. Founded by a group of industry experts and scientific innovators, Bambusa aims to transform the treatment landscape for immunological and inflammatory diseases. The company leverages validated targets and employs innovative antibody engineering to create bispecific antibody therapies. 3.Candid Therapeutics Raises Over $370 Million On September 9, Candid Therapeutics announced it had raised more than $370 million in funding. The company is developing T-cell engager (TCE) antibodies that target specific B-cell populations for the treatment of autoimmune diseases. Through a three-way merger and multi-step financing, Candid acquired Vignette Bio and TRC 2004, gaining access to two TCE products—CND106 and CND261. CND106 is a BCMA/CD3 bispecific antibody, with Vignette Bio obtaining exclusive rights for its development and commercialization outside of Greater China through a collaboration with EpimAb Biotherapeutics. CND261 is a CD20/CD3 bispecific antibody, and TRC 2004 secured global exclusive licensing rights outside Greater China through a partnership with Genor Biopharma. Both products have completed Phase 1 dose-escalation studies. 4.JHM Biopharm Completes Over 200 Million RMB Series B+ Funding On September 10, JHM Biopharm announced that it had completed a Series B+ funding round exceeding 200 million RMB, led by SDIC Unity Capital. This follows the 100 million RMB Series B funding raised in late May from Tonghua Dongbao. The funds from this round will primarily be used to further advance the company’s pipeline and accelerate industrialization and commercialization efforts. Founded in November 2020, JHM Biopharm focuses on the development of innovative recombinant protein drugs and synthetic biology products in the fields of serious medical conditions, consumer healthcare, and metabolism. The company's main pipeline products include recombinant human type I collagen, recombinant human type III collagen, recombinant type A botulinum toxin, recombinant human growth hormone injections, and long-acting recombinant growth hormone. Notably, the Phase 2 clinical trial for recombinant type A botulinum toxin in treating moderate-to-severe glabellar lines in adults is nearing completion, with plans to enter Phase 3 trials soon. 5.Epsilogen Completes £12.5 Million Series B Expansion Financing On September 10, Epsilogen announced the completion of a £12.5 million Series B expansion financing round, bringing the total Series B funds raised to £43.25 million. The round saw participation from investors including British Patient Capital, Novartis Venture Fund, Epidarex Capital, 3B Future Health Fund, and ALSA Ventures. The funds from this round will be primarily used to progress the Phase 1b trial of the immunoglobulin E (IgE) antibody MOv18 IgE for the treatment of platinum-resistant recurrent ovarian cancer (PROC) to achieve proof of concept, as well as to further develop the company's IgE-based pipeline. MOv18 IgE is the first therapeutic IgE antibody to enter clinical trials, targeting the folate receptor alpha (FRα). In Phase 1 trials, the product has demonstrated good safety and tolerability, along with anti-tumor activity. 6.Base Therapeutics completes tens of millions of yuan in Series A2 financing On September 12, Base Therapeutics announced the completion of a multi-million yuan Series A2 financing round led by the AEF Greater Bay Area Venture Fund (AEF GBA Venture Fund). The funds raised will be used to strengthen the R&D team, optimize the product pipeline, and accelerate clinical trials. Established in 2021, Base Therapeutics focuses on foundational innovations in the field of gene editing. The company has developed the AccuBase base editing system, which enables efficient gene editing both in vitro and in vivo with zero off-target effects. Additionally, Base Therapeutics has also developed a range of leading-edge technologies including ePE, CasH gene editing technology, BEAT-CART technology, and in vivo targeted delivery technologies. Leveraging these technologies, Base Therapeutics is developing the BASE-NK and in vivo base editing product pipelines. Among these, the most advanced, NK510 cell injection, has already been submitted for an IND in China. This product, based on base editing technology, is a natural killer (NK) cell product intended for the treatment of advanced solid tumors. 7.Vironexis Biotherapeutics Announces Completion of $26 Million Seed Funding Round On September 13, Vironexis Biotherapeutics has announced the completion of a $26 million seed funding round. The round was led by Drive Capital and Future Ventures, with participation from Moonshots Capital and Capital Factory. Vironexis has developed the TransJoin adeno-associated virus (AAV) gene therapy platform and boasts over ten candidate products aimed at treating hematologic cancers, preventing solid tumor metastasis, and developing cancer vaccines. Among these, the lead gene therapy candidate, VNX-101, has been granted Fast Track and Rare Pediatric Disease designations by the FDA. Its Investigational New Drug (IND) application for the treatment of CD19-positive Acute Lymphoblastic Leukemia has also been approved by the FDA. The second project, VNX-202, targets the prevention of metastasis in HER2-positive cancers, including breast cancer and other tumor types, with Phase 1/2 clinical trials expected to commence in 2025. 8.Jingegg Biomedical has completed an A-round financing in the tens of millions of yuan Recently, Jingegg Biomedical has announced the completion of a multi-million yuan Series A financing round. The round was led by Triwise Capital, with continued additional investment from existing shareholders, Longmen Capital Management and Technology Financial Group. The funds raised will primarily be used to advance the development of its core pipeline and accelerate collaborations with multinational pharmaceutical companies. Founded in 2019, Jingegg Biomedical focuses on the research and development of innovative ion channel drugs for neuropsychiatric disorders and chronic kidney diseases. The company has established a technology platform for small molecule and protein drugs targeting ion channels, complemented by four major tool platforms, addressing the industry bottlenecks of low drug discovery success rate and significant side effects. Click on the image below to explore new pharmaceutical funding transactions!

19 Sep 2024

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Global New Drug Research and Development Progress Weekly Report (9.9-9.15)

What other drugs have been approved this week?1. Johnson & Johnson: New Indication for Guselkumab Approved by FDA On September 11, Johnson & Johnson announced that Guselkumab (brand name: Tremfya) received FDA approval for a new indication to treat moderate-to-severe active ulcerative colitis (UC) in adult patients. Guselkumab is an IL-23 inhibitor. Guselkumab was first approved by the FDA in July 2017 for the treatment of moderate-to-severe plaque psoriasis in adults, making it the world's first anti-IL-23 monoclonal antibody approved for psoriasis treatment. Since then, it has expanded to other indications, with approvals in regions like the U.S. and Japan for conditions including palmoplantar pustulosis and psoriatic arthritis. Post-launch, its sales have steadily increased, reaching global sales of $3.146 billion in 2023. This latest approval was based on results from the key Phase IIb/III QUASAR clinical trial, which showed that 50% of patients receiving 200 mg every 4 weeks and 45% of patients receiving 100 mg every 8 weeks achieved clinical remission at week 44, compared to 19% in the placebo group. 2. Eli Lilly: IL-13 Monoclonal Antibody Approved by FDA On September 13, Eli Lilly announced that its IL-13 monoclonal antibody, Lebrikizumab (brand name: Ebglyss), was approved by the FDA for the treatment of moderate-to-severe atopic dermatitis in adults and children aged 12 and above. This approval is primarily based on the results from the ADvocate 1, ADvocate 2, and ADhere studies, which evaluated the skin clearance of enrolled patients at week 16. The results showed that after 16 weeks of treatment, 38% of patients in the Ebglyss group achieved clear or almost clear skin (IGA 0 or 1), compared to 12% in the placebo group. Among those who achieved clear or almost clear skin, 77% maintained remission for up to one year with monthly dosing. On November 16, 2023, Lebrikizumab was also formally approved for marketing in the European Union. 3. Sanofi/Regeneron: New Dupilumab Indication Approved by FDA for Adolescents On September 13, Regeneron announced that Dupilumab (brand name: Dupixent) received FDA approval for a new indication as an add-on maintenance therapy for adolescents aged 12 to 17 with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP). This approval is primarily based on extrapolated efficacy data from two pivotal trials in adults with CRSwNP (SINUS-24 and SINUS-52), as well as safety data from other approved indications in adolescents. Dupilumab, the world’s first IL-4R monoclonal antibody, was initially approved in March 2017, with first-year sales of $251 million. Since then, Dupixent has expanded to additional indications, including asthma and nasal polyps. Now a blockbuster drug, Dupixent achieved global sales of $11.589 billion in 2023, marking a year-over-year growth of approximately 33%. In the first half of 2024, with sales of $6.66 billion, it surpassed AbbVie’s adalimumab ($5.084 billion) and Johnson & Johnson’s ustekinumab ($5.336 billion), making it the new leader in the autoimmune therapeutic space. 4.Sanhome Pharmaceutical: Third-Generation EGFR-TKI Approved for First-Line NSCLC Indication On September 9, the NMPA website announced that Sanhome Pharmaceutical’s Class 1 innovative drug, Oritinib Mesylate, has been approved for its second indication, as a first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations. In June of this year, the drug was also approved for second- and later-line treatment of adult patients with locally advanced or metastatic NSCLC harboring the EGFR T790M mutation who experienced disease progression during or after EGFR-TKI treatment. Additionally, a study (SHC013-III-02) investigating the use of Oritinib Mesylate as adjuvant therapy for post-operative stage II-IIIB NSCLC patients with EGFR mutations is currently ongoing. In a randomized, double-blind, multi-center phase III clinical trial comparing Oritinib Mesylate to Gefitinib in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR-sensitive mutations, the results showed that the median progression-free survival (PFS) assessed by the independent review committee (IRC) was 19.3 months for the Oritinib Mesylate group and 9.8 months for the Gefitinib group, marking an improvement of 9.5 months in median PFS with Oritinib Mesylate treatment compared to the standard treatment with Gefitinib. In terms of safety, most adverse events observed during the clinical trial were mild to moderate, with a low incidence of common side effects such as rash and hematologic toxicity. 5.Fosun Pharmaceutical: Daxxify, Approved for Facial Wrinkles in China On September 9, the NMPA website showed that Fosun Pharmaceutical’s Type A botulinum toxin product, Daxxify, has been approved for the temporary improvement of moderate to severe glabellar lines caused by the activity of the corrugator and/or procerus muscles in adults. Daxxify is developed based on Revance Therapeutics' proprietary TransMTs technology platform and is a next-generation neuromodulator containing a stabilizing peptide formulation and highly purified Type A botulinum toxin. It is the first and only long-acting peptide-based neuromodulator. In December 2018, Fosun Pharmaceutical entered into a collaboration and licensing agreement with Revance for the commercialization rights of Daxxify in mainland China, Hong Kong, and Macau, with a deal valued at $88 million. On September 8, 2022, Revance Therapeutics announced that the U.S. FDA had approved Daxxify for the temporary improvement of moderate to severe glabellar lines in adults. Daxxify does not contain human serum albumin or animal-derived ingredients, and its wrinkle-reducing effects last for a median duration of six months, with the maximum duration reaching up to nine months. In terms of safety, no severe treatment-related adverse events were reported, and its safety profile is consistent with other neuromodulators currently available in the aesthetic medicine market. 6.Otsuka Holdings: Third-Generation Bcr-Abl Inhibitor Ponatinib Approved in China On September 9, the NMPA website announced that Otsuka Holdings' submission for Ponatinib has been approved for the treatment of chronic myeloid leukemia (CML) and relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in patients who are resistant or intolerant to prior therapy, as well as for patients with T315I-positive CML or Ph+ ALL. Ponatinib was initially developed by Ariad Pharmaceuticals as a third-generation Bcr-Abl tyrosine kinase inhibitor. In December 2014, Otsuka Holdings entered into a partnership with Ariad to co-develop and commercialize Ponatinib in Japan, China, South Korea, and other Asian countries. In early 2017, Takeda Pharmaceuticals acquired Ariad and gained ownership of the product. 7.UCB: New Indication for IL-17A/F Monoclonal Antibody Approved in China On September 14, the NMPA website announced that UCB’s bimekizumab (Bimzelx) has been approved for a new indication in China, presumed to be for the treatment of non-radiographic axial spondyloarthritis (nr-axSpA). Bimekizumab is a humanized IgG1 monoclonal antibody developed by UCB that simultaneously inhibits both IL-17A and IL-17F, two key cytokines driving inflammatory processes. Prior to 2023, bimekizumab was approved in the European Union and Japan for four indications: plaque psoriasis, erythrodermic psoriasis, generalized pustular psoriasis, and pustular psoriasis, generating $160 million in sales in 2023. However, since the beginning of 2023, the drug has been approved in both the U.S. and China, with additional indications including ankylosing spondylitis, hidradenitis suppurativa, non-radiographic axial spondyloarthritis, and psoriatic arthritis. As a result, UCB predicts that the drug’s global peak sales could exceed $4 billion. 8.Merck: Keytruda Approved for a New Indication in China for First-Line Melanoma Treatment On September 14, Merck announced that its PD-1 inhibitor pembrolizumab (trade name: Keytruda) has been approved by the NMPA for first-line treatment of unresectable or metastatic melanoma. This approval updates the product label from "pembrolizumab is indicated for the treatment of unresectable or metastatic melanoma after failure of first-line therapy" to "pembrolizumab is indicated for the treatment of unresectable or metastatic melanoma." To date, pembrolizumab has been approved for over ten indications in China, covering a wide range of cancers, including melanoma, non-small cell lung cancer, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, colorectal cancer, hepatocellular carcinoma, triple-negative breast cancer, MSI-H/dMMR solid tumors, gastric cancer, and biliary tract cancer. What major clinical trial results were released this week?1.Akeso: AK112 Outperforms Keytruda in Head-to-Head Trial On September 8, Akeso announced at the 2024 WCLC the groundbreaking data from its pivotal Phase III study (HARMONi-2/AK112-303), comparing the PD-1/VEGF bispecific antibody Ivonescimab to pembrolizumab as a first-line treatment for locally advanced or metastatic PD-L1-positive (PD-L1 TPS ≥1%) non-small cell lung cancer (NSCLC). In the ITT population, Ivonescimab demonstrated a median progression-free survival (mPFS) of 11.14 months versus 5.82 months with pembrolizumab, with a PFS hazard ratio of 0.51 (P<0.0001), reducing the risk of disease progression or death by 49%. Ivonescimab also significantly improved the objective response rate (ORR) (50.0% vs. 38.5%) and disease control rate (DCR) (89.9% vs. 70.5%) in PD-L1-positive NSCLC patients, showcasing its superior antitumor efficacy. As of the data cutoff, overall survival (OS) results were still immature. 2.GSK: Positive TIGIT Antibody First-Line Treatment Results, Phase III Trial Launched iTeos Therapeutics presented promising results from its Phase II trial at ESMO for first-line treatment of PD-L1 high-expressing NSCLC. The study investigated the combination of GSK’s TIGIT antibody belrestotug and PD-1 inhibitor dostarlimab. A Phase III trial has already been initiated based on these findings. By June 7, 2024, the trial enrolled 124 patients receiving dostarlimab or belrestotug + dostarlimab at three dose levels. ORR in the belrestotug 100mg/400mg/1000mg groups showed significant clinical improvement, at 63.3%, 65.6%, and 76.7% respectively, compared to 37.5% in the dostarlimab monotherapy group. GSK entered a partnership with iTeos Therapeutics in 2021, with the deal potentially worth up to $2 billion, to co-develop the TIGIT antibody. 3.Hengrui Pharmaceutical: Clinical Results for Nectin-4, CLDN18.2, and TROP2 ADCs Released CLDN18.2 ADC: SHR-A1904 Hengrui Pharmaceuticals presented the results of its Phase I study of the CLDN18.2 ADC SHR-A1904 for the treatment of gastric or gastroesophageal junction cancer (GC/GEJC) in an oral report. This open-label, single-arm, multicenter Phase I clinical trial (NCT04877717) evaluated SHR-A1904 in patients with advanced solid tumors who had failed or had not received standard treatment. As of March 18, 2024, a total of 73 GC/GEJC patients were enrolled. Among them, 98.6% had metastatic disease, and 31.5% had received ≥3 prior treatments (median 2 treatments). The data showed that among patients who were assessed both at baseline and after ≥1 follow-up, in the 6.0 mg/kg dose group, the objective response rate (ORR) was 55.6% (5/9; 95% CI, 21.2-86.3), and the disease control rate (DCR) was 88.9% (8/9; 95% CI, 51.8-99.7). In the 8.0 mg/kg dose group, ORR was 36.7% (11/30; 95% CI, 19.9-56.1) and DCR was 86.7% (26/30; 95% CI, 69.3-96.2). Nectin-4 ADC: SHR-A2102 Hengrui also presented the Phase I results of SHR-A2102 for the treatment of advanced solid tumors in a poster presentation. As of April 9, 2024, 38 patients were enrolled (median age: 61 years; ≥3 prior lines of treatment: 60.5%; prior ICI treatment: 78.9%). Among the 30 patients evaluable for tumor response, the overall ORR was 23.3%, and the DCR was 76.7%. In 16 evaluable heavily pretreated NSCLC patients, the ORR was 31.3% (50.0% in non-squamous and 12.5% in squamous histology), and the DCR was 87.5% (75.0% in non-squamous and 100.0% in squamous). TROP2 ADC: SHR-A1921 In an oral presentation, Hengrui announced the first-in-human Phase I study results of TROP2 ADC SHR-A1921 for the treatment of platinum-resistant ovarian cancer. As of March 20, 2024, 46 patients with platinum-resistant ovarian cancer were enrolled (3.0 mg/kg, n=26; 2.0+2.0 mg/kg, n=20). Of these, 39.1% were primary platinum-resistant (defined as PFI <6 months after first-line platinum-based therapy), and 34.8% had a PFI <4 weeks after the most recent platinum-based therapy. A total of 78.3% had received ≥2 platinum-based therapies, and 45.7% received ≥1 non-platinum therapy after confirming platinum resistance. The majority of patients had received prior bevacizumab (69.6%) and PARP inhibitors (58.7%). The median follow-up was 7.4 months. Among evaluable patients, the ORR was 48.8% (21/43; 95% CI, 33.3-64.5), and the DCR was 97.7% (42/43; 95% CI, 87.7-99.9). The median duration of response (mDoR) was 6.4 months (95% CI, 4.7-not reached). Of the 21 confirmed responders, 47.6% (10/21) were still responding. The median progression-free survival (mPFS) was 7.2 months (95% CI, 4.4-11.1). Median overall survival (OS) was not reached, with a 6-month OS rate of 91.9% (95% CI, 76.9-97.3). SHR-A1921 showed efficacy at both 3.0 mg/kg and 2.0+2.0 mg/kg doses. Of the 46 patients, 23 (50.0%) experienced ≥Grade 3 treatment-related adverse events (TRAEs), with the most common (≥5%) being stomatitis (28.3%). No interstitial lung disease or TRAE-related deaths were reported. For more information on the progress of drug development, please consult the Synapse database.

10 Oct 2023

·synapse.patsnap.com

The "Antidote" Specific to Biological Toxins: Antitoxin

Antitoxin is a specific antibody or serum containing this antibody that can neutralize toxins. By using toxoids for immunization, the body can produce corresponding antitoxins to prevent diseases. Antibodies are glycoproteins produced by plasma cells after B cells are stimulated by antigens, which mainly exist in serum and other body fluids. They are important effector molecules mediating humoral immunity and can bind specifically with corresponding antigens to perform immune functions. Essentially, antitoxins are the corresponding antibodies or immune serums containing these antibodies to bacterial toxins (usually referring to exotoxins). They can neutralize the toxic effects of corresponding exotoxins. The body can produce antitoxins against pathogens that cause disease by producing exotoxins, such as diphtheria, tetanus, and gas gangrene bacteria. After treatment with formaldehyde, exotoxins can lose their toxicity while maintaining their immunogenicity, becoming toxoids. Antitoxin Competitive LandscapeAccording to Patsnap Synapse, as of 24 Sep 2023, there are a total of 36 Antitoxin drugs worldwide, from 25 organizations, covering 4 targets, 33 indications, and conducting 53 clinical trials. 👇Please click on the picture link below for free registration or login directly if you have freemium accounts, you can browse the latest research progress on drugs , indications, targets, organizations, clinical trials, and clinical results related to this drug type. Approved Antitoxon Medicinal: Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) The drug Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) - (Equine) is an antitoxin that targets BTX, which stands for botulinum toxin. It is primarily used for the treatment of botulism, a rare but serious illness caused by the toxin produced by the bacterium Clostridium botulinum. Botulism can lead to muscle weakness, paralysis, and potentially life-threatening complications. The drug falls under the therapeutic areas of infectious diseases and nervous system diseases, as it specifically addresses the effects of botulinum toxin on the body. By neutralizing the toxin, the antitoxin helps to alleviate the symptoms and prevent further damage caused by botulism. The drug received its first approval in the United States in March 2013. The originator organization of this drug is Emergent BioSolutions Canada, Inc. They are responsible for the development and production of the drug. The highest phase of development for this drug is approved, indicating that it has successfully completed clinical trials and has been granted regulatory approval for use. In summary, Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) - (Equine) is an antitoxin drug developed by Emergent BioSolutions Canada, Inc. It is used for the treatment of botulism, a serious illness caused by botulinum toxin. The drug has been approved and was first authorized for use in the United States in March 2013. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. Approved Antitoxon Medicinal: Centruroides (scorpion) immune F(ab)2Centruroides (scorpion) immune F(ab)2 is an antitoxin drug developed by Rare Disease Therapeutics, Inc. It falls under the therapeutic area of Other Diseases and is specifically designed to target scorpion venoms. The drug is primarily indicated for the treatment of drug intoxication, poisoning due to scorpion venom, and scorpion stings. Centruroides (scorpion) immune F(ab)2 received its first approval in the United States in August 2011. It is classified as an orphan drug, indicating that it is intended to treat rare diseases or conditions. As an antitoxin, Centruroides (scorpion) immune F(ab)2 works by neutralizing the toxic effects of scorpion venoms. Scorpion stings can cause severe symptoms, including pain, swelling, and potentially life-threatening complications. This antitoxin aims to alleviate these symptoms and improve patient outcomes. The drug has successfully completed its highest phase of development and has been approved for use. The approval of Centruroides (scorpion) immune F(ab)2 highlights its potential as a valuable treatment option for individuals affected by scorpion venom-related conditions. Since its approval, Centruroides (scorpion) immune F(ab)2 has been available in the United States to address the specific medical needs of patients suffering from scorpion venom intoxication, poisoning, and stings. The drug's approval as an orphan drug reflects the recognition of the limited treatment options available for these rare conditions and the importance of providing targeted therapies. 👇Please click on the image below to directly access the latest data (R&D Status | Core Patent | Clinical Trial | Approval status in Global countries) of this drug. In summary, Centruroides (scorpion) immune F(ab)2 is an antitoxin drug developed by Rare Disease Therapeutics, Inc. It is indicated for the treatment of drug intoxication, poisoning due to scorpion venom, and scorpion stings. The drug received its first approval in the United States in 2011 and is classified as an orphan drug. Its approval signifies its successful completion of the highest phase of development and highlights its potential as a valuable treatment option for individuals affected by scorpion venom-related conditions.

100 Deals associated with Tolevamer

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KEGG	Wiki	ATC	Drug Bank
-	Tolevamer	-	DB01344

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Diarrhea	Phase 3	Australia	Genzyme Corp.	01 Apr 2005
Diarrhea	Phase 3	Austria	Genzyme Corp.	01 Apr 2005
Diarrhea	Phase 3	Belgium	Genzyme Corp.	01 Apr 2005
Diarrhea	Phase 3	Czechia	Genzyme Corp.	01 Apr 2005
Diarrhea	Phase 3	Denmark	Genzyme Corp.	01 Apr 2005
Diarrhea	Phase 3	France	Genzyme Corp.	01 Apr 2005
Diarrhea	Phase 3	Germany	Genzyme Corp.	01 Apr 2005
Diarrhea	Phase 3	Ireland	Genzyme Corp.	01 Apr 2005
Diarrhea	Phase 3	Norway	Genzyme Corp.	01 Apr 2005
Diarrhea	Phase 3	Portugal	Genzyme Corp.	01 Apr 2005

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASN2019	Not Applicable	Hyperkalemia	-	Polystyrene Sulfonate (PS)	yhxwagfquc(uuuxwklvof) = avpxstliao itsueivcve (wacwdvctwr )	Negative	05 Nov 2019
NCT00196794 \| NCT00106509 (Pubmed \| Clin Infect Dis)	Phase 3	Clostridium difficile infection	-	Tolevamer 9g (loading dose) followed by 3g every 8 hours for 14 days	fvxwrvsheg(hogxcxtcrd) = tyvlayzhpv gqdokzeuwz (qtesanohnu )	-	01 Aug 2014
NCT00196794 \| NCT00106509 (Pubmed \| Clin Infect Dis)	Phase 3	Clostridium difficile infection	-	Vancomycin 125mg every 6 hours for 10 days	fvxwrvsheg(hogxcxtcrd) = yhpgqtxqar gqdokzeuwz (qtesanohnu )	-	01 Aug 2014
IAS2004	Not Applicable	-	-	PSS tablet	bnaykorzjc(vjttovppat) = no cytotoxicity vbiamtmkys (niqgmxmfyz ) View more	-	01 Jan 2004

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