Kiklin (bixalomer) / Astellas - LARVOL DELTA

Tenapanor administration combined with phosphate binders provides synergistic phosphate lowering effect (ERA 2025) - "Six types of P binders had been used in Group Ad (sevelamer hydrochloride, bixalomer, calcium carbonate, ferric citrate, sucroferric oxyhydroxide hydrate and lanthanum carbonate hydrate). Oral administration of tenapanor significantly reduced P adsorption and improved serum P level in patients undergoing HD either when it was administrated alone or adding on P binders. This P absorption reduction effect of tenapanor was greatly enhanced when it was added on P binders. The mechanism of this synergistic effect would be an important research question."

Metabolic Disorders • Nephrology • Renal Disease

Efficacy and Safety of Phosphate-Lowering Agents for Adult Patients with Chronic Kidney Disease Requiring Dialysis: A Network Meta-Analysis. (PubMed, Clin J Am Soc Nephrol) - "Compared with calcium-based agents, sevelamer was associated with lower all-cause mortality, and sucroferric oxyhydroxide and lanthanum were associated with slower progression of CACS. Potential benefits and harms should be considered when selecting phosphate-lowering agents (PROSPERO: CRD42022328388)."

Journal • Retrospective data • Cardiovascular • Chronic Kidney Disease • Gastrointestinal Disorder • Musculoskeletal Diseases • Nephrology • Renal Disease

Comparative Efficacy and Acceptability of 12 Phosphorus-Lowering Drugs in Adults with Hyperphosphatemia and Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis. (PubMed, Blood Purif) - "Magnesium carbonate has the best phosphorus-lowering effect in hyperphosphatemia adults with CKD; considering efficacy and acceptability, ferric citrate shows evidence to be the most appropriate drug with or without dialysis."

Clinical • Retrospective data • Review • Cardiovascular • Chronic Kidney Disease • Metabolic Disorders • Nephrology • Renal Disease

PHOSPHATE BINDERS FOR PATIENTS WITH CHRONIC KIDNEY DISEASE UNDERGOING DIALYSIS: A NETWORK META-ANALYSIS OF RANDOMISED CONTROLLED TRIALS (ERA-EDTA 2023) - "Interventions and controls were the following: sevelamer-, bixalomer-, tenapanor-, iron- (ferric citrate, sucroferric oxyhydroxide), calcium-, magnesium-, lanthanum-, aluminium-, nicotinic acid-, and standard treatment or placebo). Our findings from SR based on NMA suggest that lanthanum may attenuate CACS and sevelamer may reduce the risk of all-cause mortality compared to calcium-containing PBs in patients with CKD requiring dialysis."

Retrospective data • Chronic Kidney Disease • Gastrointestinal Disorder • Nephrology • Renal Disease

An update on phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a review of safety profiles. (PubMed, Expert Opin Drug Saf) - "Compared to sevelamer, bixalomer is associated with fewer gastrointestinal symptoms. Aluminum-containing binders, lanthanum carbonate, and sucroferric oxyhydroxide exhibit strong phosphate-lowering activity. Although ferric citrate reduces erythropoiesis-stimulating agents and intravenous iron doses, its use requires monitoring of iron metabolic markers to avoid overload...However, increased pill burden and nonadherence to phosphate binders emerge as new problems. We expect that novel therapeutic strategies will be developed to resolve these issues."

Journal • Review • Chronic Kidney Disease • Gastrointestinal Disorder • Metabolic Disorders • Nephrology • Renal Disease

[VIRTUAL] Successful Treatment of Systemic Calcinosis in a Teenager on Hemodialysis (KIDNEY WEEK 2021) - "Dialytic phosphate (P) clearance, and non-calcium(Ca), non-aluminum(Al) based binder use were maximized, using sevelamer and lanthanum carbonate...After 10 months, iv pamidronate was initiated to prevent further demineralization...Lanthanum is an effective metal Ca binder, but prolonged use may lead to accumulation and systemic deposition. The emergence of new P binders: ferric citrate, sucroferric oxyhydroxide, and bixalomer will offer exciting new treatment options."

Cardiomyopathy • Cardiovascular • Metabolic Disorders • Osteoporosis • Pediatrics • Renal Disease • Rheumatology • Transplantation

The Rising Risk of Chronic Kidney Disease (CKD) and How it is Dealt With: A Review of Current and Potential Phosphate Binders (PB). (PubMed, Mini Rev Med Chem) - "Lanthanum carbonate seemed to lower all-cause mortality and reduce the chance of hypercalcemia, even though a deposit in the GI tract was observed. Colestilan, like sevelamer, lowered LDL cholesterol...Bixalomer appeared to have fewer gastrointestinal side effects than sevelamer. Nano-lanthanum hydroxide and SBR759 may have an interesting future as PBs. In conclusion, the development of new PBs should also take into consideration their potential to function as protection modifiers."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Metabolic Disorders • Nephrology • Renal Disease • FGF23

Multivalent cation and polycation polymer preparations influence pharmacokinetics of dolutegravir via chelation-type drug interactions. (PubMed, Drug Metab Pharmacokinet) - "This study examined how the pharmacokinetics of DTG are affected by co-administration with Al(OH), LaCO, and the polycation polymers bixalomer (Bxl) and sevelamer (Svl)...These comparisons also revealed a considerable reduction in the maximum concentration, suggesting that the interactions of these agents with DTG in the intestinal tract inhibit absorption of DTG. The above results demonstrate that Al(OH), LaCO, Bxl, and Svl affect the pharmacokinetics of DTG and indicate the need for caution when combining any of the above preparations with DTG."

Journal • PK/PD data • Gastrointestinal Disorder

Concurrent administration with multivalent metal cation preparations or polycationic polymer preparations inhibits the absorption of raltegravir via its chelation. (PubMed, J Pharm Pharmacol) - "The interaction of RAL with Al(OH) , LaCO Bxl, or Svl can inhibit RAL absorption into the gastrointestinal tract, and thus, the multivalent metal cation and polycationic polymer are the modifying factors that can affect RAL pharmacokinetics."

Journal • Gastrointestinal Disorder

Astellas submits supplemental New Drug Application for Kiklin capsules, a treatment for hyperphosphatemia, in Japan (Astellas Press Release) - "Astellas Pharma...today announced that it submitted a supplemental new drug application for 'Kiklin® Capsules 250mg (generic name: Bixalomer)' to the Ministry of Health, Labour and Welfare in Japan....The application is based on the results of Phase III studies (the double blind, placebo-controlled study and long term study) in CKD patients on non-dialysis in Japan demonstrated Kiklin® Capsules’ clinical efficacy and a preferable safety profile."

sNDA • Chronic Kidney Disease • Renal Disease

Astellas Pharma launches Kiklin capsules, a treatment for hyperphosphatemia, in Japan (Astellas) - Astellas Pharma announced that Kiklin (bixalomar) capsules 250mg available in Japanese market for indication of hyperphosphatemia in pts on dialysis with CKD; P3 studies in pts on dialysis with CKD in Japan demonstrated Kiklin capsules clinical efficacy in decreasing serum phosphorus concentration, as well as a preferable long-term safety profile; Astellas anticipates that peak sales of Kiklin may reach 7B yen in FY2016

Anticipated drug sales • Launch • Pipeline update • Renal Disease

A Study of Fluoxetine in Major Depressive Disorder (MDD) Long-Term Dosing (clinicaltrials.gov) - P3; N=200; Active, not recruiting; Sponsor: Eli Lilly and Company; Trial primary completion date: Aug 2014 ->Feb 2015

Trial primary completion date • Biosimilar

Phosphorylation Mechanism of Phosphomevalonate Kinase: Implications for Rational Engineering of Isoprenoid Biosynthetic Pathway Enzymes. (PubMed) - J Phys Chem B - "Furthermore, we elucidate that Lys101 functions to neutralize the negative charge developed at the β-, γ-bridging oxygen atom of ATP during phosphoryl transfer. This is the first study on the phosphorylation mechanism of a mevalonate pathway kinase. The elucidation of the catalytic mechanism not only sheds light on the common catalytic mechanism of GHMP kinase superfamily, but also provides the structural basis for engineering the mevalonate pathway kinases to further exploit their applications in the production of a wide range of fine chemicals such as biofuels or pharmaceuticals."

Journal • Biosimilar

Post-marketing Surveillance of Bixalomer in Patients With Pre-dialysis Chronic Kidney Disease (clinicaltrials.gov) - P=N/A; N=100; Recruiting; Sponsor: Astellas Pharma Inc; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Chronic Kidney Disease • Renal Disease

Dose Range-finding Study of ASP1585 in Chronic Kidney Disease Patients on Hemodialysis With Hyperphosphatemia (clinicaltrials.gov) - P2; N=73; Completed; Sponsor: Astellas Pharma Inc

New P2 trial • Biosimilar • Chronic Kidney Disease • Renal Disease

Post-Marketing Surveillance on Long-Term Drug Use of Kiklin (Bixalomer)® Capsules in Patients With Hyperphosphatemia Receiving Peritoneal Dialysis (clinicaltrials.gov) - P=N/A; N=123; Completed; Sponsor: Astellas Pharma Inc; Active, not recruiting ➔ Completed

Trial completion

A Study to Evaluate LY01011 and Xgeva® in Healthy Adults (clinicaltrials.gov) - P1; N=168; Not yet recruiting; Sponsor: Luye Pharma Group Ltd.

Clinical • New P1 trial

Regional prescription surveillance of phosphate binders in the western Saitama area: the substantial role of ferric citrate hydrate in improving serum phosphorus levels and erythropoiesis. (PubMed, Clin Exp Nephrol) - "This regional survey suggests that serum phosphorus is well managed and that FeC has the potential to reduce the serum phosphorus level relative to other PBs and to ameliorates anemia."

Journal

Phosphate binders in chronic kidney disease: an updated narrative review of recent data. (PubMed, J Nephrol) - "For this narrative review a PubMed searched was undertaken to identify new publications on phosphate binders that had been published between January 2015 and July 2019. The present review summarizes this most recent information on dietary measures and their problems in treating hyperphosphatemia in CKD patients, overall effects of phosphate binders on cardiovascular mortality and morbidity, adherence to phosphate binder therapy as well as new data on specific aspects of the various phosphate binders on the market: calcium-containing phosphate binders, polymeric phosphate binders (sevelamer, bixalomer, colestilan), magnesium-containing phosphate binders, lanthanum carbonate, ferric citrate, sucroferric oxyhydroxide, and new compounds in development, in particular drugs targeting intestinal phosphate transporters."

Journal • Review

Post-marketing Surveillance of Bixalomer in Patients With Pre-dialysis Chronic Kidney Disease (clinicaltrials.gov) - P=N/A; N=144; Completed; Sponsor: Astellas Pharma Inc; Active, not recruiting ➔ Completed

Clinical • Trial completion

Post-Marketing Surveillance on Long-Term Drug Use of Kiklin (Bixalomer)® Capsules in Patients With Hyperphosphatemia Receiving Peritoneal Dialysis (clinicaltrials.gov) - P=N/A; N=123; Active, not recruiting; Sponsor: Astellas Pharma Inc; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed