Maralixibat: First Approval

Shirley, Matt

doi:10.1007/s40265-021-01649-0

Cited by 36 publications

(18 citation statements)

References 8 publications

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“…Oral administration of maralixibat induces clinically meaningful improvements in cholestasis (Gonzales et al 2021 ). It can cause serious AEs such as liver test abnormalities, fat-soluble vitamin deficiency, and some common AEs including diarrhea, abdominal pain, and vomiting (Shirley 2022 ).…”

Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition (“first-in-indication”), (2) first drug using a novel molecular mechanism (“first-in-class”), and (3) “next-in-class”, i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indication drugs. By treatment area, the largest group is once again cancer drugs, many of which target specific genetic alterations. Every second drug approved in 2021 targets an orphan disease, half of them being cancers. Small molecules continue to dominate new drug approvals, followed by antibodies and non-antibody biopharmaceuticals. In 2021, the FDA continued to approve drugs without strong evidence of clinical effects, best exemplified by the aducanumab controversy.

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Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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“…ASBT inhibitors improved cholestatic injury in mice [ 194 , 195 ] and cholestatic pruritus in PBC patients [ 196 ]. The ASBT inhibitor maralixibat was recently approved for the treatment of cholestatic pruritus in patients with Alagille syndrome [ 197 ], whereas trials for other cholestatic disorders are ongoing [ 198 , 199 ]. The most common side effects were diarrhea and abdominal pain.…”

Section: Bile Acid–related Treatments In Cholestatic Liver Diseasesmentioning

confidence: 99%

“…The most common side effects were diarrhea and abdominal pain. The deficiency of fat-soluble vitamins, which require bile acids for intestinal absorption, was also reported [ 196 , 197 ]. Besides bile acid–binding resins and ASBT inhibition, inhibition of hepatic NTCP may reduce bile acid uptake by hepatocytes.…”

Section: Bile Acid–related Treatments In Cholestatic Liver Diseasesmentioning

confidence: 99%

Bile acids and their receptors: modulators and therapeutic targets in liver inflammation

2022

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Bile acids participate in the intestinal emulsion, digestion, and absorption of lipids and fat-soluble vitamins. When present in high concentrations, as in cholestatic liver diseases, bile acids can damage cells and cause inflammation. After the discovery of bile acids receptors about two decades ago, bile acids are considered signaling molecules. Besides regulating bile acid, xenobiotic, and nutrient metabolism, bile acids and their receptors have shown immunomodulatory properties and have been proposed as therapeutic targets for inflammatory diseases of the liver. This review focuses on bile acid–related signaling pathways that affect inflammation in the liver and provides an overview of the preclinical and clinical applications of modulators of these pathways for the treatment of cholestatic and autoimmune liver diseases.

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“…Maralixibat has also been evaluated in PBC and PSC, but clinical trials were discontinued because this treatment did not improve pruritus compared to placebo [ 60 ]. Recently, maralixibat was approved for clinical use for ALGS patients by the FDA [ 61 ]. However, its use for other cholestatic diseases, such as PFIC1-4, is currently under evaluation by the EMA [ 62 ].…”

Section: Current Treatmentsmentioning

confidence: 99%

Gene Therapy for Acquired and Genetic Cholestasis

Martínez-García

Molina

González‐Aseguinolaza

et al. 2022

Biomedicines

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Cholestatic diseases can be caused by the dysfunction of transporters involved in hepatobiliary circulation. Although pharmacological treatments constitute the current standard of care for these diseases, none are curative, with liver transplantation being the only long-term solution for severe cholestasis, albeit with many disadvantages. Liver-directed gene therapy has shown promising results in clinical trials for genetic diseases, and it could constitute a potential new therapeutic approach for cholestatic diseases. Many preclinical gene therapy studies have shown positive results in animal models of both acquired and genetic cholestasis. The delivery of genes that reduce apoptosis or fibrosis or improve bile flow has shown therapeutic effects in rodents in which cholestasis was induced by drugs or bile duct ligation. Most studies targeting inherited cholestasis, such as progressive familial intrahepatic cholestasis (PFIC), have focused on supplementing a correct version of a mutated gene to the liver using viral or non-viral vectors in order to achieve expression of the therapeutic protein. These strategies have generated promising results in treating PFIC3 in mouse models of the disease. However, important challenges remain in translating this therapy to the clinic, as well as in developing gene therapy strategies for other types of acquired and genetic cholestasis.

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Maralixibat: First Approval

Cited by 36 publications

References 8 publications

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Bile acids and their receptors: modulators and therapeutic targets in liver inflammation

Gene Therapy for Acquired and Genetic Cholestasis

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