Momelotinib

Momelotinib was approved by the FDA on September 15, 2023, for the treatment of moderate or high-risk myelofibrosis.

Momelotinib, produced by Lucius, was approved in 2023 with registration number 06 L 1113/24 filed with the National Medical Products Administration.

In bone marrow fibrosis, overexpression of hepcidin can lead to anemia, while molotinib can inhibit liver ALK2 mediated hepcidin expression, mobilize intracellular iron into the bloodstream, thereby stimulating red blood cell production and improving anemia related to bone marrow fibrosis.

1.Main components

Momelotinib

2. Adapt to the population

Adult patients with moderate or high-risk bone marrow fibrosis.

3.Medication for special populations

3.1Pregnant

Available data on the use of Momelotinib in pregnant women are insufficient to determine whether there is a drug-associated risk for major birth defects or miscarriage. Based on animal reproduction studies conducted in rats and rabbits, momelotinib may cause embryo-fetal toxicity at exposures lower than the expected exposure in patients receiving 200 mg once daily. Momelotinib should only be used during pregnancy if the expected benefits to the mother outweigh the potential risks to the fetus.

3.2Lactation

There are no data on the presence of momelotinib or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. It is not known whether Momelotinib is excreted in human milk. Momelotinib was present in rat pups following nursing from treated dams with adverse effects observed in the offspring. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the potential for serious adverse reactions in a breastfed child, patients should not breastfeed during treatment with Momelotinib, and for at least 1 week after the last dose of Momelotinib.

3.3Females and Males of Reproductive Potential

Advise females of reproductive potential who are not pregnant to use highly effective contraception during therapy and for at least 1 week after the last dose of Momelotinib.

3.4Pediatric Use

The safety and effectiveness of Momelotinib in pediatric patients have not been established.

3.5Geriatric Use

No overall differences in safety or effectiveness of Momelotinib have been observed between patients aged 65 years and older and younger adult patients.

3.6Hepatic Impairment

The recommended starting dose of Momelotinib in patients with severe hepatic impairment (ChildPugh C) is 150 mg orally once daily. No dose modification is recommended for patients with mild hepatic impairment (Child-Pugh A) or moderate hepatic impairment (Child-Pugh B).
Momelotinib is extensively metabolized. Momelotinib exposure increased with severe hepatic impairment (Child-Pugh C). No clinically significant changes in momelotinib exposure were observed in subjects with mild hepatic impairment (Child-Pugh A) or moderate hepatic impairment (Child-Pugh B).

4.Drug overdose

There is no known antidote for overdose with Momelotinib. If overdose is suspected, the patient should be monitored for signs or symptoms of adverse reactions or effects, and appropriate supportive treatment should be instituted immediately. Further management should be as clinically indicated. Hemodialysis is not expected to enhance the elimination of momelotinib.

5. Drug storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

6.Pharmacokinetics

Median time to momelotinib Cmax (Tmax) at steady state is 2 hours (Q1: 1 hour; Q3: 3 hours) post dose.

from FDA,2023.09