FDA Expands Methotrexate Approval to Include Pediatric ALL and pJIA
核心洞察
The FDA has broadened the approval of methotrexate to include pediatric patients with acute lymphoblastic leukemia (搜索) (ALL) and polyarticular juvenile idiopathic arthritis (搜索) (pJIA).
This methotrexate formulation is now the only commercially available liquid solution for both pediatric and adult indications, offering a patient-friendly alternative.
The oral solution, designed with an orange flavor and a dedicated dosing syringe, remains stable at room temperature for 90 days, enhancing convenience for patients.
The FDA has expanded the approval of methotrexate to include pediatric patients with acute lymphoblastic leukemia (搜索) (ALL) and polyarticular juvenile idiopathic arthritis (搜索) (pJIA), according to Shorla Oncology (搜索), the drug's developer. This decision marks a significant step forward in addressing the unmet needs of pediatric care in oncology and autoimmune diseases.
Following this approval, the methotrexate formulation becomes the only commercially available liquid methotrexate solution for both pediatric and adult indications. The availability of a liquid formulation is particularly beneficial for pediatric patients who may have difficulty swallowing pills.
The methotrexate formulation is designed as an orally available anti-inflammatory solution for patients with oncological, dermatological, and rheumatological diseases. It features an orange flavor and is packaged with a dedicated dosing syringe, eliminating the need for crushing or splitting pills. The solution remains stable at room temperature for 90 days without requiring cold chain storage pre-dispense, adding convenience for patients and healthcare providers.
Benefits of the New Formulation
"For patients with chronic conditions including cancer, methotrexate offers a convenient, palatable option for patients who may have difficulty swallowing pills," said Orlaith Ryan, chief technical officer and co-founder of Shorla Oncology (搜索). "At Shorla, we are committed to continuity of supply of age-appropriate formulations for patients in need."
The FDA originally approved methotrexate for multiple adult indications in November 2022. These indications include ALL in combination with chemotherapy maintenance, mycosis fungoides (搜索) as monotherapy or in combination with chemotherapy, relapsed/refractory non-Hodgkin lymphoma (搜索) as part of a metronomic chemotherapy regimen, rheumatoid arthritis (搜索), and severe psoriasis (搜索). The commercial launch of methotrexate across the United States was announced in December 2023.
Important Safety Information
A boxed warning for methotrexate indicates the risk of potential embryo-fetal toxicity, hypersensitivity reactions, and severe adverse reactions. The agent is contraindicated as treatment for non-neoplastic diseases in pregnant women and those with a history of severe hypersensitivity reactions. Common toxicities reported with methotrexate include ulcerative stomatitis, leukopenia, nausea, and abdominal distress.
Methotrexate plasma concentration elevations, which may increase the risk of severe adverse reactions, can occur when the solution is administered in combination with products such as oral antibiotics, antifolate drugs, nonsteroidal anti-inflammatory drugs, hepatoxic agents, highly protein-bound drugs, proton pump inhibitors, and weak acids. Administering methotrexate in combination with nitrous oxide anesthesia may increase the likelihood of severe adverse reactions due to heightened effects on folate-dependent metabolic pathways. Sequencing methotrexate with folic acid or any derivates may limit the clinical efficacy of the oral solution among those with neoplastic diseases.
Convenient Features
"In addition to its palatable formulation, methotrexate offers key differences over similar drugs, such as room temperature stability for 3 months after opening, which eliminates the need for refrigeration before dispensing and adds convenience for patients," said Rayna Herman, chief commercial officer at Shorla Oncology (搜索).