FDA Expands Approval for Methotrexate in Pediatric ALL, pJIA Indications
The expanded approval of methotrexate may offer a convenient alternative to pediatric patients who have difficulty swallowing pills.
Developers designed the methotrexate formulation as an anti-inflammatory, orally available solution for use among patients with oncological, dermatological, and rheumatological diseases. The agent has an orange flavor and is packaged with a dedicated dosing syringe, which may eliminate the need for crushing or splitting pills.
The FDA has expanded approval status of methotrexate to include pediatric patients who have acute lymphoblastic leukemia (ALL) or polyarticular juvenile idiopathic arthritis (pJIA), according to a press release from the developer, Shorla Oncology.1
Following the FDA’s decision, this methotrexate formulation is now the only commercially available liquid methotrexate solution for both pediatric and adult indications.
“This approval follows [methotrexate’s] successful use in adult patients and represents a critical step forward in addressing the unmet needs of pediatric care in oncology and autoimmune diseases,” Sharon Cunningham, chief executive officer at Shorla Oncolgoy, stated in the press release.1 “We are pleased to offer a convenient, patient-friendly alternative for both adult and pediatric patients in the [United States] as we continue to develop innovative solutions for those with limited treatment options.”
Developers designed the methotrexate formulation as an anti-inflammatory, orally available solution for use among patients with oncological, dermatological, and rheumatological diseases. The agent has an orange flavor and is packaged with a dedicated dosing syringe, which may eliminate the need for crushing or splitting pills. Additionally, the solution can remain stable at room temperature for 90 days without requiring a cold chain storage pre-dispense.
“For patients with chronic conditions including cancer, [methotrexate] offers a convenient, palatable option for patients who may have difficulty swallowing pills. At Shorla, we are committed to continuity of supply of age-appropriate formulations for patients in need,” Orlaith Ryan, chief technical officer and co-founder of Shorla Oncology, stated in the press release.1
The FDA originally approved methotrexate for multiple adult indications in November 2022.2 Specifically, the oral solution was indicated for those with ALL in combination with chemotherapy maintenance, mycosis fungoides as monotherapy or in combination with chemotherapy, relapsed/refractory non-Hodgkin lymphoma as part of a metronomic chemotherapy regimen, rheumatoid arthritis, and severe psoriasis.
Developers subsequently announced the commercial launch of methotrexate across the United States in December 2023.3
“We are delighted to introduce [methotrexate] as an alternative treatment option for patients who may have difficulty swallowing pills….Today's announcement is another significant advancement in our pipeline and our mission to bring new therapeutic options to patients in need,” Cunningham stated at the time of the product’s commercial launch.3
A boxed warning for methotrexate indicates the risk of potential embryo-fetal toxicity, hypersensitivity reactions, and severe adverse reactions. Additionally, the agent is contraindicated as treatment for non-neoplastic diseases in women who are pregnant and for those who have 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.
“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,” Rayna Herman, chief commercial officer at Shorla Oncology, concluded.1
References
- Shorla Oncology announces U.S. Food and Drug Administration (FDA) expanded approval of JYLAMVO™ (methotrexate), an oncology and autoimmune drug for pediatric indications. News release. Shorla Oncology. October 29, 2024. Accessed October 29, 2024. https://tinyurl.com/33up3fnd
- Jylamvo® (methotrexate) – New drug approval. Optum Rx. Accessed October 29, 2024. https://tinyurl.com/36xpn8pa
- Shorla Oncology & EVERSANA announce U.S. commercial launch of FDA-approved JYLAMVO, the first and only oral methotrexate solution approved in the U.S. for adults. News release. Shora Oncology. December 19, 2023. Accessed October 29, 2024. https://tinyurl.com/msxrp8au
