FDA Accepts NDA for Pemetrexed Injection in NSCLC, Mesothelioma

Following pembrolizumab and prior to platinum chemotherapy, the recommended dosage of Pemrydi RTU is 500 mg/m² delivered intravenously over 10 minutes on the first day of each 21-day cycle.

The FDA has accepted the 505(b)(2) new drug application (NDA) for Pemrydi RTU, a ready-to-use, injectable formulation of pemetrexed employed as a treatment for metastatic, non-squamous non–small cell lung cancer (NSCLC) and malignant pleural mesothelioma, according to a press release from Amneal Pharmeceuticals.¹

Pemrydi RTU is the first agent of its kind, and does not need to be reconstituted, diluted, or refrigerated, in addition to being ready-to-use.

When combined with pembrolizumab (Keytruda) and platinum chemotherapy, the injection can be act as an initial treatment for patients with metastatic, non-squamous NSCLC whose disease expresses no EGFR or ALK genomic tumor aberrations. Pemrydi RTU may also have use in patients with locally-advanced or metastatic disease as a single agent or in combination with cisplatin. According to the package insert, patients in this population who experienced no disease progression following 4 cycles of frontline, platinum-based chemotherapy can also receive the injectable as maintenance therapy.²

Additionally, when combined with cisplatin, the injection can act as an initial treatment for patients with malignant pleural mesothelioma whose disease is unresectable or who are ineligible for curative therapy.

The agent will be available in a vial size of either 100 mg/10 mL, 500 mg/50 mL, or 1000 mg/100 mL.

“We believe Pemrydi RTU, the first ready-to-use version of a key oncology injectable, will offer a meaningful advantage in this improved presentation,” Harsher Singh, senior vice president at Amneal Biosciences, said in the press release.¹ “By eliminating formulation steps common with other pemetrexed products, we are improving provider efficiencies while reducing the risk for medication errors.”

Following pembrolizumab and prior to platinum chemotherapy, the recommended dosage of Pemrydi RTU is 500 mg/m² delivered intravenously over 10 minutes on the first day of each 21-day cycle. The dosing guidelines are the same when administering the injection in combination with cisplatin or as a single agent.

The recommended accompanying agents include 4 mg of oral dexamethasone delivered twice daily on the day before, the day of, and the day after Pemrydi RTU dosing.² Care providers should also administer oral folic acid at a dose of 400 mcg to 1000 mcg once daily, beginning 7 days prior to the first dose of the injectable and continuing until 21 days after the last dose of the injectable. Intramuscular vitamin B12 deliveredat a dose of 1 mg a week prior to the first injectable dose and every 3 cycles thereafter is also recommended.

Pemrydi RTU can cause severe myelosuppression resulting in cytopenia and an increased risk of infection, and should not be administered in patients with an absolute neutrophil count lower than 1500 cells/mm³ and a platelet count lower than 100,000 cells/mm³, according to the package insert.² The injectable should also not be used to treat patients with a creatinine clearance lower than 45 mL per minute, as it can cause severe or fatal renal failure.

The most frequent adverse effects (AEs) associated with Pemrydi RTU as a single agent include fatigue, nausea, and anorexia. In combination with cisplatin, the most frequent AEs are vomiting, neutropenia, anemia, stomatitis/pharyngitis, thrombocytopenia, and constipation. In combination with pembrolizumab and platinum chemotherapy, the most frequent AEs are fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, and pyrexia.

Patients should discontinue treatment with the injectable in cases of severe or life-threatening, bullous, blistering, or exfoliating skin toxicity; confirmed interstitial pneumonitis; radiation recall; or embryo-fetal toxicity.

References

1. Amneal receives 505(b)(2) NDA approval from FDA for PEMRYDI RTU®, a ready-to-use oncology injectable. News release. Amneal Pharmaceuticals, Inc. June 14, 2023. Accessed June 15, 2023. https://bit.ly/42CdhCc
2. Pemrydi-RTU. Package insert. Amneal Pharmaceuticals, Inc. Accessed June 15. 2023. bit.ly/45YKiLI