AVGEMSI (Gemcitabine) Injection

AVGEMSI (gemcitabine) is a nucleoside analog antineoplastic agent supplied as a ready-to-dilute sterile solution for intravenous infusion at a concentration of 38 mg/mL. It is held under NDA 219920 by Avyxa Holdings, LLC, approved in June 2025 under the 505(b)(2) pathway, with an initial U.S. approval for gemcitabine dating to 1996.

NDA 219920 (Avgemsi (gemcitabine) injection) was submitted and approved under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The sponsor is Avyxa Holdings, LLC, and the application was approved on June 27, 2025. The product is a ready-to-use solution supplied as gemcitabine injection 200 mg/5.26 mL, 1 g/26.3 mL, and 2 g/52.6 mL (38 mg/mL) in a multiple-dose vial for intravenous use. The current NDA 219920 is indicated, in combination with carboplatin, for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy; in combination with paclitaxel, for first-line treatment of metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated; in combination with cisplatin, for the first-line treatment of inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer; and as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas.

Gemcitabine has been the subject of prior new drug applications. NDA 020509 (Gemzar) is a sterile lyophilized powder for injection supplied in 200 mg and 1 g single-dose vials for intravenous use, with an initial U.S. approval in 1996, indicated in ovarian cancer (with carboplatin), metastatic breast cancer (with paclitaxel), non-small cell lung cancer (with cisplatin), and pancreatic cancer. NDA 208313 (Infugem) is a premixed, ready-to-use gemcitabine in 0.9% sodium chloride injection, 10 mg/mL, supplied as single-dose intravenous infusion bags, with the same gemcitabine oncology indications. The current NDA 219920 differs from these prior applications principally in formulation and presentation: it is a ready-to-use aqueous solution at 38 mg/mL supplied in multiple-dose vials requiring dilution prior to infusion, as distinguished from the Gemzar lyophilized powder that requires reconstitution and from the Infugem fixed-dose premixed infusion bags. The active ingredient, intravenous route, and approved indications are the same as those of the reference listed drug.

The prescribing information for the current NDA 219920 does not report any new clinical, bioavailability, or bioequivalence studies conducted to support the 505(b)(2) filing. The Clinical Studies section of the labeling describes only the efficacy trials of the reference gemcitabine product across the ovarian, breast, non-small cell lung, and pancreatic cancer indications, and the Clinical Pharmacology section presents the established gemcitabine pharmacokinetic data; no AVGEMSI-specific clinical, BA, BE, or PK study is described.

The Orange Book does not list any exclusivity for the current NDA 219920.

AVGEMSI is indicated for the following:

• In combination with carboplatin for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.
• In combination with paclitaxel for first-line treatment of metastatic breast cancer following failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.
• In combination with cisplatin for first-line treatment of inoperable, locally advanced or metastatic non-small cell lung cancer (NSCLC).
• As first-line monotherapy for locally advanced or metastatic pancreatic adenocarcinoma, including patients previously treated with fluorouracil.

AVGEMSI is supplied as an injection solution in multiple-dose vials at a concentration of 38 mg/mL. Available presentations include 200 mg/5.26 mL, 1 g/26.3 mL, and 2 g/52.6 mL. The solution is clear and colorless to light straw-colored.

Per mL: Gemcitabine 38 mg (present as gemcitabine hydrochloride; equivalent to 38 mg gemcitabine free base per mL)

Water for injection and sodium hydroxide (for pH adjustment). Specific quantities of inactive ingredients were not provided in the reviewed labeling.

AVGEMSI is administered as a 30-minute intravenous infusion following dilution.

Ovarian Cancer

1,000 mg/m² administered on Days 1 and 8 of each 21-day cycle, in combination with carboplatin (administered on Day 1 after AVGEMSI).

Breast Cancer

1,250 mg/m² on Days 1 and 8 of each 21-day cycle, in combination with paclitaxel (administered on Day 1 prior to AVGEMSI).

Non-Small Cell Lung Cancer (NSCLC)

Either 1,000 mg/m² on Days 1, 8, and 15 of each 28-day cycle, or 1,250 mg/m² on Days 1 and 8 of each 21-day cycle, in combination with cisplatin (administered on Day 1 after AVGEMSI).

Pancreatic Cancer

1,000 mg/m² weekly for 7 consecutive weeks followed by 1 week of rest, then continuing on Days 1, 8, and 15 of each subsequent 28-day cycle.

The calculated dose is withdrawn from the vial and diluted with 0.9% Sodium Chloride Injection to a minimum final concentration of 0.1 mg/mL. Diluted solution may be stored at 20°C to 25°C for no more than 24 hours and must be discarded if not used within that period. Following the first vial puncture, partially used multiple-dose vials should be stored refrigerated in the original carton for up to 14 days; any unused portion must be discarded thereafter. AVGEMSI is a hazardous drug and requires appropriate handling and disposal procedures.

AVGEMSI is supplied as a sterile solution in multiple-dose vials (200 mg/5.26 mL, 1 g/26.3 mL, and 2 g/52.6 mL), individually packaged in cartons.

Unopened vials should be stored refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze. The approved expiry dating period is 18 months from the date of manufacture when stored under recommended conditions.

The content below is an abbreviated summary drawn from the full prescribing information. It is meant to give a directional overview and should not be relied upon as comprehensive. Consult the full label for complete details.

The pharmacokinetic data presented in labeling reflect gemcitabine administered intravenously and are not specific to the AVGEMSI formulation. Gemcitabine exhibits linear pharmacokinetics in patients with solid tumors, consistent with a two-compartment model. Volume of distribution increases with longer infusion durations, and plasma protein binding is negligible. Disposition of a radiolabeled dose was predominantly urinary, occurring within one week, with excretion primarily as the inactive uracil metabolite (dFdU) and a minor fraction as parent gemcitabine.

Half-life is markedly influenced by infusion duration, ranging from 42 to 94 minutes for short infusions and from 245 to 638 minutes for long infusions, consistent with the substantially increased volume of distribution observed with prolonged administration. The intracellular active metabolite gemcitabine triphosphate has a half-life of 1.7 to 19.4 hours in peripheral blood mononuclear cells.

Gemcitabine clearance is influenced by both age and sex. Geriatric patients exhibit reduced clearance, resulting in proportionally higher plasma concentrations at any given dose. Female patients similarly demonstrate lower clearance and prolonged half-lives relative to male patients. These demographic differences should be considered when evaluating individual exposure and tolerability.

The content below is an abbreviated summary drawn from the full prescribing information. It is meant to give a directional overview and should not be relied upon as comprehensive. Consult the full label for complete details.

Clinical efficacy for the approved indications is supported by the established gemcitabine evidence base referenced in the labeling, reflecting the drug's history of U.S. approval since 1996. Supporting studies include a randomized trial in relapsed ovarian cancer comparing gemcitabine plus carboplatin versus carboplatin alone; trials in metastatic breast cancer evaluating gemcitabine combined with paclitaxel; a randomized NSCLC trial comparing gemcitabine plus cisplatin versus etoposide plus cisplatin; and pancreatic cancer studies establishing the role of gemcitabine monotherapy. These studies are not specifically identified as having been conducted with the NDA 219920 AVGEMSI presentation.