Marnetegragene autotemcel

There are no available data from marnetegragene autotemcel administration in pregnant women.

No animal reproductive and developmental toxicity studies have been conducted to assess whether marnetegragene autotemcel can cause fetal harm when administered to a pregnant woman.

No nonclinical germline transmission studies have been conducted with marnetegragene autotemcel.

Marnetegragene autotemcel must not be administered during pregnancy because of the risk associated with conditioning.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

There is no available data regarding the presence of marnetegragene autotemcel in human milk, the effect on the breastfed infant, and the effects on milk production. Because of the potential risks associated with myeloablative conditioning, discontinue breastfeeding during conditioning. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for marnetegragene autotemcel and any potential adverse effects on the breastfed child from marnetegragene autotemcel or from the underlying maternal condition.

No carcinogenicity studies have been performed with marnetegragene autotemcel.

Intravenous administration of marnetegragene autotemcel in a mouse model of LAD-I and intravenous administration of marnetegragene autotemcel manufactured from healthy donors in immunodeficient mice showed no evidence of toxicity, genotoxicity, or oncogenesis (tumorigenicity).

No studies have been conducted to evaluate the effects of marnetegragene autotemcel on fertility.

As clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety data described in this section reflect exposure to marnetegragene autotemcel in one clinical study (Study RP-L201-0318). A total of 9 pediatric patients with severe LAD-I received a single dose of intravenous marnetegragene autotemcel with a median dose of 4.3 × 10 ⁶ CD34+ cells/kg (range: 2.8 to 10 CD34+ cells/kg). The median duration of follow up after marnetegragene autotemcel administration was 4.2 years (range: 3.6 to 5.7 years).

Serious adverse reactions were reported in 4 patients (44%) including serious infections (n=4), pulmonary arterial hypertension (n=1), sensorineural deafness (n=1), and veno-occlusive disease (n=1).

Table 1 presents the most common adverse reactions reported in Study RP-L201-0318.

Table 1. Non-Laboratory Adverse Reactions Reported in ≥20% of Patients in Study RP-L201-0318 (N=9):

Note: Adverse reactions are defined as adverse events that occurred from myeloablative conditioning administration through year 2 following marnetegragene autotemcel administration.
^* Includes multiple related terms
^† Device-related infection includes vascular device infection, device related bacteremia, and bacteremia that occurred with a central line in place
^‡ Skin lesion includes pyoderma gangrenosum, skin lesion, aseptic pustule, lip erythema, hand erythema, skin erythema at port site, and skin hyperpigmentation
^§ Rash includes rash, eczema, atopic dermatitis and diaper dermatitis

Table 2 presents laboratory abnormalities that worsened from baseline in ≥20% of patients in Study RP-L201-0318.

Table 2. Laboratory Abnormalities that Worsened from Baseline Reported in ≥20% of Patients in Study RP-L201-0318 (N=9)*:

^* Baseline laboratory values were assessed prior to myeloablative conditioning
^† All events occurred within 30 days post-infusion except for liver enzymes increased, which occurred in 3 patients within 30 days and in one patient after 90 days post-infusion