KRESLADI Suspension for infusion Ref.[116648] Active ingredients: Marnetegragene autotemcel

5.1 Serious Infections

Serious infections have occurred with KRESLADI administration [see Adverse Reactions (6.1)]. Increased susceptibility to infections may occur due to administration of myeloablative conditioning prior to KRESLADI infusion.

Monitor patients for signs and symptoms of infection before and after KRESLADI infusion and treat appropriately. Administer prophylactic antimicrobials according to institutional guidelines.

Avoid administration of KRESLADI in patients with active bloodstream infections or other serious, untreated infections.

Any blood products required after KRESLADI infusion should be irradiated.

5.2 Veno-Occlusive Disease

Veno-occlusive disease has occurred with KRESLADI treatment [see Adverse Reactions (6.1)]. Increased susceptibility to veno-occlusive disease may occur due to administration of myeloablative conditioning prior to KRESLADI infusion. Monitor patients for signs and symptoms of veno-occlusive disease including assessment of liver function tests during the first month following KRESLADI infusion.

5.3 Neutrophil Engraftment Failure

Neutrophil engraftment failure may occur after treatment with KRESLADI. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥500 cells/microliter obtained on different days by Day 43 after infusion of KRESLADI. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with KRESLADI, provide rescue treatment with the back-up collection of CD34+ cells [see Preparation Before KRESLADI Infusion (2.2)].

5.4 Delayed Platelet Engraftment

Delayed platelet engraftment may occur after treatment with KRESLADI. Monitor platelet counts and bleeding until platelet engraftment and platelet recovery are achieved.

5.5 LVV-Mediated Insertional Oncogenesis

Lentiviral vector (LVV)-mediated insertional oncogenesis may occur after treatment with KRESLADI. Hematologic malignancy is a lifelong risk and patients treated with KRESLADI may develop hematologic malignancy at any time following treatment.

Monitor for hematologic malignancies clinically, and with a complete blood count (with differential) at least annually and integration site analysis as warranted for at least 15 years after treatment with KRESLADI and as clinically indicated. If malignancy is detected in any patient who received KRESLADI, contact Rocket Pharmaceuticals, Inc. at 1-800-982-2410 for reporting and to obtain instructions on collection of samples for testing.

5.6 Hypersensitivity Reactions

Hypersensitivity reactions including anaphylaxis may occur with the infusion of KRESLADI. The dimethyl sulfoxide (DMSO) in KRESLADI may cause hypersensitivity reactions which may occur in patients with and without prior exposure to DMSO.

Monitor patients for signs and symptoms of hypersensitivity reactions during and after KRESLADI infusion. If a hypersensitivity reaction occurs, pause infusion if ongoing and manage according to clinical practice.

5.7 Anti-retroviral Use

Anti-retroviral medications may interfere with manufacturing of KRESLADI [see Drug Interactions (7.2)]. If a patient requires anti-retrovirals for HIV prophylaxis, mobilization and apheresis of CD34+ cells for KRESLADI manufacturing should be delayed until HIV infection is adequately ruled out. Patients should not take anti-retroviral medications for at least one month prior to mobilization, or for the expected duration required for the elimination of the anti-retroviral medications, and until all cycles of apheresis are completed.

5.8 Interference with Serology Testing

Patients who have received KRESLADI are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to LVV provirus insertion resulting in a false-positive test for HIV. Therefore, patients who have received KRESLADI should not be screened for HIV infection using a PCR-based assay.

5.9 Blood, organ, tissue and cell donation

Patients treated with KRESLADI should not donate blood, organs, tissues, or cells for transplantation at any time in the future.

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 KRESLADI in one clinical study (Study RP-L201-0318). A total of 9 pediatric patients with severe LAD-I received a single dose of intravenous KRESLADI with a median dose of 4.3 × 10 ⁶ CD34+ cells/kg (range: 2.8 to 10 CD34+ cells/kg) [see Clinical Studies (14)]. The median duration of follow up after KRESLADI 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 KRESLADI 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

No formal drug interaction studies have been performed. KRESLADI is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters.

7.1 Vaccines

The safety and effectiveness of immunization with live viral vaccines during or following KRESLADI treatment has not been studied. Vaccination is not recommended during the 6 weeks preceding the start of myeloablative conditioning, and until hematological recovery following treatment with KRESLADI. Where feasible, administer childhood vaccinations prior to myeloablative conditioning for KRESLADI.

7.2 Anti-retroviral Use

Patients should not take anti-retroviral medications for at least one month prior to initiating medications for stem cell mobilization and for the expected duration for elimination of the medications, and until all cycles of apheresis are completed [see Warnings and Precautions (5.6)]. Anti-retroviral medications may interfere with manufacturing of KRESLADI.

Risk Summary

There are no available data from KRESLADI administration in pregnant women.

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

No nonclinical germline transmission studies have been conducted with KRESLADI.

KRESLADI 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.

Risk Summary

There is no available data regarding the presence of KRESLADI 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 KRESLADI and any potential adverse effects on the breastfed child from KRESLADI or from the underlying maternal condition.

Pregnancy Testing

A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before administration of KRESLADI in females of childbearing potential.

Contraception

There are insufficient exposure data to provide a precise recommendation on duration of contraception following treatment with KRESLADI. Consult the Prescribing Information of the mobilization and conditioning agents for information on the need for effective contraception.

Infertility

There are no data on the effects of KRESLADI on fertility. Data are available on the risk of infertility with myeloablative conditioning. Advise patients of the option to cryopreserve semen or ova before treatment, if appropriate.

The safety and efficacy of KRESLADI have been established in pediatric patients with severe LAD-I. The use of KRESLADI in the pediatric population was supported by one clinical study which treated 9 patients 9.8 months to 9.8 years of age [see Adverse Reactions (6) and Clinical Studies (14)].

The safety and effectiveness of KRESLADI has not been established in geriatric patients. Clinical studies of KRESLADI for this indication did not include patients aged 65 years and over.

8.6 Patients Seropositive for Human Immunodeficiency Virus (HIV)

KRESLADI has not been studied in patients with HIV-1, HIV-2, HTLV-1, or HTLV-2. A negative serology test for HIV is necessary to ensure acceptance of apheresis material for KRESLADI manufacturing. Apheresis material from patients with a positive test for HIV will not be accepted for KRESLADI manufacturing.