Remestemcel-L-Rknd

FDA Drug Information • Also known as: Ryoncil

Brand Names: Ryoncil
Dosage Form: KIT
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION RYONCIL is provided as a frozen cell suspension in a cryogenic vial. The active ingredient in RYONCIL is comprised of culture-expanded mesenchymal stromal cells (MSCs) isolated from the bone marrow of healthy human adult donors. Each cryovial contains nominally 25 x 10 6 MSCs in 3.8 mL (a target concentration 6.68 x 10 6 cells/mL) formulated in Plasma Lyte ® -A (70% v/v), Human Serum Albumin (HSA) Solution (25%) (20% v/v) and Dimethyl sulfoxide (DMSO) (10% v/v). The product is thawed and combined with Plasma-Lyte ® A prior to intravenous administration.

What Is Remestemcel-L-Rknd Used For?

1 INDICATIONS AND USAGE RYONCIL is indicated for the treatment of steroid refractory acute graft versus host disease (SR-aGvHD) in pediatric patients 2 months of age and older. RYONCIL is an allogeneic bone marrow-derived mesenchymal stromal cell (MSC) therapy indicated for the treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients 2 months of age and older.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For intravenous use only. For intravenous use only. The recommended dosage of RYONCIL is 2 × 10 6 MSC/kg body weight per intravenous infusion given twice per week for 4 consecutive weeks. Infusions should be administered at least 3 days apart. Assess response 28 ± 2 days after the first dose and administer further treatment as appropriate as described in the table below. Recommended Treatment Based on Day 28 Response Response Recommendation Complete Response (CR) No further treatment with RYONCIL Partial or Mixed Response Repeat administration of RYONCIL once a week for additional 4 weeks (4 infusions total) No Response Consider alternative treatments Recurrence of GvHD after CR Repeat administration of RYONCIL twice a week for an additional 4 consecutive weeks (8 infusions total) 2.1 Recommended Dosage The recommended dosage of RYONCIL is 2 × 10 6 mesenchymal stromal cells (MSC)/kg body weight per intravenous infusion given twice a week for 4 consecutive weeks for a total of 8 infusions. Administer infusions at least 3 days apart. Assess response 28 ± 2 days after the first dose and administer further treatment as appropriate as described in Table 1 based on Day 28 response. Table 1: Recommended Treatment based on Day 28 Response Response Recommendation Complete Response No further treatment with RYONCIL Partial or Mixed Response Partial response defined as organ improvement of at least one stage without worsening in any other organ, whereas mixed response was defined as improvement of at least one evaluable organ with worsening in another organ as per International Blood and Marrow Transplantation Registry Severity Index Criteria grading system. Repeat administration of RYONCIL once a week for additional 4 weeks (4 infusions total) No Response Consider alternative treatments Recurrence of GvHD after complete response Repeat administration of RYONCIL twice a week for an additional 4 consecutive weeks (8 infusions total) 2.2 Preparation and Administration Instructions Receipt and Storage of RYONCIL RYONCIL is shipped directly to the clinical facility in a liquid nitrogen dry shipper maintained at a temperature of ≤ -135°C. RYONCIL must remain frozen at ≤ -135°C in liquid nitrogen vapor phase until thawed immediately prior to administration [see How Supplied/Storage and Handling (16) ] . Preparation RYONCIL and Plasma-Lyte ® A should be prepared following aseptic technique in a Biological Safety Cabinet (BSC). Spray and wipe down the following materials with 70% alcohol prior to transferring them into the BSC preparation area. All materials should remain in the BSC preparation area unless discarded. Prepare a sterile water bath to a minimum depth of 4 inches and warm to 37°C (± 2°C) at least 30 minutes prior for thawing. Supplies needed for preparation of RYONCIL and Plasma-Lyte ® A RYONCIL vials Plasma-Lyte ® A Infusion bag Interlink blood bag spikes (2) Interlink threaded lock cannula (1 per syringe) 60 mL luer-lock...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most common non-laboratory adverse reactions (incidence ≥20%) are: viral infectious disorders, bacterial infectious disorders, infection – pathogen unspecified, pyrexia, hemorrhage, edema, abdominal pain and hypertension ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Mesoblast at toll-free phone #1-844-889-MESO (6376) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. The safety data described in this section reflect exposure to RYONCIL in 54 patients in Study MSB-GVHD001 for the treatment of SR-aGvHD. Patients received intravenous infusion of RYONCIL at a dosage of 2 x 10 6 MSCs/kg twice a week for four consecutive weeks, for a total of eight infusions. Patients with partial or mixed response at Day 28 received additional infusions of RYONCIL 2 x 10 6 MSCs/kg once a week for an additional four weeks [see Clinical Studies (14) ] . The median number of doses administered were 10 (range 1 to 16), and the treatment was administered over a median of 43 days (range 1 to 104 days). Serious adverse reactions occurred in 35 patients (65%) including pyrexia (n=5;9%), respiratory failure (n=5;9%), pneumatosis intestinalis (n=4;7%) and staphylococcal bacteremia (n=2;<5%). Eight patients had discontinuation of RYONCIL treatment due to the following: acute infusion reactions (n=3), hypotension (n=1), gastroenteritis (n=1), and death (n=3). Table 2 summarizes most common adverse reactions that occurred in ≥10% patients in Study MSB-GVHD001. Table 2: Adverse Reactions** Occurring in ≥10% of Patients in Study MSB-GVHD001 (N=54) a Based on National Cancer Institute Adverse Event Common Toxicity Criteria version 4.03 b No grade 4 or 5 adverse reactions occurred in the study *Is a composite that includes multiple related terms **Includes adverse reactions up to 100 days following RYONCIL treatment Adverse Reactions All Grades a n (%) Grade 3 b n (%) Viral infectious disorders* 30 (56) 8 (15) Bacterial infectious disorders* 24 (44) 10 (19) Infections - pathogen unspecified* 22 (41) 8 (15) Pyrexia 19 (35) 2 (4) Hemorrhage* 15 (28) 4 (7) Edema* 12 (22) 1 (2) Abdominal pain 11 (20) 4 (7) Hypertension 11 (20) 3 (6) Vomiting 10 (19) 3 (6) Arrhythmia* 9 (17) 2 (4) Diarrhea 9 (17) 1 (2) Rash* 9 (17) 0 (0) Arthralgia 8 (15) 0 (0) Fungal infectious disorders* 8 (15) 2 (4) Hypotension 8 (15) 2 (4) Cough 7 (13) 0 (0) Respiratory Failure 6 (11) 6 (11) Table 3 presents the most common grade 3 or 4 laboratory abnormalities that worsened from baseline in ≥10% of patients Table 3: Grade 3 or 4 Laboratory Abnormalities that Worsened from Baseline in ≥ 10% of Patients in Study MSB-GVHD001 (N=54) Laboratory Parameter Grade 3 or higher a % a Based on National Cancer Institute Adverse Event Common Toxicity Criteria version 4.03 Gamma-glutamyl transferase increased 32 Thrombocytopenia 28 Blood bilirubin increased 11

Contraindications

4 CONTRAINDICATIONS Do not use RYONCIL in patients with known hypersensitivity to dimethyl sulfoxide (DMSO) or porcine and bovine proteins. Known hypersensitivity to dimethyl sulfoxide (DMSO) or Porcine and Bovine proteins. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data for RYONCIL use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with RYONCIL to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if RYONCIL has the potential to be transferred to the fetus. Therefore, RYONCIL is not recommended for women who are pregnant. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 10-20%, respectively.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING RYONCIL is supplied as a sterile, cryopreserved cell suspension of ex-vivo culture-expanded allogeneic bone marrow-derived mesenchymal stromal cells (MSC) in vials. RYONCIL is provided as a customized kit to meet dosing requirements for a single dose for each patient [see Dosage and Administration (2.1) ] , with each kit containing: Cartons containing sufficient RYONCIL for one infusion based on the patient weight (see Table 5 ) Sufficient alcohol wipes for preparation of the RYONCIL infusions. Kit sizes and National Drug Codes (NDC) are provided in Table 5. Table 5: RYONCIL Kit Sizes Patient weight (kg) Kit contents (single infusion) Number of kits needed for: 4-vial cartons 1-vial cartons Total cartons Number of alcohol wipes NDC Number Initial course 2 nd course Relapse after CR <12.5 0 1 1 1 73648-111-01 8 4 8 12.5-<25 0 2 2 2 73648-112-02 25-<37.5 0 3 3 3 73648-113-03 37.5-<50 1 0 1 4 73648-114-01 50-<62.5 1 1 2 5 73648-115-02 62.5-<75 1 2 3 6 73648-116-03 75-<87.5 1 3 4 7 73648-117-04 87.5-<100 2 0 2 8 73648-118-02 100-<112.5 2 1 3 9 73648-119-03 112.5-<125 2 2 4 10 73648-120-04 125-<137.5 2 3 5 11 73648-121-05 137.5-<150 3 0 3 12 73648-122-03 RYONCIL is shipped to the clinical facility in a liquid nitrogen dry shipper maintained at a temperature of ≤ -135°C. Storage conditions : RYONCIL must remain frozen at ≤ -135°C in liquid nitrogen vapor phase until thawed immediately prior to administration. Handling : Restrict preparation and administration of RYONCIL to a medical facility in which the medical personnel are trained in aseptic technique. Disposal: Dispose empty or partially used RYONCIL vials according to the institutional guidelines for disposal of biohazard materials. Do not save thawed RYONCIL vials for future use.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.