Donislecel

Pancreatic islets regulate blood glucose levels through secretion of multiple hormones in response to increases and decreases in blood glucose. Endocrine cells within pancreatic islets release insulin, glucagon, somatostatin, pancreatic peptide, and ghrelin.

• LANTIDRA is an allogeneic pancreatic islet cellular therapy indicated for the treatment of adults with Type 1 diabetes who are unable to approach target HbA1c because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education. Use LANTIDRA in conjunction with concomitant immunosuppression.ICD-10: E10.9

• Do not administer LANTIDRA to patients who have concomitant diseases or conditions, including pregnancy, that contraindicate the procedure for LANTIDRA infusion or immunosuppression. LANTIDRA is contraindicated in patients for whom immunosuppression is contraindicated.contraindicated

For infusion into the hepatic portal vein only. For infusion into the hepatic portal vein only. Do not irradiate. Do not use leukodepleting filters . Do not use if product time exceeds 48-hours post product release or if temperature is not maintained between 15 and 25° C To be prepared and administered only by medical professionals experienced in islet cell transplantation ( 2.2 ) ( 2.3 ) The recommended minimum dose is 5,000 equivalent islet number (EIN) per kg patient body weight for initial infusion (transplant) and 4,500 EIN/kg for subsequent infusions (same recipient). ( 2.1 ) Administer cells through the hepatic portal vein using a 5 or 6 French angiographic catheter indicated for infusion of LANTIDRA ( 2.3 ). The estimated tissue volume should not exceed 10 cc per transplant infusion. ( 2.1 ) 2.1 Recommended Dose The recommended minimum dose is 5,000 EIN/kg for initial infusion and 4,500 EIN/kg for subsequent infusion in the same recipient. The maximum dose per infusion is dictated by the estimated tissue volume, which should not exceed 10 cc per infusion, and the total EIN present in the infusion bag (up to a maximum of 1 × 10 6 EIN per bag). A second infusion may be performed if the patient does not achieve independence from exogenous insulin within one year of infusion or within one year after losing independence from exogenous insulin after a previous infusion. A third infusion may be performed using the same criteria as for the second infusion. There are no data regarding the effectiveness or safety for patients receiving more than three infusions.

Risks from Concomitant Immunosuppression: Increased risk of severe infections including opportunistic infections, malignancy, and severe anemia. Monitor closely. Administer PCP and CMV prophylaxis. ( 5.1 ) Procedural Complications: Liver laceration and hemorrhage have occurred. Monitor for bleeding, portal hypertension, and portal vein thrombosis during and immediately following infusion. ( 5.2 ) Increased Risk of Graft Rejection : Patients with a positive T- and B-cell crossmatch between recipient serum and donor lymphocytes may be at increased risk for graft rejection. ( 5.3 ) Transmission of Donor-Derived Infections : Monitor for signs of infection following infusion and treat accordingly. ( 5.4 ) Panel Reactive Antibodies (PRA) : Product administration may elevate PRA and negatively impact candidacy for renal transplant. ( 5.5 ) 5.1 Risks from Concomitant Immunosuppression Concomitant use of immunosuppression is required to maintain islet cell viability. The use of immunosuppression in patients receiving LANTIDRA increases the risk of serious and potentially fatal adverse reactions. [Adverse Reactions (6.1)] Patients receiving immunosuppressants are at increased risk of: Bacterial, viral, fungal, and parasitic infections, including opportunistic infections. Lymphomas and other malignancies, particularly of the skin. Severe anemia, sometimes requiring transfusion. Before Treatment Vaccination: To mitigate the risk of infection, patients should receive recommended immunizations prior to treatment.

Ninety percent (90%) of subjects had at least one serious adverse reaction. The major causes were attributed to: Infusion procedure liver laceration/hematoma, hemorrhage, and intra-abdominal bleeding (13%) elevation of portal pressure (7%) Immunosuppression Infection (87%) Malignancy (37%) Ninety percent (90%) of subjects had at least one serious adverse reaction. ( 6.1 ) The major causes are attributed to: Infusion procedure liver laceration/hematoma, hemorrhage, and intra-abdominal bleeding (13%) elevation of portal pressure (7%) Immunosuppression Infection (87%) Malignancy (37%) To report SUSPECTED ADVERSE REACTIONS, contact CellTrans at 1-800-500-1617 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because 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 of LANTIDRA in subjects with type 1 diabetes and hypoglycemic unawareness was demonstrated in two clinical trials (Study 1, Study 2) involving a total of 30 subjects who received between one and three doses of LANTIDRA. Duration between first and second transplant was one month to 2.8 years and between second and third dose from 3 months to 7.8 years (See Figure 1 ). Because of the variable duration of follow-up, number of infusions, and interval between infusions, adverse reactions were reported for the total duration for which each subject was followed.

8.1 Pregnancy Risk Summary Pregnancy risk has not been assessed for LANTIDRA. No animal reproductive and development toxicity studies have been conducted with LANTIDRA. However, there is a risk of fetal malformations associated with certain immunosuppression medications that may be used following LANTIDRA administration. Additionally, the risks to the patient and fetus from the procedure for LANTIDRA infusion in pregnant women has not been assessed. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. 8.2 Lactation Risk Summary The risk of exposing a child to LANTIDRA components during breastfeeding has not been assessed. However, some required concomitant medications, including immunosuppressants, may be excreted in milk at least in trace amounts. Because of this, a decision should be made about whether to discontinue breastfeeding in patients who will receive a LANTIDRA infusion. 8.3 Females and Males of Reproductive Potential Pregnancy Testing Due to the risk of fetal malformations associated with required concomitant medications, including immunosuppressants, females of reproductive potential should have a confirmed negative pregnancy test prior to LANTIDRA infusion.

The 1 most recently updated of 1 ClinicalTrials.gov registrations naming Donislecel as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Islet Transplantation in Type I Diabetic Patients Using the University of Illinois at Chicago (UIC) Protocol
  Approved for marketing · Expanded access · CellTrans Inc.
  NCT03791567updated 2024-10-22

Frequently asked questions

How does Donislecel work?

Pancreatic islets regulate blood glucose levels through secretion of multiple hormones in response to increases and decreases in blood glucose. Endocrine cells within pancreatic islets release insulin, glucagon, somatostatin, pancreatic peptide, and ghrelin.

What is Donislecel used for?

According to FDA labeling, Donislecel carries indications including: LANTIDRA is an allogeneic pancreatic islet cellular therapy indicated for the treatment of adults with Type 1 diabetes who are unable to approach target HbA1c because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education. Use LANTIDRA in conjunction with concomitant immunosuppression.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Donislecel?

Donislecel is classified as Other drugs used in diabetes, Increased Insulin Secretion, Pancreatic Islet Activity Alteration.

What are the brand names for Donislecel?

Donislecel is marketed under brand names including Lantidra.

What are the contraindications for Donislecel?

Donislecel labeling lists contraindications including: Do not administer LANTIDRA to patients who have concomitant diseases or conditions, including pregnancy, that contraindicate the procedure for LANTIDRA infusion or immunosuppression. LANTIDRA is contraindicated in patients for whom immunosuppression is contraindicated.. Always consult the full prescribing information and a clinician.