LENMELDY
Generic: ATIDARSAGENE AUTOTEMCEL
Basic Information
Manufacturer
Orchard Therapeutics (Europe) Ltd
Product Type
CELLULAR THERAPY
Route of Administration
INTRAVENOUS
FDA Set ID
b3e307a7-561b-43b6-a784-9cb1dcfc5196
Indications & Usage
1 INDICATIONS AND USAGE LENMELDY is indicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD).
LENMELDY is an autologous hematopoietic stem cell-based gene therapyindicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD).
LENMELDY is an autologous hematopoietic stem cell-based gene therapyindicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD).
Adverse Reactions
6 ADVERSE REACTIONS The most common non-laboratory adverse reactions (occurring in ≥10% of all children within Year 1 of treatment) were: febrile neutropenia (85%), stomatitis (77%), respiratory tract infections (54%), rash (33%), device related infections (31%), other viral infections (28%), pyrexia (21%), gastroenteritis (21%), and hepatomegaly (18%).
The following clinically significant adverse reactions are described elsewhere in the labeling: Thrombosis and Thrombotic Events [ see Warnings and Precautions (5.1) ] Encephalitis [ see Warnings and Precautions (5.2) ] Serious Infection [ see Warnings and Precautions (5.3) ] Veno-occlusive Disease [ see Warnings and Precautions (5.4) ] Delayed Platelet Engraftment [ see Warnings and Precautions (5.5) ] Neutrophil Engraftment Failure [ see Warnings and Precautions (5.6) ] Insertional Oncogenesis [ see Warnings and Precautions (5.7) ] Hypersensitivity Reactions [ see Warnings and Precautions (5.8) ] The most common non-laboratory adverse reactions (incidence ≥ 10%) were: febrile neutropenia (85%), stomatitis (77%), respiratory tract infections (54%), rash (33%), device related infections (31%), other viral infections (28%), pyrexia (21%), gastroenteritis (21%), and hepatomegaly (18%).
( 6.1 ) The most common laboratory abnormalities were: elevated D-dimer (67%), neutropenia (28%), and elevated liver enzymes (23%).
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Orchard Therapeutics at toll-free phone 1-888-878-0185 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 data reflect experience from 39 children with MLD treated in clinical trials of LENMELDY: PSLI (n=20), PSEJ (n=7), ESEJ (n=10), and 2 children with advanced disease at the time of treatment [ see Clinical Studies (14) ].
The median (min, max) years of follow-up for the safety population was 6.8 (0.6, 12.2).
Table 2 presents the non-laboratory treatment emergent adverse reactions occurring in ≥10% of all children with onset reported on or after the date of conditioning up to 1 year follow-up post-treatment.
Table 2: Summary of Non-Laboratory Treatment Emergent Adverse Reactions Reported in at Least 10% of Patients Within Year 1 Following Treatment with LENMELDY (N = 39) Includes adverse events potentially related to busulfan myeloablative conditioning.
Adverse reaction System Organ Class/Preferred Term Any Grade n (%) patients Grade 3 or higher n (%) patents Blood and lymphatic system disorders -- -- Febrile neutropenia 33 (85) 32 (82) Gastrointestinal disorders -- -- Stomatitis 30 (77) 29 (74) General disorders and administration site conditions -- -- Pyrexia 8 (21) 1 (3) Hepatobiliary disorders -- -- Hepatomegaly 7 (18) 0 Infections and infestations -- -- Respiratory tract infections Includes events with PTs of Bronchitis, Nasopharyngitis, Pharyngitis, Pneumonia, Respiratory tract infection, Rhinitis, Tonsillitis, Upper respiratory fungal infection and Upper respiratory tract infection.
21 (54) 3 (8) Device related infection Includes events of Bacterial sepsis, Catheter site cellulitis, Catheter site infection, Device related infection, Sepsis, and Vascular device infection.
12 (31) 7 (18) Gastroenteritis Includes events with PTs of Enteritis, Gastroenteritis, Gastroenteritis Aeromonas and Gastroenteritis rotavirus.
8 (21) 3 (8) Other viral infections Includes events with PTs of Adenovirus infection, Cytomegalovirus infection, Cytomegalovirus test positive, Cytomegalovirus viremia, Enterovirus infection, Hand-foot-and-mouth disease, Herpes zoster, SARSCov-2-test positive, and Viral infection (excluding PT of Gastroenteritis rotavirus).
11 (28) 2 (5) Skin and subcutaneous tissue disorders -- -- Rash Includes events with PTs of Dermatitis, Dermatitis bullous, Rash, Rash erythematous, Drug eruption and Rash maculopapular.
13 (33) 3 (8) In clinical trials of LENMELDY, 11 children (28%) developed an adverse event of neutropenia following conditioning, 8 of which (21%) reported a Grade 3 event.
Despite best clinical practices including transfusion to prevent severe anemia, three children (8%) developed an adverse event of anemia, 1 of which reported a Grade 3 event.
Nine children (23%) developed elevated liver enzymes, including three children (8%) who developed a Grade 3 event.
Elevated levels of D-dimer (greater than 4.2 nmol/L) have been reported in 26/39 (67%) children during clinical trials of LENMELDY.
Abnormal values up to 109.5 nmol/L were identified at timepoints from Day 21 to Year 7 after LENMELDY infusion, with no pattern identified.
Other clinically important events that occurred in < 10% of the population included the following: One child reported Grade 3 adverse reactions of elevated alanine- and aspartate transaminases which met the definition of Hy’s Law at day 14 after LENMELDY infusion and resolved without treatment by 9 months after initial onset.
Two children reported Grade 3 elevations in liver enzymes, and 1 child reported Grade 1 elevations in liver enzymes.
All events resolved without treatment and are considered related to conditioning.
The following clinically significant adverse reactions are described elsewhere in the labeling: Thrombosis and Thrombotic Events [ see Warnings and Precautions (5.1) ] Encephalitis [ see Warnings and Precautions (5.2) ] Serious Infection [ see Warnings and Precautions (5.3) ] Veno-occlusive Disease [ see Warnings and Precautions (5.4) ] Delayed Platelet Engraftment [ see Warnings and Precautions (5.5) ] Neutrophil Engraftment Failure [ see Warnings and Precautions (5.6) ] Insertional Oncogenesis [ see Warnings and Precautions (5.7) ] Hypersensitivity Reactions [ see Warnings and Precautions (5.8) ] The most common non-laboratory adverse reactions (incidence ≥ 10%) were: febrile neutropenia (85%), stomatitis (77%), respiratory tract infections (54%), rash (33%), device related infections (31%), other viral infections (28%), pyrexia (21%), gastroenteritis (21%), and hepatomegaly (18%).
( 6.1 ) The most common laboratory abnormalities were: elevated D-dimer (67%), neutropenia (28%), and elevated liver enzymes (23%).
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Orchard Therapeutics at toll-free phone 1-888-878-0185 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 data reflect experience from 39 children with MLD treated in clinical trials of LENMELDY: PSLI (n=20), PSEJ (n=7), ESEJ (n=10), and 2 children with advanced disease at the time of treatment [ see Clinical Studies (14) ].
The median (min, max) years of follow-up for the safety population was 6.8 (0.6, 12.2).
Table 2 presents the non-laboratory treatment emergent adverse reactions occurring in ≥10% of all children with onset reported on or after the date of conditioning up to 1 year follow-up post-treatment.
Table 2: Summary of Non-Laboratory Treatment Emergent Adverse Reactions Reported in at Least 10% of Patients Within Year 1 Following Treatment with LENMELDY (N = 39) Includes adverse events potentially related to busulfan myeloablative conditioning.
Adverse reaction System Organ Class/Preferred Term Any Grade n (%) patients Grade 3 or higher n (%) patents Blood and lymphatic system disorders -- -- Febrile neutropenia 33 (85) 32 (82) Gastrointestinal disorders -- -- Stomatitis 30 (77) 29 (74) General disorders and administration site conditions -- -- Pyrexia 8 (21) 1 (3) Hepatobiliary disorders -- -- Hepatomegaly 7 (18) 0 Infections and infestations -- -- Respiratory tract infections Includes events with PTs of Bronchitis, Nasopharyngitis, Pharyngitis, Pneumonia, Respiratory tract infection, Rhinitis, Tonsillitis, Upper respiratory fungal infection and Upper respiratory tract infection.
21 (54) 3 (8) Device related infection Includes events of Bacterial sepsis, Catheter site cellulitis, Catheter site infection, Device related infection, Sepsis, and Vascular device infection.
12 (31) 7 (18) Gastroenteritis Includes events with PTs of Enteritis, Gastroenteritis, Gastroenteritis Aeromonas and Gastroenteritis rotavirus.
8 (21) 3 (8) Other viral infections Includes events with PTs of Adenovirus infection, Cytomegalovirus infection, Cytomegalovirus test positive, Cytomegalovirus viremia, Enterovirus infection, Hand-foot-and-mouth disease, Herpes zoster, SARSCov-2-test positive, and Viral infection (excluding PT of Gastroenteritis rotavirus).
11 (28) 2 (5) Skin and subcutaneous tissue disorders -- -- Rash Includes events with PTs of Dermatitis, Dermatitis bullous, Rash, Rash erythematous, Drug eruption and Rash maculopapular.
13 (33) 3 (8) In clinical trials of LENMELDY, 11 children (28%) developed an adverse event of neutropenia following conditioning, 8 of which (21%) reported a Grade 3 event.
Despite best clinical practices including transfusion to prevent severe anemia, three children (8%) developed an adverse event of anemia, 1 of which reported a Grade 3 event.
Nine children (23%) developed elevated liver enzymes, including three children (8%) who developed a Grade 3 event.
Elevated levels of D-dimer (greater than 4.2 nmol/L) have been reported in 26/39 (67%) children during clinical trials of LENMELDY.
Abnormal values up to 109.5 nmol/L were identified at timepoints from Day 21 to Year 7 after LENMELDY infusion, with no pattern identified.
Other clinically important events that occurred in < 10% of the population included the following: One child reported Grade 3 adverse reactions of elevated alanine- and aspartate transaminases which met the definition of Hy’s Law at day 14 after LENMELDY infusion and resolved without treatment by 9 months after initial onset.
Two children reported Grade 3 elevations in liver enzymes, and 1 child reported Grade 1 elevations in liver enzymes.
All events resolved without treatment and are considered related to conditioning.