Section 4.4: Update ‘Elevated Troponin-1’ to change in post infusion monitoring requirements .

Section 4.4: Added ‘Infusion-related reactions and anaphylactic reactions’ section that includes information about the occurrence of IRRs, including anaphylactic reactions.

Section 4.8: ‘Infusion-related reactions’ added as a new ADR with ‘uncommon’ frequency and ‘Anaphylactic reactions’ added as a new ADR with ‘rare’ frequency

Section 4.4: Updated to include a cross reference to Section 5.2

Section 5.1: Updated to include efficacy data from the SMART study (COAV101A12306)

Section 5.2: Updates to include more information about vector shedding

• Update of SmPC section 4.4 and 4.8 to inform about an increased risk of AST and/or ALT elevation and thrombocytopenia observed in study in children weighing ≥ 8,5 kg to ≤ 21 kg (aged approximately 1.5 to 9 years) compared with studies in children < 8.5 kg. 
• Update of SmPC section 4.4 and 4.8 to reflect the fact that thrombocytopenia may occur within 3 weeks of administration.
• Update SmPC section 4.8 to update the frequency of TMA and acute hepatic failure to “uncommon”.   

Update section on regular blood tests to state that 'most of the reported cases of a low blood-platelet count occurred within the first two three weeks after the child was given Zolgensma'.

Change frequency of following side effects from 'unknown' to 'uncommon':

• vomiting, jaundice (yellowing of the skin or of the whites of the eyes) or reduced alertness - these may be signs of injury to the liver (including liver failure).
• bruising easily, seizures (fits), decrease in urine output – these may be signs of thrombotic microangiopathy.

Shelf life increased from 18 months to 2 years

Section 4.4 updated to include a theoretical risk of tumourigenicity due to integration of AAV vector DNA into the genome.

Risk of tumours associated with potential insertion into the DNA

First version of the HCP guide

Approval of new version of this material

Shelf life changed from 2 years to 18 months

Information added to 'the 'Liver problems', 'Infection' and 'Abnormal clotting of blood in small blood vessels (thrombotic microangiopathy' sections of the "Warning and Precautions".

Liver failure added as a possible side effect

Section 4.2:

• Pre-treatment laboratory testing updated to include albumin, prothrombin time, partial thromboplastin time (PTT) and international normalised ratio (INR) in the liver function tests
• Include recommendation that patients are clinically stable in their overall health status prior to infusion
• Liver function should be monitored before treatment and regularly for at least 3 months after infusion. Promptly assess patients with worsening liver function tests and/or signs or symptoms of acute illness.
• Patients with positive serology for hepatitis B or hepatitis C have not been studied in clinical studies with onasemnogene abeparvovec.

Section 4.4

Following information added to ‘Hepatotoxicity’:

• Fatal cases of acute liver failure have been reported in patients treated with onasemnogene abeparvovec.
• Promptly assess patients with worsening liver function tests and/or signs or symptoms of acute illness.
• If patients do not respond adequately to corticosteroids, consult a pediatric gastroenterologist or hepatologist and consider adjustment of the corticosteroid regimen.
• AST/ALT/total bilirubin should be assessed weekly for the first month after onasemnogene abeparvovec infusion and during the entire corticosteroid taper period
• Corticosteroids should not be tapered until liver function tests become unremarkable (normal clinical examination, total bilirubin, and ALT and AST levels below 2 × ULN).

Following information added to ‘Thrombotic microangiopathy’ (TMA)

• Cases generally occurred within the first two weeks after onasemnogene abeparvovec infusion. TMA is an acute and life-threatening condition, which is characterised by thrombocytopenia and microangiopathic haemolytic anaemia. Fatal outcomes have been reported.
• In case of thrombocytopenia, further evaluation including diagnostic testing for haemolytic anaemia and renal dysfunction should be undertaken promptly.

Following information added to ‘Systemic immune response’ (‘Immunomodulatory regimen’ renamed)

• Due to the increased risk of serious systemic immune response, it is recommended that patients are clinically stable in their overall health status (e.g. hydration and nutritional status, absence of infection) prior to onasemnogene abeparvovec infusion
• Patients with infection were excluded from participation in clinical trials with onasemnogene abeparvovec.
• Increased vigilance in the prevention, monitoring, and management of infection is recommended before and after onasemnogene abeparvovec infusion.

Section 4.8:

• Fatal cases of liver failure added to table of adverse reactions
• Post-marketing cases with transient decrease in platelet count to levels <25 x 10⁹/L within two weeks of administration have been reported (see section 4.4).

First upload to medicines.ie

Shelf life increase from 1 to 2 years

Further information regarding low blood-platelet counts (thrombocytopenia): "Most of the reported cases of a low blood-platelet count occurred within the first two weeks after the child was given Zolgensma".

Change in Marketing Authorisation Holder to Novartis Europharm

SmPC Section 4.4 and 4.8 updated with additonal information regarding thrombocytopenia

SmPC Section 7 updated with Novartis Europharm as new Marketing Authorisation Holder

Sentence regarding conditional authorization is removed

Updates to 4.8, 5.1 and 5.3 as part of renewal procedure

Changes due to approval of renewal

PIL for new product

SPC for new product