Dear Cure SMA Community,
Novartis Gene Therapies is committed to patient safety and the ongoing monitoring of adverse events as it relates to the use of ZOLGENSMA® (onasemnogene abeparvovec-xioi). As with all commercially marketed products, we are continuously monitoring the safety of ZOLGENSMA, and sharing safety data as part of the required pharmacovigilance with health authorities. As a result of reports from post-marketing safety surveillance that have identified thrombotic microangiopathy (TMA) as a safety signal for ZOLGENSMA, we have updated the product prescribing information to add TMA as a Warning & Precaution.
TMA is a rare disease that is characterized by blood vessel damage in association with thrombocytopenia (low platelet counts), hemolytic anemia (low red blood cell counts), and acute kidney injury.1,2 TMA is treatable and can resolve with timely and proper interventions. Early detection is very important. If a child experiences any signs or symptoms of TMA, such as unexpected bruising or bleeding, seizures, or decreased urine output after receiving ZOLGENSMA, it is important to seek medical attention right away.3 TMA has been reported to occur about 1 week after ZOLGENSMA infusion.
ZOLGENSMA is a prescription gene therapy used to treat children less than 2 years old with spinal muscular atrophy (SMA).
*As of January 2021, more than 1,000 children have been treated with ZOLGENSMA worldwide across clinical trials, managed access programs, and in the commercial setting.3As of February 2021, a total of six confirmed TMA cases were reported globally in patients aged 4 months – 4.5 years, with the first case reported in October 2019.3 In all cases, TMA occurred within one to two weeks following dosing, each of the cases responded well to medical intervention, and all patients had subsequent resolution of thrombocytopenia and anemia, as well as recovery of renal function.
Patient safety is our top priority, and given these cases:
- Novartis Gene Therapies reported this information to study investigators last year and, in addition, a series of patient case studies of TMA following treatment with ZOLGENSMA was published in the Journal of Pediatrics in November 2020.
- Novartis Gene Therapies proposed incorporation of TMA into the product prescribing information in all countries where ZOLGENSMA has been approved. Updated product labeling has been approved in the United States (March 16, 2021).
- Healthcare professionals are being informed of the label update via a Dear Health Care Professional Letter. The purpose of the communication is to make doctors aware of the risk of TMA following administration of ZOLGENSMA.
We continue to monitor product safety, including long-term safety follow-up studies in patients treated with ZOLGENSMA. The benefit-risk profile for ZOLGENSMA remains favorable and reported adverse events are monitorable and manageable.
Please continue reading for Important Safety Information, and please see accompanying Full Prescribing Information, including Boxed Warning.
*Please note the Dear Health Care Professional Letter references five reported cases of TMA, as of January 15, 2021. As of February 2021, we are aware of an additional report of TMA for a total of six cases.
US-ZOL-21-0114 03/2021
Questions & Answers
What is thrombotic microangiopathy (TMA)?
TMA is characterized by blood vessel damage resulting in thrombocytopenia, hemolytic anemia and acute kidney injury.1,4 TMA can be genetic or acquired. Acquired TMA can occur in association with a wide range of infections, or can be drug-induced, although it is frequently unclear if this is a direct effect of the pathogen, a side effect of treatment, or a trigger of a latent complement defect.
What is the incidence of TMA and is it more common in patients with SMA?
The incidence of TMA in children with SMA is unknown and it is unclear if there are any predisposing factors and therefore, each situation is unique.1
What is the treatment for TMA?
Each reported case is unique, which means that treatment can vary from symptom management to interventional therapy that could include possible plasmapheresis and/or dialysis.1
What signs or symptoms should patient families/caregivers be looking for?
If a child experiences unexpected bruising or bleeding, seizures, or decreased urine output after receiving ZOLGENSMA, medical attention should be sought. If a child is ill after receiving ZOLGENSMA (fever, vomiting, etc.), it is also important to seek medical attention.2
What additional steps should health care providers take prior to ZOLGENSMA infusion, based on this safety signal and what should they look for following treatment?
A Dear Health Care Professional Communication will be distributed in all relevant regions where ZOLGENSMA is marketed to inform health care providers of the risk of TMA after ZOLGENSMA use.
Does this change patient eligibility for ZOLGENSMA?
No. This does not change patient eligibility for ZOLGENSMA. As with any treatment, physicians should work closely with their patients/patient families to evaluate the benefit-risk profile and determine the best course of action for each individual patient.
TMA is an immune-mediated phenomenon and immune activators may contribute to its development.1 Immune activators (e.g. vaccines, infections) should be avoided or minimized close to ZOLGENSMA dosing.
Please continue reading for Important Safety Information, and please see accompanying Full Prescribing Information, including Boxed Warning.
Indication and Important Safety Information for ZOLGENSMA® (onasemnogene abeparvovec-xioi)
What is ZOLGENSMA?
ZOLGENSMA is a prescription gene therapy used to treat children less than 2 years old with spinal muscular atrophy (SMA). ZOLGENSMA is given as a one-time infusion into a vein. ZOLGENSMA was not evaluated in patients with advanced SMA.
What is the most important information I should know about ZOLGENSMA?
- ZOLGENSMA can cause acute serious liver Liver enzymes could become elevated and may reflect acute serious liver injury in children who receive ZOLGENSMA.
- Patients will receive an oral corticosteroid before and after infusion with ZOLGENSMA and will undergo regular blood tests to monitor liver
- Contact the patient’s doctor immediately if the patient’s skin and/or whites of the eyes appear yellowish, or if the patient misses a dose of the corticosteroid or vomits it up.
What should I watch for before and after infusion with ZOLGENSMA?
- Viral respiratory infections before or after ZOLGENSMA infusion can lead to more serious complications. Contact the patient’s doctor immediately if you see signs of a possible viral respiratory infection such as coughing, wheezing, sneezing, runny nose, sore throat, or
- Decreased platelet counts could occur following infusion with ZOLGENSMA. Seek immediate medical attention if the patient experiences unexpected bleeding or
- Thrombotic microangiopathy (TMA) has been reported to occur approximately one week after ZOLGENSMA infusion. Caregivers should seek immediate medical attention if the patient experiences any signs or symptoms of TMA, such as unexpected bruising or bleeding, seizures, or decreased urine output.
What do I need to know about vaccinations and ZOLGENSMA?
- Talk with the patient’s doctor to decide if adjustments to the vaccination schedule are needed to accommodate treatment with a corticosteroid.
- Protection against respiratory syncytial virus (RSV) is recommended.
Do I need to take precautions with the patient’s bodily waste?
Temporarily, small amounts of ZOLGENSMA may be found in the patient’s stool. Use good hand hygiene when coming into direct contact with bodily waste for 1 month after infusion with ZOLGENSMA. Disposable diapers should be sealed in disposable trash bags and thrown out with regular trash.
What are the possible or likely side effects of ZOLGENSMA?
The most common side effects that occurred in patients treated with ZOLGENSMA were elevated liver enzymes and vomiting.
The safety information provided here is not comprehensive. Talk to the patient’s doctor about any side effects that bother the patient or that don’t go away.
You are encouraged to report suspected side effects by contacting the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch, or Novartis Gene Therapies at 833-828-3947.
Please see the Full Prescribing Information.
Consumer ISI for ZOLGENSMA Q&A Format US-ZOL-20-0105 v2
If you have any questions regarding the use of ZOLGENSMA we encourage you to speak with your health care provider. We are committed to keeping the SMA community informed and value your partnership.
References:
- Chand DH, Zaidman C, Arya K, et al. Thrombotic microangiopathy following onasemnogene abeparvovec for spinal muscular atrophy: a case series [epub ahead of print]. J Pediatr. 2020 Nov 28:S0022-3476(20)31466-9.
- ZOLGENSMA Prescribing Information. Bannockburn, IL: AveXis, Inc; 2021.
- Data on File. Novartis Gene Therapies, Inc. 2021.
- Joly BS, Zheng XL, Veyradier A. Understanding thrombotic microangiopathies in children. Intensive Care Med. 2018;44:1536–1538.
US-ZOL-21-0114 03/2021