[Narrator begins speaking]

ZOLGENSMA (onasemnogene abeparvovec-xioi) is a gene therapy for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA).

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ZOLGENSMA has a Boxed Warning for Serious Liver Injury and Acute Liver Failure. Please see additional Important Safety Information at the end of this video. Please see the accompanying Full Prescribing Information.

[DR. TESI ROCHA begins speaking]
We see that the field is evolving, the phenotype is evolving, so because of that, education is key.

[DR. SHIEH begins speaking]
We’re really still working out the details of these emerging phenotypes.

[DR.RAO begins speaking]
A 360-degree approach is absolutely essential. You need to have partners. You need to leverage expertise in different fields.

[DR. SHIEH begins speaking]
It’s important to realize that SMA treatment is individualized. Every patient has different needs. Some patients, for instance, need more pulmonary care. Some patients need more physical therapy. Perhaps some patients also need more orthopedic interventions.

[DR. RAO begins speaking]
When we receive the newborn screen results, there’s a large team that goes into action, and this team is a multidisciplinary team that is involved in taking care of the child. The initial members who receive the diagnosis are the neurologists and the genetic counselors. They have the patient scheduled with the neurologist to go over the diagnosis and the treatment options. But along with that, we make sure that the rest of our team is ready to take care of the patient clinically. And the team does involve members from the physical therapy sciences, occupational therapy, our dietician, our pulmonologist, all of them are aware of a new diagnosis and are ready to see the child if needed.

[DR. TESI ROCHA begins speaking]
We also have pulmonologists, cardiologists, orthopedic doctors, and bone health specialists—endocrinologists—that are part of that team. In certain circumstances, we also have a palliative care team as well. And I like to emphasize that palliative care team shouldn’t be end of life decision making. They’re a great group actually at the time of the diagnosis. And many times, we work with them, particularly when there are ethical questions that come up, and we respect those coming from the families, so that is a team that we also work quite closely with.

[DR. TESI ROCHA begins speaking]
We are now facing a different type of disease than the one that we used to face before the treatment.

[DR. RAO begins speaking]
I am really fortunate to see this in evolution, in my own practice and in my own training. I have seen SMA Type 1 children who were never destined to even live, let alone sit or stand or walk—doing that. So disease-modifying agents have really revolutionized the natural history of progression for SMA. So the question then arises in our mind if they were not supposed to sit, stand, or walk, how are their bodies now going to handle this?

[DR. SHIEH begins speaking]
One of the interesting observations we’ve made is that there are emerging phenotypes in patients with SMA now that they’re undergoing treatment. For instance, we have patients who are now perhaps able to sit but are developing significant scoliosis at a very young age. So the truth is, emerging phenotypes have never been dealt with before. We don’t really have a consensus on how to treat these types of problems.

[DR. TESI ROCHA begins speaking]
But it’s very exciting times for us to be able to have these problems, these new problems regarding SMA care. But we have to keep our eyes wide open, not only for the modifications in the phenotype, but also the potential side effects and long-term effect of the medications. So we always prioritize safety.

[DR. RAO begins speaking]
So seeing these patients over time, following them up, making sure we have a close observation is very, very important to not only study the new natural history of SMA, but to intervene proactively with what we see is coming that we wouldn’t have expected before the disease-modifying treatments were so successful.

[DR. RAO begins speaking]
When I trained in this field, we were handful of people around the country trying to do this. So the whole field has taken hundred steps forward because there are treatment options, not just for families, but for teams and for the future generations who want to train in this and do this, both as their career and as their calling.

[DR. SHIEH begins speaking]
What I want to make sure everyone realizes is that SMA is now a treatable disease. Patients are now, with treatment, living longer lives with a better quality of life as well. And so what we’re going to see is a transformation of patients with SMA.

[DR. TESI ROCHA begins speaking]
These are great, these are fascinating times for someone with SMA, and for all the medical community to have options in terms of treatment. But I think that this is just the beginning. And so, we need time to follow the patients down the road and see what to expect of the long-term effects of these medications.

[DR. RAO begins speaking]
I think one has to always make sure that the families are front and center through all of this. And whatever steps we take for even better treatments in the future should always be centered around the family unit.

[Narrator begins speaking]
Please see additional Important Safety Information at the end of this video.

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Indication and Important Safety Information for ZOLGENSMA (onasemnogene abeparvovec-xioi)

INDICATION

ZOLGENSMA is an adeno-associated virus (AAV) vector-based gene therapy indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.

Limitations of Use
The safety and effectiveness of repeat administration or the use in patients with advanced SMA (eg, complete paralysis of limbs, permanent ventilator dependence) has not been evaluated with ZOLGENSMA.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: Serious Liver Injury and Acute Liver Failure
Cases of acute liver failure with fatal outcomes have been reported. Acute serious liver injury, acute liver failure, and elevated aminotransferases can also occur with ZOLGENSMA. Patients with preexisting liver impairment may be at higher risk. Prior to infusion, assess liver function of all patients by clinical examination and laboratory testing. Administer systemic corticosteroid to all patients before and after ZOLGENSMA infusion. Continue to monitor liver function for at least 3 months after infusion, and at other times as clinically indicated. If acute serious liver injury or acute liver failure is suspected, promptly consult a pediatric gastroenterologist or hepatologist.

WARNINGS AND PRECAUTIONS
Systemic Immune Response
Patients with underlying active infection, either acute or chronic uncontrolled, could be at an increased risk of serious systemic immune response. Administer ZOLGENSMA to patients who are clinically stable in their overall health status (eg, hydration and nutritional status, absence of infection). Postpone ZOLGENSMA in patients with infections until the infection has resolved and the patient is clinically stable.

Thrombocytopenia
Transient decreases in platelet counts, some of which met the criteria for thrombocytopenia, were typically observed within the first 2 weeks after ZOLGENSMA infusion. Monitor platelet counts before ZOLGENSMA infusion and on a regular basis for at least 3 months afterwards.

Thrombotic Microangiopathy
Cases of thrombotic microangiopathy (TMA) were reported to occur generally within the first 2 weeks after ZOLGENSMA infusion. TMA can result in life-threatening or fatal outcomes. Obtain baseline creatinine and complete blood count before ZOLGENSMA infusion. Following infusion, monitor platelet counts closely as well as other signs and symptoms of TMA. Consult a pediatric hematologist and/or pediatric nephrologist immediately to manage as clinically indicated.

Elevated Troponin-I
Increases in cardiac troponin-I levels were observed following ZOLGENSMA infusion. Monitor troponin-I before ZOLGENSMA infusion and on a regular basis for at least 3 months afterwards. Consider consultation with a cardiologist if troponin elevations are accompanied by clinical signs or symptoms.

AAV Vector Integration and Risk of Tumorigenicity
There is a theoretical risk of tumorigenicity due to integration of AAV vector DNA into the genome. Cases of tumor have been reported in patients who received ZOLGENSMA post-approval; a causal relationship has not been established based on tumor analysis. In some cases, limited information was available. Report cases of tumor development in patients who received ZOLGENSMA to Novartis Gene Therapies, Inc. at 1-833-828-3947. 

ADVERSE REACTIONS
The most commonly observed adverse reactions (incidence ≥5%) in clinical studies were elevated aminotransferases and vomiting.

Please see Full Prescribing Information.

Please visit ZOLGENSMA-hcp.com for more information.