Zolgensma: the most expensive medicine in the world cures AME?

There are many drugs considered “high cost”, that is, that have an exacerbated price and that are usually indicated to treat rare diseases or very specific conditions and syndromes.

The Zolgensma is one such medication, understand what it is for and see more information:


What is Zolgensma?

Zolgensma is well known for being the most expensive medicine in the world , costing more than R $ 10 million per dose. Its use was approved in 2019 in the United States and in 2020 in Brazil, indicated for treating type 1 cases of spinal muscular atrophy ( EBF ), and it can be administered to children up to 2 years old.

This condition generates impairment of the motor system, leading to loss of movement, the need to use respirators due to the atrophy of the respiratory muscles, among other impairments that involve the musculature.

AME is caused by the failure or absence of a gene (SMN1). For this reason, it is considered a genetic condition, more specifically of the rare type (1 case for every 10,000 births).

Regarding the action of the drug Zolgensma, this is made possible through a copy of the SMN1 gene, which is present in its active substance – onasemnogene abeparvovec.

Among the benefits demonstrated by the drug in the studies, it was found that it reduces the need for artificial ventilation in babies with EB. And it also made it possible for these babies to be able to sit unsupported for at least 30 seconds.

These data are very relevant, considering that they are considered basically impossible to be performed by children with untreated type 1 EBF.

It is also worth noting that the application of this medication occurs in a single dose , which is administered through an intravenous infusion in (a) the patient. In the sequence, you can understand more about Zolgensma, its use and possible side effects:

What is the medicine Zolgensma for?

Zolgensma is a biological medication, considered as a gene therapy for the treatment of AME (spinal muscular atrophy). This is a rare genetic disease that affects 1 in 10,000 babies. It is a serious condition that leads to the death of specific cells in the central nervous system (CNS), the “motor neurons”.

With this, muscle degeneration occurs , since the muscles stop receiving information from these neurons. Thus, there is a loss of muscle tone (characterizing hypotonicity) and, then, the musculature becomes weak and this leads to atrophy.

This condition can be classified into 4 types, which classification is made (among other specifications) based on the appearance of symptoms:

Onset of symptomsAME type
0-6 months1
6-18 monthstwo
> 18 months3
From 21 years old4

In this case, the drug Zolgensma is indicated for use in patients up to 2 years old . That is, it can be administered in cases of type 1, 2 and 3 of EBF.

It is worth mentioning that, among all, type 1 is the most common (between 50% and 70% of cases) and type 4 the most rare (5% of cases).

Does Zolgensma cure AME?

No . The active substance in Zolgensma has a copy of the SMN1 gene, which, when damaged or absent, is responsible for causing EBF. Thus, the action of the medicine aims to reactivate nerve functions , as it allows the body to produce SMN proteins again , which guarantee the health of motor neurons.

Despite this, the medication does not recover the damage caused by the disease and does not stop it from existing. What happens is that it does not allow new neurons to be destroyed.

Therefore, until now, EBF is considered a disease that has no cure.

What causes EBF and what are the symptoms?

Spinal muscular atrophy (AME) is caused by the absence or abnormality of the SMN1 gene, which produces a protein (SMN) essential for the survival of motor neurons.

This condition can manifest itself at different moments in life, the most common being that it occurs in the first months of life, characterizing EBF type 1.

Regarding symptoms, they are directly related to the patient’s age. In general, the sooner they appear (type 1, 2 and 3 cases of the disease), the greater the severity of the impact on motor function. The most common are:

  • Muscle weakness ;
  • Breathing difficulties (may cause weak crying and coughing);
  • Swallowing problems (suck and swallow);
  • Scoliosis (abnormal spinal curvature that occurs due to weakness in the muscles that would normally support the spine).

When this disease manifests itself in adulthood (type 4), it is common for the person to present only a certain muscle weakness that, over time, can cause atrophy.

Unfortunately, the vast majority of cases occur in young children. In these circumstances, degeneration is progressive and can affect muscles responsible for performing essential functions (such as eating and breathing) or even lead to paralysis.

Therefore, EBF requires diagnosis as soon as possible. This is done through genetic analysis.

What is it made of: what is the active principle of Zolgensma?

The medicine Zolgensma has as active ingredient the substance onasemnogene abeparvovec . It is considered a gene therapy, indicated especially to treat spinal muscular atrophy (EBF) in patients up to 2 years old.

Precisely, the package leaflet for this substance indicates that the medication can be administered for the treatment of these patients with:

  • Biallelic mutations in the motor neuron 1 survival gene (SMN1) and clinical diagnosis of type I AME ;
  • Biallelic mutations in the motor neuron 1 survival gene (SMN1) and up to 3 copies of the motor neuron 2 survival gene (SMN2).

These conditions can only be determined from a genetic examination, which is usually requested in cases of suspected syndrome or condition, such as EBF.

How it works: mechanism of action

As mentioned in the previous topic, the active ingredient in Zolgensma is the substance onasemnogene abeparvovec . The action of this compound is possible because it contains a functional copy of the SMN1 gene (gene that triggers AME) in its formula.

Thereafter, when the medication comes in contact with the patient’s organism, it reaches the musculature and supplies the necessary gene to produce the SMN protein .

This protein is responsible for ensuring the survival of motor neurons, those that conduct nerve impulses to the effector organs (perform responses to stimuli).

Basically, then, the Zolgensma mechanism is based on restoring the nervous function of the patient affected by EBF. This, since it provides a copy of the gene that is impaired or absent, which triggers spinal muscular atrophy.

But it is necessary to reinforce that this remedy does not reverse the damage already caused to neurons, it just prevents further damage from being caused and interrupts the degenerative process.

With this, it allows the child’s organism to function the way it should, if it did not have the genetic alteration in the SMN1 gene.

How to use?

Zolgensma is administered by intravenous infusion (medication directly into the vein), in a single dose . This procedure lasts around 1 hour and must be done by a duly trained professional, which can only be performed in a hospital environment .

The drug Zolgensma is administered through a venous infusion, thus, the medicine is dripped directly into the patient’s vein.

The medical team will prepare the medicine, following the procedures indicated on the package insert and also according to the dose required for the patient. This dosage is defined according to the child’s weight – the higher the weight, the higher the dose.

It should be noted that before Zolgensma is administered, a series of tests is required and after the procedure as well. So, it is common for several clinical tests to be carried out, mainly on the liver and blood.

It may also be necessary to use corticosteroids (anti-inflammatory action) after this process, in order to reduce possible side effects of Zolgensma.

What are the side effects of Zolgensma?

Studies on the side effects of Zolgensma show that the most common, reported so far, was the increase in enzymes produced by the liver and the occurrence of nausea and vomiting .

In addition, it can be noted that some patients had other reactions:

  • Blood and lymphatic system disorders – thrombocytopenia ;
  • General disorders and conditions related to administration – pyrexia (fever);
  • Hepatobiliary disorders – hypertransaminasemia ;
  • Others – elevation of transaminases (classified as very common ), elevation of aspartate aminotransferase (AST), elevation of alanine aminotransferase (ALT), elevated troponin I, thrombotic microangiopathy.

It is worth remembering that, as with other medications, although there is a possibility that the patient may have some side effect, it does not mean that everyone will have one (or more) of these effects. There are, for example, those who do not suffer from any adverse reaction.

Especially in the case of Zolgensma, the patient’s monitoring is even greater than in other circumstances, considering the rare factor that is EBF (spinal muscular atrophy).

What is the price and where to buy? Are you in SUS?

Zolgensma is considered the most expensive drug in the world, its price, in dollars, is US $ 2.1 million (about R $ 11.5 million ), which corresponds to the single required dose. This medicine is produced by Novartis and is marketed in the United States.

Recently, in December 2020, the Medicines Market Regulation Chamber (CMED) determined the maximum value for marketing Zolgensma in Brazil to be R $ 2.878 million. Thus, the sale of the drug is already authorized in the country, but the laboratory can still appeal to the decision of the responsible agency.

The drug is not provided by SUS, but many families have filed lawsuits in order for the government to pay for the treatment of EBF.

But it is worth mentioning that another medicine used in the treatment of spinal muscular atrophy is part of the SUS list, Spinraza . This is not a single dose therapy, 6 doses are required in the first year and 3 each year of the patient’s life, costing R $ 145 thousand each.

The perspective is that, although it is a high-cost medication, it is possible to adapt the price of Zolgensma to the reality of the country, so that it can be made available by SUS for the treatment of patients diagnosed with type 1 EBF.