Written by Emil Luca: Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is caused by a genetic mutation; hence, SMA gene therapy is a lifesaving procedure for the affected infants.
Novartis Gene Therapies introduced ZOLGENSMA, an SMA gene therapy used to treat children less than 2 years old. ZOLGENSMA is given as a one-time infusion into a vein.
ZOLGENSMA is designed to target the genetic root cause of SMA with a one-time-only dose by replacing the function of the missing or nonworking survival motor neuron 1 (SMN1) gene. This gene tells motor neuron cells to produce survival motor neuron (SMN) protein. Motor neuron cells need SMN protein to survive and support muscle functions.
SMA happens when the SMN1 gene is missing or not working properly. The SMN1 gene is the body’s main source of SMN protein, and without it, motor neuron cells may not get the SMN protein they need to survive.
Motor neuron cells control muscle function. When motor neuron cells don’t get enough SMN protein, they stop working. Once they are lost, they cannot be brought back. This means everyday activities like eating, breathing, or sitting up become harder to do, and can be lost permanently.
Without enough SMN protein, motor neuron cells stop working and muscles become weak. With each day that passes without treatment, motor neuron cells become weak and eventually lose all function and die. As a result, things like breathing, eating, swallowing, and speaking become difficult to impossible. Once these cells stop working, the condition is likely to become life threatening.
SMA gene therapy by ZOLGENSMA replaces the function of the missing or nonworking SMN1 gene. ZOLGENSMA is made up of a new, working SMN gene that is placed inside a delivery vehicle, a vector. The vector helps deliver the working SMN gene to motor neuron cells throughout the body.
The vector that delivers the SMN gene is made from a virus called adeno-associated virus 9, or AAV9. This type of virus is not known to make people sick. To make the vector, the DNA of the virus is removed so that the new SMN gene can be put inside. Vectors are used because they can travel throughout the body and deliver the new, working gene to the cells throughout the child’s body. ZOLGENSMA does not change or become a part of the child’s DNA.
With a working SMN gene, motor neurons can keep working as they should. By replacing the function of the SMN1 gene, ZOLGENSMA restores SMN protein production and helps preserve essential muscle function. Motor neuron cells that would have died without treatment can survive and be maintained, stopping the progression of SMA.
ZOLGENSMA stops the progression of SMA and sustains the remaining muscle function needed for children to survive. The earlier treatment with ZOLGENSMA is given, the sooner muscle function may be preserved. ZOLGENSMA is not a cure and cannot reverse the damage already present before treatment.
As to the side-effects, ZOLGENSMA can increase liver enzyme levels and cause acute serious liver injury or acute liver failure. Patients will receive an oral corticosteroid before and after infusion with ZOLGENSMA and will undergo regular blood tests to monitor liver function. Decreased platelet counts could occur following infusion with ZOLGENSMA. Platelet count should be monitored, and attention should be paid to unexpected bleeding or bruising.
One important point to consider is that this SMA gene therapy has a $2.1 million price tag, making it the most expensive medication. With this price, the treatment is inaccessible to some patients. Hopefully, this price may go down in the future.
The writer declares no conflict of interest. Specific information about this product are obtained from the manufacturer’s website. Inquiries are to be addressed to the manufacturer.
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This drug is prepared by the same technology as the Oxford–AstraZeneca COVID-19 vaccine. Yet the vaccine is not so expensive.
Please consider the difference between the demand for the vaccine and for the gene therapy. Treatments for rare diseases pose an economic challenge. The potential market for these drugs is limited. Generating sufficient return on investment from a small patient pool usually requires higher prices.
This price is really very high. It is beyond the reach of most if not all Egyptian families. We have recently had a national campaign in Egypt to collect forty million Egyptian Pounds to treat one child with this disease. This means that for every child to be treated there should be a similar campaign, with no guarantee for success in raising this amount of money in the proper time. Shortly, this price is “impossible” for Egyptian patients.
The high price is really a burden to any patient, in any country. It is the responsibility of insurance and health agencies to help patients with such rare diseases to get the required medication.
The high price is an established feature of orphan drugs, for orphan diseases. Enormous budgets are allocated to discovery of medications for rare diseases. It is well known that most of the work in this direction is destined to fail in producing an approved drug. Putting a limit on the price of a final successful product will halt further research and development of new medications.
An earlier alternative to Zolgensma for treatment of SMA is Spinraza (nusinersen) from Biogen. This is an antisense oligonucleotide, which is administered intrathecally. It aims at producing more working SMN protein from the SMN2 gene by modifying the splicing of its mRNA. This drug costs around $750,000 in the first year, and then $375,000 every year after.
A new oral drug, Evrysdi (risdiplam), also alters SMN2 mRNA splicing. It is taken daily, and its estimated highest annual cost will be $340,000. Roche has been offering the drug globally for free to eligible people through an expanded access program.
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