The most expensive treatment in the world
Middle East Health speaks to Dr. Vivek Mundada, Paediatric Neurologist at the Medcare Women & Children Hospital in Dubai, about a revolutionary – and very expensive – gene therapy for Spinal Muscular Atrophy that has been offered for free to two of the hospital’s patients.
Middle East Health: Two patients from Medcare Women & Children Hospital, Dubai, have been selected for a revolutionary – and very expensive – gene therapy procedure for Spinal Muscular Atrophy. They have been offered the therapy for free. Can you explain what Spinal Muscular Atrophy is and how the gene therapy works?
Dr. Vivek Mundada: Spinal Muscular Atrophy is a genetic condition in which a gene called SMN1 is deleted or mutated in the affected individual. It gets worse over time. Most of the nerve cells that control muscles are located in the spinal cord (hence “Spinal”). SMA is muscular because its primary effect is on muscles, which don’t receive signals from these nerve cells. Atrophy is the medical term for getting smaller, which is what generally happens to muscles when they’re not stimulated by nerve cells. SMA involves the loss of nerve cells called motor neurons in the spinal cord and is classified as a motor neuron disease.
SMA is caused by a fault in a gene called Survival Motor Neuron 1 (SMN1). This gene carries the information required for the production of an important protein called SMN. This protein, as its name implies, seems to be necessary for normal motor neuron function. When there is not enough SMN protein, the nerve cells that help control the muscles for moving and breathing become damaged.
There are four main types of SMA:
type 1 – develops in babies less than 6 months old and is the most severe type
type 2 – appears in babies who are 7-18 months old and is less severe than type 1
type 3 – develops after 18 months of age and is the least severe type affecting children
type 4 – affects adults and usually only causes mild problems
Infants with type 1 rarely survive beyond two years of life. Most children with type 2 survive into adulthood, but their life expectancy is still shortened. Types 3 and 4 do not usually affect life expectancy.
We, humans, carry two copies of all the genes: one inherited from the mother and another from the father. When both the copies of SMN1 gene are absent, that individual suffers from SMA. This is called the ‘autosomal recessive’ pattern of inheritance. Usually, both the parents of the affected person have only one copy of SMN1 (and are called ‘carriers’). Such parents have a 25% chance of having a baby affected with SMA. As we now have a treatment, newborn screening (NBS) for SMA in some countries has helped identify babies with this condition early and they can be treated early. It is known that early diagnosis and early treatment improves the prognosis of babies with SMA. Detection of this condition in the foetus is possible during early pregnancy through genetic investigation.
Gene replacement therapy (“onasemnogene abeparvovec-xioi”) essentially means replacing a fully functional copy of the missing SMN1 gene which is the root cause of the SMA disease. The SMN1 gene is inserted into a non-infection causing virus vector called adeno-associated virus (AAV) and this viral vector with the replacement gene is intravenously injected as a single dose into the patient’s blood. The gene then enters targeted body cells and starts producing the missing SMN protein.
Children with SMA1 who usually never achieve the developmental milestone of sitting and have received this gene replacement therapy have learned to sit and have survived with good quality of life. Some have even achieved the milestone of walking. This therapy changes the natural course of the disease as their muscle power increases significantly and hence is the life-saving drug for this condition
Both the children receiving gene therapy under myself have SMA type 1 and were due to receive the treatment on 10 November 2020. These will be the first two children with SMA1 receiving gene therapy in Middle East.
MEH: Can you explain the procedure for the application of the gene therapy?
VM: Both the infants had pre-therapy clinical assessments and necessary blood tests required for the therapy. The drug will be specifically made for these children according to their weight. We have obtained the necessary approvals for the import of the drug from the U.S. and the local import permit from the local authorities is applied.
We will be admitting the children to the intensive care unit. All the nursing staff, pharmacists, and medical staff who will be involved in the care of these children have received two days of training including storage, handling, and preparing the drug for infusion in the hospital setting.
The children will be monitored for at least 24 hours after the infusion. After the discharge, periodic assessments will be done in the outpatient by myself and the paediatric physiotherapist to monitor their progress and other parameters like any side effects of the drug.
Parents have been educated on SMA including various monitoring required for the children. Apart from myself, they have been seen by paediatric respiratory and gastrointestinal specialists. They are also receiving regular physiotherapy. Parents are receiving regular updates on the progress of this therapy.
MEH: For how long has this therapy been used in clinical practice?
VM: This gene therapy (Onasemnogene abeparvovec ) was approved for children in less than two years ago following successful clinical trials. Onasemnogene abeparvovec was approved for medical use in the United States in 2019, and in Japan and the European Union in 2020. In August 2020, onasemnogene abeparvovec was granted regulatory approval in Brazil.
MEH: Where else has this therapy been used and what are the results?
VM: It has been and is still being tested in several different clinical trials (e.g. START, STR1VE EU, STR1VE, STRONG and SPR1NT), which have enrolled a variety of patients with SMA Types (1-2). The gene therapy has been consistently shown to be safe and well tolerated by those treated with the drug.
In the START trial, patients treated with gene therapy have achieved a range of motor milestones never seen in the natural history of the disease without treatment, including sitting, talking and some patients walking, with no reduction of the effect nearly four years after treatment. In the Phase 3 STR1VE trial, this treatment has been confirmed to result in prolonged event-free survival, improvements in muscle function, and achievement of key milestones.
MEH: How much is the procedure and why is it so expensive?
VM: The drug [Zolgensma developed by Novartis] carries a list price of US$2.125 million per treatment, making it the “most expensive” medication in the world as of 2019. Like most breakthrough drugs, Zolgensma’s price reflects the high cost of its development and the value it delivers.
Zolgensma’s price reflects the value it delivers. The only other treatment for SMA, a drug called Spinraza, was approved in 2016. Spinraza treatments cost $625,000 to $750,000 in the first year, and then around $375,000 every year after, likely for the rest of a patient’s life. The single dose of Zolgensma can end up costing half as much as this chronic course of SMA therapy.
According to a 2016 study published in the Journal of Health Economics, it takes, on average, $2.6 billion and over a decade to create a single new drug. And a great deal of drug research ends in failure; just 14% of drugs in clinical trials ultimately receive FDA approval, according to a Massachusetts Institute of Technology (MIT) study.
In Japan, the drug was made available through the public healthcare system on May 20, 2020, making it the most expensive drug covered by the Japanese public healthcare system.
MEH: The therapy is being offered by Novartis. Why are they offering the procedure for free to select patients?
VM: The global Managed Access Program (MAP) for Spinal Muscular Atrophy (SMA) gene therapy (onasemnogene abeparvovec) is available in the countries where this life-saving therapy is not approved by the respective local health authorities. It was announced in December 2019 and the company decided to offer up to 100 free doses in 2020. Their bioethics committee explored various options to make the gene therapy available through a global MAP.
Children under two years with a confirmed diagnosis of SMA are eligible provided they medically meet the inclusion criteria. There is a blinded and random allocation of a few doses each month for all the children enrolled in this program globally and if selected, they can avail the single-dose gene therapy for free.
MEH: What criteria did you use to select the two patients?
VM: As per the inclusion criteria for MAP program,
– Patients under the age of two with genetically confirmed mutations in the SMN1 gene; regardless of type of the disease or symptom onset.
– Geographically, the patient must be a citizen or legal resident of, and eligible for healthcare in, a country where AVXS-101 (Zolgensma) is not approved by local health authorities.
Both these patients were eligible and hence were enrolled in this program.
MEH: Is it likely the procedure will be offered for free to other patients in the UAE or the Middle East region? Is the therapy available to other patients in the Middle East who can afford to pay for it? Where is it available?
VM: The drug can only be available free if the patient is selected under the MAP program. Currently it is not available in the UAE market unlike in US, Japan and Europe.
More information
- For any clinical information, Dr Mundada can be contacted on: vivek.mundada@medcarehospital.com .
- Alternatively, email: reem@genpharmservices.com
- More information on the MAP program can be obtained by emailing: SAbiNakhoul405@avexis.com
