Doctors essential in driving access for rare disease treatment
In any disease, the doctor plays a crucial role in first, identifying or diagnosing the disease, then treating or managing it.
Sometimes, they also have to be advocates for their patients.
This is especially so in rare diseases where access to treatments may be limited, due to either the non-availability of the drug in the country, or cost.
In such cases, doctors play not only a critical part in planning and implementing a management plan for the patient, but also a pivotal role in obtaining the necessary medications.
Take for example, the rare genetic disease spinal muscular atrophy (SMA).
Treatments for this progressive neuromuscular condition only became available over the last decade or so (including through participation in clinical trials), with the first one being approved by the US Food and Drug Administration (FDA) in December 2016.
There are currently three approved treatments for SMA: nusinersen, risdiplam and onasemnogene abeparvovec-xioi.
The first two are registered and approved for sale in Malaysia.
However, as Hospital Tunku Azizah (HTA), Kuala Lumpur, consultant paediatric neurologist Dr Poorani Anandakrishnan shares, neither of them are listed in the Health Ministry’s Medicines Formulary, also known informally as the Blue Book.
This means that they are not available for regular prescription in Health Ministry hospitals, nor is their cost covered under the hospital’s budget if permission is obtained to prescribe them.
While the past few years has seen a special allocation for rare diseases included in the national budget, Dr Poorani says that her department has not received any of those monies.
And Universiti Malaya Medical Centre (UMMC) consultant clinical geneticist Professor Dr Thong Meow Keong says that although the rare disease allocation is meant for all, it only goes to Health Ministry hospitals, leaving out those under the Higher Education Ministry and the Defence Ministry, which are also part of the public healthcare system.
As these therapies are expensive – their prices range from around US$340,000 (RM1.5mil) a year for life to about US$2.1 million (RM9.29 million) for a one-time treatment – this makes them out of reach for the vast majority of Malaysian SMA patients.
ALSO READ: Treatments for SMA are available, but unaffordable for most Malaysians
My doctor, the researcher
Fortunately, there are other ways for doctors to help their patients get these treatments, albeit in limited numbers.
As research involving these drugs is still ongoing, it is possible for SMA patients to receive these treatments for free while participating in the relevant clinical trials.
Prof Thong is the lead investigator for the phase 3 clinical trial testing the effectiveness, safety and tolerability of an intrathecal injection of the gene therapy onasemnogene abeparvovec-xioi being conducted at UMMC in Kuala Lumpur.
This one-shot treatment is currently approved by the US FDA for SMA patients less than two years old, to be administered via an intravenous (IV) infusion.
An intrathecal injection is done via a lumbar puncture straight into the spinal cord fluid.
The international, multi-centre clinical trial involves SMA type 2 patients aged two to 18 years old, who have not previously received any drugs for the condition.
Only patients cared for by the doctors involved in the trial, who meet the strict criteria listed, will have an opportunity to participate in it.
While there are a number of factors that go into being chosen as the site of a clinical trial, especially an international one, one of the main reasons is the expertise and research capabilities of its doctors, as well as their willingness to run such trials.
Such access to free treatment is why Dr Poorani is spreading the word for doctors in hospitals that do not have the experience or multidisciplinary teams to manage SMA to refer such patients to HTA.
Aside from providing the patient with the best care, she says: “It is also necessary so that if we have clinical trials for new drugs or any opportunity to try any compassionate access programmes, then we have a ready list where we can pick the patients for all these treatment access programmes.”
She adds: “We want to come up with a patient registry so that it is easier to identify these patients because some of them stay very far away.”
There is no national registry for rare disease patients in Malaysia, although doctors involved in managing these diseases have been calling for one to be set up for years.
ALSO READ: Rare disease advocates call for registry
Linking pharma and patients
Dr Poorani runs the SMA treatment clinic in HTA, which began in 2021.
“Since 2020, we’ve had an allocation from (Swiss healthcare company) Roche for risdiplam to give to 11 patients in Malaysia under their compassionate access programme.
“Then their drug got registered in 2022, so after that, there were no more samples,” she says.
Four of the patients in this programme go to HTA, while the others are managed by a handful of other tertiary hospitals around the country.
While the programme has stopped taking in new patients after the registration of the drug in Malaysia, the 11 who are currently in it are still being provided the treatment for free.
Risdiplam is an oral medication that needs to be taken for the rest of the patient’s life and is approved for SMA patients from birth to 60 years of age.
Prof Thong shares that UMMC was one of the first hospitals in Malaysia to get involved in SMA treatment via a similar programme.
“Onasemnogene abeparvovec-xioi, the gene therapy, was the first one we used in January 2020, and we have treated six patients so far with the IV form,” he says.
These six patients, he shares, received their medications for free via the drug’s global Managed Access Programme.
The programme – run by Swiss-American pharmaceutical corporation Novartis, which produces the drug – allocates up to 100 doses of the medicine every year for qualified patients around the world.
Patient names are submitted by their doctors and are picked at random to receive the drug.
“We were very lucky, because when we first found out about it, we quickly put in quite a number of names, and our first six patients were all selected in the draw,” he says.
According to Dr Poorani, two HTA patients were also fortunate enough to have their names drawn to receive the gene therapy.
All but one of these eight SMA type 1 patients are currently alive, when otherwise, their life expectancy would only be up to two years of age.
ALSO READ: Rare disease drugs can be costly; here are ways to ease the financial burden
Beyond treatment
However, both Prof Thong and Dr Poorani stress that receiving a treatment is not the be-all and end-all of an SMA patient’s journey.
“Treatment is not just about the pharmacological drugs, but sometimes, parents are so taken by pharmacological drugs that the moment you say there is no drug, they will quote the doctor as saying there is no treatment.
“That’s not true; we always advocate a holistic approach to treatment – it’s not just about the pharmacologic agent, it’s also about the non-pharmacological management,” says Prof Thong.
He adds that before the current SMA treatments became available, he’d advise the parents of his patients to keep their child as healthy as possible so that when the drugs arrived in Malaysia, their child could benefit from them.
The current treatments for SMA are not a cure for the condition.
More importantly, they will not enable the patient to recover whatever motor function they may have lost before they received the drug.
For example, if the patient was already unable to walk before receiving the treatment, they would still be unable to walk after taking the drug.
The drug will instead halt their deterioration at the level of their current motor function, which can save and prolong their life.
Says Dr Poorani: “People think, ‘As soon as I get the medicine, I’m ok’. But you still have a long way to go, because this disease, you must treat before there are signs of weakness, then only will you see an almost normal trajectory of development.”
She adds: “Multidisciplinary care is very important.
“You have this small bit which is just the treatment, but the whole patient does not just depend on this treatment – other aspects of care are also needed to look after this child.”
For example, an SMA patient may require:
- A geneticist for diagnosis and counselling.
- A neurologist for neuromuscular issues.
- A respiratory physician to help with weak lungs.
- A physiotherapist, an occupational therapist and a paediatric rehabilitation specialist to help with weak muscles and contractures, and activities of daily living.
- A speech therapist for issues with speaking due to weak muscles.
- A dietitian or nutritionist to help with proper nutrition as they have problems chewing and swallowing.
- An orthopaedic surgeon for scoliosis – an inevitable side effect of the disease.
- A palliative care specialist to minimise pain and enhance quality of life.
ALSO READ: Treatment is not a cure for patients with SMA
And sometimes, parents also need to be counselled on when to let go, especially if their child is not fortunate enough to be able to access the drugs due to cost or lack of time, says Dr Poorani.
“All these years I’ve been treating children, for so many of my children, I’ve had to counsel parents to let go because their child just cannot breathe on their own,” she says emotionally.
“There’s this desperation between the parents, and there’s a desperate doctor who doesn’t know what to do, because I have nothing on my hands, I’ve no treatments.”
This is the fourth and final article of a short series written as part of the US National Press Foundation’s 2022 Covering Rare Diseases: Journalism Fellowship & Global Reporting Grant.
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