The public debate on whether the Hong Kong government should subsidise expensive medications for rare diseases patients continues weeks after Yin-Lan Chi's death in her years-long battle against tuberous sclerosis complex (TSC).

Although there is no cure for TSC, certain studies have shown that the mammalian target of rapamycin (mTOR) inhibitors are effective in managing its symptoms. However, the medication is yet to be listed under the Drug Formulary, making it difficult for Chi to afford the expensive cost. Her death took place two weeks after she pleaded for subsidies during a Legislative Council meeting.

Chi (second from left) and Rebecca Pui-Ling Yuen (first from right), chairwoman of the Tuberous Sclerosis Complex Association, attended the legislative meeting on April 11. (Source: Tuberous Sclerosis Complex Association of Hong Kong's Facebook page)
Chi (second from left) and Rebecca Pui-Ling Yuen (first from right), chairwoman of the Tuberous Sclerosis Complex Association, attended the legislative meeting on April 11. (Source: Tuberous Sclerosis Complex Association of Hong Kong's Facebook page)

What is tuberous sclerosis complex (TSC)? What are the treatment options?

TSC is a genetic disorder characterised by growth of benign tumours in different parts of the body. In most cases, the disease affects the skin, brain, kidney and other organs. Tumour growth in vital organs may lead to serious health issues.

In Chi’s case, the tumours in her stomach have grown to a size that many had mistaken her as a pregnant woman. She also experienced life-threatening rupture of the tumours.

During the meeting, Chi brought up her financial challenges as the tumours have grown on her face. According to Chi, employers had been turning her down because of her physical appearance. In addition, Chi’s 13-year old daughter has inherited the same condition.

Symptoms of TSC among children differ from adults. Most of young patients may suffer from developmental problems or seizure.

"There is a 50 per cent chance of children inheriting TSC if either one or both parents suffer from TSC," said Dr Godfrey Chi-Fung Chan, Head of Department of Paediatrics and Adolescent Medicine at The University of Hong Kong (HKU). "Close to half of TSC patient group suffers from rhabdomyosarcoma, with 80 to 90 per cent of children experiencing seizures, and 90 per cent suffers from skin abnormalities," he added.

Currently, surgeries are the most common options when tumours lead to compression on organs. Unfortunately, surgical removal of tumours does not stop them from growing.

In 2010, pharmaceutical companies discovered two drug options to inhibit tumour growth in TSC patients. At present, there are more than 20 patients in Hong Kong enrolled in the study of said medications. Dr Chan's team has also initiated a three-year study on drug efficacy starting September 2015.

Evidence of mTOR inhibitors in reducing tumour size

The uncontrolled growth of tumours in TSC patients is linked with mTOR. Hence, the discovery of mTOR inhibitors are claimed to be effective for the treatment of TSC.

Everolimus has been approved for subependymal giant cell astrocytomas (SEGAs) and renal angiomyolipomas in TSC patients. Meanwhile, sirolimus has not been approved for use due to its clinical safety profile. SEGAs is the characteristic of brain manifestation of TSC while renal angiomyolipomas is the characteristic of kidney manifestation of TSC.

> Read more: Breakthrough for rare unnamed genetic disease that causes neurological and motor problems

Everolimus sparkled hope when it was found to reduce growth of tumours in TSC patients. Of 111 patients who received everolimus, 57.7 per cent achieved more than 50 per cent reduction in the sum volume of SEGA lesions from the baseline.

On the other hand, of 41 patients, 73.2 per cent achieved reduction of renal angiomyolipomas. In 105 patients with skin lesion, 58.1 per cent responded well towards everolimus. Clinical findings support the hypothesis that everolimus can safely reverse multisystem manifestations of TSC in a significant proportion of patients.

Should taxpayers pay for the subsidies on rare disease medications?

In response to Chi’s request, Director of Cluster Services Dr Wai-Lun Cheung said that the medication Afinitor® (everolimus) has been scheduled to be listed in the Samaritan Fund by July this year. However, its use is confined to only the brain manifestation of TSC. Currently, the medication costs up to HKD$20,000 per month.

As Afinitor® does not promise a curative effect for all TSC patients, the Hospital Authority is currently discussing with experts for the drug’s clinical use other than brain manifestation of TSC.

For Chi, the use of everolimus was a dream that never get to come true. The Hong Kong Alliance for Rare Diseases hoped that Chi’s daughter could benefit from the drug. For the betterment of the minority group suffering from rare diseases, Chi’s death served as a wake-up call to lawmakers. It also raised questions on whether money from taxpayers should be spent on subsidising drugs on these rare diseases.

Chi expressed her wishes during the Panel on Health Services Meetings as she pleaded the Hong Kong government to subsidise expensive medications for rare diseases patients. (From 45:38 to 48:42)

"A human life is priceless and you cannot put a price tag on it," said Democratic Party lawmaker Cheuk-Ting Lam. Lam also accused the government of being inhumane as it denied treatment because of economic concerns, despite having hundreds of billions of fiscal reserves.

While no one would reject the idea of bringing a better future for the minority group that suffers from rare genetic diseases, some also call for a thoughtful discussion to prevent wastage of resources.

> Read more: Orphan drugs - Exactly how much of a financial burden are these?

One example that policy makers should take note of is the NHS Cancer Drugs Fund (CDF) in England. According to a new study published in the journal Annals of Oncology, the fund has cost the taxpayers of the United Kingdom a total of £1.27 billion from 2010 when it started to 2016 when it closed. However, the fund failed to extend the lives of UK cancer patients.

“A ring-fenced drugs fund was created despite a lack of evidence that prioritising drug expenditure would improve outcomes for cancer patients over and above greater investment in the whole cancer management pathway, which includes screening, diagnostics, radiotherapy, surgery and palliative care," said Co-lead author Professor Richard Sullivan, Director of the Institute of Cancer Policy, King’s College London. “Our findings underline the importance of reimbursement decisions for all drugs, procedures and interventions in cancer care being made through appropriate health technology appraisal processes. Only in this way will decisions be made on the best available evidence so as to maximise the value for cancer patients and society as a whole.” MIMS

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Orphan drugs: Are they saving or breaking healthcare?
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Orphan Diseases and Orphan Drugs: What a pharmacist should know