Professor Michael Barry:

I thank the committee for inviting us. I will go through the opening statement as follows. At the start of our submission, we highlighted the fact that the term "orphan drug" refers to medicines that are used to treat conditions that affect less than one in 2,000 citizens. While individual orphan conditions may be rare, collectively they are not. The National Rare Disease Strategy 2025-2030 publication highlights that an estimated 300,000 people in Ireland are living with a rare disease. Orphan drugs account for approximately 22% of rapid reviews and 30% of full health technology assessments, and approximately 27% of all medicines reimbursed over the past five years.

To give the committee a flavour of what is happening right now, I will present some statistics for the first nine months, January to September, inclusive, of 2025. Some 36 drugs for 38 therapeutic indications have been considered for reimbursement by the HSE drugs group. Our reports go to the HSE corporate pharmaceutical unit, which then goes to the drugs group. The drugs group makes recommendation for reimbursement for the cost of medicines. The HSE leadership decides whether the cost of a drug will be reimbursed or not. I should say that is not something we decide but we feed into the process. Reimbursement was recommended for 29 of the therapeutic indications reviewed, which equates to 76, and rejected for six, or 15.8%. Orphan drugs accounted for 17 of the 38 indications, or nearly 45%, reviewed by the HSE drugs group and 12 of the 17 orphan drugs were recommended for reimbursement.

Table 1 presents the orphan drugs that have been looked at this year up to 30 September. It starts with artesunate, tafasitamab, iptacopan down to talquetamab, along with the indications. There is a wide variety of indications but many are cancer. Many orphan drugs are for the treatment of cancer as well. Ten of these are cancer drugs. There is an overlap. The reimbursement recommendation is also shown. Just two of the drugs were not recommended for reimbursement, vosoritide for achondroplasia and carfilzomib for multiple myeloma. All of the others were approved for reimbursement. Three are awaiting a decision. This process is ongoing. There may be further price offers and the HSE would consider same.

It can be seen that the majority, 70.6%, of orphan drugs considered were recommended for reimbursement despite the fact that just one of the drugs, imlifidase, in the area of renal transplantation, satisfied the cost-effectiveness threshold for this country, which is €45,000 per quality-adjusted life year. Not all drugs will be subject to a full health technology assessment. Some get through at the rapid review phase. For those that were, ten had an incremental cost effectiveness greater than €100,000 per quality-adjusted life year and four exceeded €200,000 per quality-adjusted life year. Essentially, they were not cost effective. The failure to prove cost effective is likely to be related to the fact that only three of the 17 orphan drugs improved overall survival rates and just two were shown to significantly improve quality of life. For seven of the 17 drugs reviewed, the clinical evidence was based on single-arm clinical trials, meaning there is no comparator. It is very hard to define the relative effectiveness of a drug if there is no comparator in the clinical trial. We see this not just in orphan drugs but also in cancer drugs.

The NCPE assessment process and subsequent price negotiations facilitated the reimbursement of drugs initially deemed not to be cost effective. Just because a drug is not cost effective does not mean it will not be reimbursed. The health technology assessment indicates to the HSE at what price the drug might present value for money and the HSE negotiates the price. Orphan drugs are very expensive. For example, iptacopan for paroxysmal nocturnal haemoglobinuria costs over €400,000 per patient per year at the list price including VAT. Carfilzomib plus daratumumab plus dexamethasone for multiple myeloma costs over €424,000 per treatment course and ciltacabtagene for the treatment of multiple myeloma costs €478,800 per treatment. That is a CAR T-cell therapy. A number of the drugs on the list are CAR T-cell therapies, which are an exciting new innovation but they come at a cost. I also mention in the table the percentage of these drugs that cost over €100,000, €200,000, etc. They are expensive drugs. The five-year gross budget impact for the 17 orphan drugs considered so far in 2025 amounts to €381 million. They are high-cost drugs with a very high budget impact. The HTA process and subsequent negotiations have to date reduced that figure by €142 million, which is now available for something else in the health service. That is the key.