Market Access Orphan Drugs

Interview Transcript

Article | Market Access Orphan Drugs
21st April 2021 Atheneum Team

Expert Profile


Member of the Portuguese National Coordination for Medication and Health Products, Ministry of Health. Associate Professor at the University of Lisbon.


University of Lisbon, Portuguese National Coordination for Medication and Health Products, Ministry of Health


Helder has more than 15 years of senior executive expertise in the fields of pharmacology and regulatory affairs in Portugal with regards to market access and reimbursement of pharmaceuticals. He is a key contributor to the development of health policy and possesses a profound understanding of current policies and regulations affected by changes in the scenario of medical care, insurance and reimbursement facilities.

Section 1: Current Landscape

1.1. How would you describe the current market access landscape for orphan drugs?

First of all, my experience with orphan drugs is from the regulatory point of view and also the decisions on the pricing and reimbursement of these kinds of products. I was for 12 years member of the management board of the National Conference Authority here in Portugal that is responsible for all marketing authorization, but also for prices and reimbursement and all the HTA assessment as well. So, everything is in the same authority, and I was responsible for that for more than 10 years. The other one is that I was the member of the management board of the EMA and also member of the CHMP for one year, but I had the opportunity to see how things work in terms of orphan designation and assessment for marketing authorization of orphan drugs in Portugal.

I think that orphan drug access is not very different compared to other European countries, but in Portugal have a problem when we talk about orphan drugs with regards to the price and the HTA assessment that is more difficult, and that there are a lot of limitations when you want to do a proper HTA assessment. This is a part of the problem on the decisions about pricing and reimbursement of orphan drugs, taking into consideration the N70. This is a problem very specific to orphan drugs. There are limited number of patients and sometimes the characteristics of the diseases. The reasons are there is very weak evidence in order to decide on a reimbursement of these kinds of drugs. The second problem is the price, the thing is that all these new orphan drugs coming to the markets are very expensive.

1.2. What are the biggest challenges around enabling access to orphan drugs?

During the HTA, you have to characterize the added value of these new specificity tools. For orphan drugs, you will have very limited evidence in order to characterize the added value of the product. Frequently you don’t have phase three clinical drugs, and because of the characteristics of the diseases and then met needs in a disease that is very severe and can be even lethal. The second thing is even when you have phase three studies, the number of patients is very limited. So, the robustness of the data is always very limited. This is a problem when you apply the HTA methodologies to this kind of product and this is something that is shared by all the HTA authorities.

We have an additional problem in Portugal that you can decide based on high uncertainty, but the important step forward is to have a registry in order to measure in real world with patients if the value that you gave to the product when you decide to reimburse, are confirmed or not. If not, you have to reassess the value of the drug and propose new conditions for financing. In Portugal, we have in some of the diseases a lack of good registries in other to reassess the drug, and this is a specific problem. It’s not only in Portugal, but we do have this problem of lack of good registries in some of the rare diseases.

We don’t have a national strategy for registries in these kind of diseases with a proper strategy, because we have some positive aspects when we talk about rare diseases. The problem is a large number of diseases, but the good thing is that you have a very limited number of patients in each disease. So, you can register properly all relevant data in all patients if you have a registry strategy, because they are in small numbers, they are treated in specific centers. So, it’s not impossible and politically, sometimes we can feel a will to do this. We have law from 2015 that is a HTA law that gives conditions for that. So, what we need now is a real political will to do this, because this could be very useful in order to control the resources and to control the quality of the initial HTA analysis.

1.3. What are the roles patient organizations or advocacy groups have in orphan drugs?

These organizations are definitely becoming stronger. We have some examples of not just the formal advocacy patient associations, but also on social media. We have now an example of a new medical team for cystic fibrosis, where they add a strong pressure on social media in order to give access to these new products to a specific patient and, of course, to all the patients in the same situation. This is changing very quickly and the patient associations, or at least some of them, are becoming stronger, and this is a good thing, but there is also inorganic pressure coming from social media. This is not very easy to deal with when you are assessing this product for prices and reimbursement.

In Portugal we can give access to patients during the HTA assessment. We have a mechanism of special authorization for the use of these products within an access program specific for each product. This is the wide alternative access we have in Portugal. At the same time, we are doing the HTA assessment, and the decisions on the prices and the negotiation. That can take a long time, and this is the other problem. We are taking, in my opinion, too much time on this final decision to finance a new orphan drug.

1.4. What procedures are in place for the reimbursement of orphan drugs?

We have two mechanisms for ambulatory products or community use products through the community pharmacies, and this is the reimbursement. A percentage of the price is reimbursed by the NHS and through the NHS hospital, the old products are free for patients. Almost all of these orphan drugs are coming to the markets in Portugal go through the hospital. So, through hospitals, the rule is you will have to have a HTA assessment for each indication, and the NHS hospital can only use the product if this assessment is positive. If the assessment is negative, NHS hospitals, that are the hospitals that normally use these kinds of drugs, are forbidden to use it in that indication. So, it’s zero or one. If it’s allowed, the use of these kinds of products is free for a patient and this is the same rule that applies for all the products. So, there is no different treatment in terms of reimbursement for orphan drugs in comparison with the other kinds of drugs.

There is no specific budget for orphan drugs in Portugal, it’s within the same budget that they’ve used for all pharmaceutical expenses. I don’t think this will change in the future because of the way things work in Portugal. We tried in other circumstances, but the hospitals and the central organization that is the ACFS in the Ministry of Health are not very keen to have different bags for different products or diseases. There is just one budget for pharmaceutical products, and I think that it will not change. We discussed that, for instance for cancer and it was not possible. It’s a change in culture, and you know that to change the culture is not easy to do.

Section 2: Future Landscape

2.1. Which indications could benefit most from orphan drug therapies in the future?

If I recall well, oncology is the first one and the indications in oncology can be often very niches. For two, three, the drugs are classified as orphan drugs. And the second one that is very specific, of course is always amyloidosis. We have a genetic disease that was founded in Portugal and it now exists in all the countries where the Portuguese established colonies, like Brazil and some parts of the United States. However the large number of patients are still in Portugal, so it’s the second area in terms of costs in the orphan drugs. Like in any other country, there’s also more diseases that are always very expensive. So, I think that first is oncology, second is amyloidosis.

2.2. How are pharma companies looking to facilitate greater market access of orphan drugs in major healthcare markets?

Some pharma companies are doing everything they can. I think that for us there is a specific niche of product where some small companies are involved. Some biotech, some startups, and I felt that a difference between a product that is the marketing authorization although is a very well-established company with a lot of experience, and these new companies that are developing these kind of new products. Sometimes, from the regulatory point of view, they don’t have the experience, they are not very well used to the pharmacoeconomic assessment, and these can be also a reason for the pharmacotherapy and pharmacoeconomic access to be so long also because of the lack of preparedness of some of the companies.

I would say that in big companies that they have a lot of experience on these kind of things and the small companies that sometimes are the marketing authorization holders of these kinds of products. I personally felt the difference between these two. So, the small companies should be more prepared and to have a more responsiveness behavior to the demands of the HTA authorities. So, this is the only difference I could mention, but divided into small and big companies.

We have a tradition in HTA analysis. For community products, we are one of the first in Europe to do that. Since 2007, we started with the hospital medicines also doing HTA. So, we are applying the international methodologies in HTA. I’m not sure that we are rejecting more to finance more orphan drugs than other countries, what I’m saying is that because of this uncertainty, we are asking for more clinical data, more information, and sometimes if companies cannot provide the information that we are asking, so it’s taking more time than other product.

Our problem is not to reject more, it is to take more time. Then it is probably acceptable from the patient’s point of view. I’m not saying that we are rejecting more, we are taking probably more time, and we have to be very cautious on the decision and on the negotiation, because we don’t test all the tools we need to control the performance of the product and the cost effectiveness of the product because of the lack of good registry. So, we are being very cautious at the beginning. We are taking more time probably because of theft. I’m not saying that we are rejecting more products than other countries in terms of orphan drugs.

2.3. What will prove to be major bottlenecks to enable patient access to orphan drugs?

I wouldn’t say that that patients are offered cheaper treatments as opposed to orphan drugs because when you do an HTA and all you do is take this into consideration. You compare with the available alternatives when they are there, because in most of the cases in rare diseases, the products that are coming to the market are the first ones to treat the disease. So, I don’t believe that in Portugal the decision, if you can’t prove added value of the product, that the patients continue to be treated with a product less effective because of the price. This is a problem that we are facing because of the pressure on the budget but the rule is to recognize the added value of a product and to give access of the patients that are included on the approved indication.

I wouldn’t say that it’s in 100% of the cases, but the rule is to give access to the best treatment that is available and not to use the best treatment because the not-so-good treatment is cheaper. It’s not a problem, and this can creates a problem in terms of budget, but the rule is to give access to the best product once accessed and have a positive decision from the HTA.

The problem is that it’s very difficult to give access to the best product and feel the decision of reimbursement. This is linked to the personnel who helped this final decision on reimbursement. The problem is during this period of assessment and negotiation, but once the decision is taken, the patient will have access to them.