Independent Consultant and previous President
French Drug Transparency Committee
Bernard is a consultant in market access and reimbursement. He is a visiting professor of epidemiology and public health at the Université de Liège and previously served as President of the Transparency Committee in France providing advice to the Ministry of Health and Social Affairs for drug listing and pricing. He is also a member of the Medical Device reimbursement committee at the HAS as representative of Devices Industry (SNITEM).
Section 1: Current Landscape
1.1. How would you describe the current market access landscape for IBD/Colitis therapies globally?
Both ulcerative colitis and Crohn disease are very severe in their condition. They are both chronic inflammatory diseases with a relatively high level of morbidity complication for the patient, and where there is sometimes a need for surgery. There are very tough side effects in Crohn’s disease like fistulae, and the symptoms can be very unpleasant. The background quality of life is high, and there are several lines of treatment. Despite the availability of different therapeutic options in first-line, second-line, third line, there is still a need to have a new effective drug. The outcomes today are probably more around the avoidance of morbidities and the avoidance of surgery. This is more than a simple improvement of symptoms, because you have a lot of products for that and there is still room for new therapeutic options.
The situation in France in terms of reimbursement and market access in the domain of IBD is very specific and the situation of IBD is different from rheumatoid arthritis or psoriasis, even though it is the same products.
For example, in psoriasis, a cutaneous inflammatory chronic disease, we have the same lines of treatment. First methotrexate, as a first-line, biologics and then second-line, biologics such as JAK inhibitors. The position of each drug is different from other chronic diseases. The reason is because of the Transparency Committee, gave for each new product an ASMR in comparison with a specific drug. Probably it is linked to the development of these drugs and the clinical trials conducted for the new drugs. For example, ustekinumab obtained ASMR IV against Enbrel and COSENTYX obtained ASMR IV against ustekinumab. We have specific positioning, biologics are only for in the biologic line, not for a naive patient of biologics. In the rheumatoid arthritis for example, JAK inhibitors are placed in the last line after biologics. In the absence of direct comparison with the biologics, we have the position of JAK inhibitors which in this case are, in the therapeutic strategy, the last option. For IBD when we only have a placebo comparison, for example it was the first evaluation of ENTYVIO or the recent evaluation of ustekinumab or tofacitinib. In this case, these news drugs are not reimbursed as the ASMR is insufficient in the naive population.
When the Transparency Committee, can evaluate comparative clinical studies, they can change the position in the therapeutic strategy. It is the case for ENTYVIO, the first evaluation in ulcerative colitis was third line only for the patient previously treated by the TNF inhibitor. After the comparative clinical trial and clear superiority against adalimumab, in this case ENTYVIO is also reimbursed in the first-line biologic as an alternative to the TNF inhibitor. Explaining that in some situation, if you’re patient is very severe, the first choice remains TNF inhibitor and maybe REMICADE. If we have some characteristics, we have also to favorize TNF inhibitors and the other JAK inhibitors and ustekinumab are only in the third line, after the first-line biologics. So JAK inhibitors can be last line in the therapeutic strategy but reimbursed as an alternative to biologics. In IBD it is different to rheumatoid arthritis and different in psoriasis.
In the case of REMICADE, it is a hospital drug, restricted to use in hospital. When we have the possibility of subcutaneous administration, it is the case of the vast majority of biologics, TNF inhibitor or ustekinumab, and it is possible to use the drug for outpatients. There is no difficulty to fund the drug, because in hospitals we need to be outside the DRG to be funded; all JAK inhibitors are oral treatment.
1.2. What are the current types of reimbursement schemes used for IBD/Colitis therapies?
No, in France we don’t really have a specific budget. Despite some priorities in terms of anti-cancer or it’s Alzheimer plan, but all these priorities are mainly for the diagnostic of the disease. Drugs are only evaluated by the Transparency Committee, and the price is negotiated by the Economic Committee within a fixed envelope with a specific budget. It is the whole budget for all drugs, and each year the parliament votes to increase the envelope by 1% or 2%. The main job of the Economic Committee is to find room for new and innovative drugs among all the other drugs, without a specific budget. There was only one case, where there was a discussion for a hepatitis C drugs because everybody was afraid about the budget impact and there was a specific budget, but not for the other drugs.
1.3. How successful have IBD/Colitis therapy market penetration attempts been?
The general rules are mainly based on the pertinence of the comparisons. Unfortunately, a lot of these new drugs only had a placebo comparison. We can understand that the philosophy of the Transparency Committee is you have several therapeutic options on the market and reimbursed in this indication, with a placebo comparison it is impossible to place the new drug in the therapeutic strategy in a specific line of treatment. By definition, we need to know that this new drug is at least as effective as the drug we have in the same line of treatment. The rule is if we have no comparison, we put the drug after. In case of failure of the previous line of treatment, but we have more and more drugs in each line of treatment. It is more and more difficult to have a precise position, but clearly it is based on the comparison.
We also have a specific point which is for biologics because in France the first biologics for rheumatoid arthritis were developed 20 years ago, but it remains always the same precaution. All biologics are only for severe patients and the second-line treatment, and biologics can never compete with methotrexate for first-line or this kind of very common standard of care for non-severe first-line patients.
Section 2: Future Landscape
2.1. How will market access strategies change for IBD drugs?
I don’t see any changes, for several reasons. Firstly, the process for the reimbursement with the first evaluation by the TC, is a price negotiation with the Economic Community. We represent Ministry of Health finance and national insurance. It really is a very old procedure and there was in recent past, some attempts to change it. Nothing happened after five years of the time to achieve change in the criteria and the system. Recently in August, a new decree, fixed the procedure. This is the same in Germany and also other European countries. It is a price negotiation based on the comparator, after an evaluation of the value of the drug, and the decision of reimbursement is finally the success of price negotiation.
In France, we have no true decision for the reimbursement. It is a positive recommendation by the TC, but it is only a recommendation. If the manufacturer doesn’t find an agreement for the price, the drug is not reimbursed, and the non-reimbursement is the failure of the negotiation. I don’t see any change in the future.
2.2. How are pharma companies looking to facilitate greater market access of IBD/Colitis in major healthcare markets?
There is clearly a gap between the expectation of the pharmaceutical company and the French health authorities because the trend is to ask for more and more documentation about the most clinical pertinent outcome. For them, real world is not very robust, and it is not possible to compare the products using real world data. They don’t believe that real world evidence exists, and I have never seen an improvement of the ASMR based on the real-world evidence. With PROs there is maybe a change in this attitude. If PROs means quality of life evaluation, there is a trend to take into account quality of life in the evaluation of the added benefit, but the rules are so strict because quality of life need to be included in a randomized, double-blind clinical trial. This considers an efficacy outcome, in fact in complement to the robust clinical endpoint.
In the future, I suppose the pharmaceutical company will have to document the possibility to have a complete healing, avoidance of surgery and complete remission in terms of symptoms, morbidity and so on and the weak evaluation cannot fill the gap.
2.3. How will reimbursement models evolve to better accommodate costly IBD/Colitis therapies?
It will be probably the general pathway for the reimbursement but in addition, all biologics are in a specific procedure for the prescription and the reimbursement. This procedure does not facilitate the access for the patient because exceptional medicines means restriction to specialists, mainly first prescription by hospital doctors. The first prescription has to be exactly in, according the recommendation of the Transparency Committee and the prescription is a specific form. There is in theory, a possibility to have a control of the prescription to avoid the extension of the use of biologics. Mainly because the reimbursed indication is a narrow indication, restricted indication in the label. Often the level given by EMA is a broad indication and the reimbursed indication is more limited with the need of this procedure to be sure to control the prescription.
2.4. What will prove to be major bottlenecks to enable patient access to IBD/Colitis drugs?
For biologics, if biologic treatments are drug restricted to hospital use or if it is a drug available in retail pharmacies, because it is a subcutaneous administration in hospital and it is in practice only for REMICADE, it is an infusion and it is a hospital drug. When the first biosimilars came on the market, the decision to impose biosimilars can be taken by the pharmacist of the hospital in the drug committee of the hospital. There is no choice for the prescribers, the pharmacists organize tenders. But it can depend it is different from one hospital to another, and the pharmacist can impose a biosimilar. It is in this case, there is no difference between a classic generic and a biosimilar.
For the biologics available for outpatients, it is different because the pharmacists out of the hospital cannot switch a biologic treatment, it is only possible to switch if it is the first prescription. However, in retail pharmacy, pharmacists do not know if it is first prescription or not and to be sure, the prescription of biosimilars is under the control of the doctors. From this kind of biologic, there are some incentive to favorize the prescription of biosimilars by specialists. In a hospital if they prescribe in a certain proportion, the hospital receives an incentive. Finally, the main change in the therapeutic strategy is the use of the biosimilar instead of the originator but there is no impact on other drugs in the same line of treatment or other line of treatment. In France is not because we have a cheaper alternative that we use extensively the drug, because the cost is low. Each drug is chosen, as a physician choice.
From the perspective of the Transparency Committee, the unmet need is based on the severity of the disease and the number of therapeutic options. In other word if it is severe and if we have no treatment, then there is a very high unmet need. The wording of the committee is that the unmet need is, “Not covered.” If the disease is less severe and if we have a different therapeutic option, the unmet need is partially covered. As I said before, because it is a chronic inflammatory disease, all new drugs are welcome. We need to change the treatment because IBD are disease of the life, for the life and we need a lot of therapeutic options.