The European Haemophilia Consortium (EHC) releases today another edition of its newsletter on ‘Novel treatments in haemophilia and other bleeding disorders: A periodic EHC review. This publication comes ahead of the EHC’s 32nd scientific conference taking place on 4-6 October in Skopje, North Macedonia.

Through this document, prepared by the EHC New Products Review (NPR) Committee, the EHC wishes to provide its members with accurate, up-to-date and easy-to-understand information covering the latest therapeutic developments for rare bleeding disorders.

The information is collected via scientific, medical and financial publications but also by attending scientific and medical meetings. For instance, this issue draws most of its content from information disseminated during the last Congress of the International Society of Thrombosis and Haemostasis (ISTH), the 10th BIC International Conference (which this year was held in conjunction with the 3rd Inhibitor Conference) and the National Hemophilia Foundation (NHF) Workshop on Novel and Gene Therapies. Pharmaceutical companies can also submit publicly-available information such as press releases, scientific posters and publications to the committee.

This document is independently compiled and reviewed by the committee, and final content decisions are taken by the EHC. Readers should note that the content of this newsletter is for informative purposes only and that it does intend to provide medical advice or to endorse any specific medicinal products.

To share a flavour of this publication, we interview Declan Noone, one of the NPR Committee members. We ask Declan what readers should look out for in this 26-page document!

Laura Savini (LS): Declan, in your opinion, what are the most significant developments that occurred since our last issue in January 2019?

Declan Noone (DN): A couple of things have stuck with me. To begin with, the progress made in gene therapy. We have all heard that gene therapy may be five years away. Now, we are looking at the first gene therapies filing for licensing in Europe and the United States by the end of the year. If this goes as planned, we may be starting to see the first gene therapies on the market in 2020/2021. Besides it being so eagerly anticipated by the community, it raises so many questions. What about long-term monitoring for factor expression and unknown side-effects? How long will this therapy last? What are the factors that could promote higher and longer expression? What factor levels should be targeted? And, last but not least, what about pricing? We recently saw in the news, cases of parents fundraising massive sums of money for gene therapy in other therapeutic areas (see the story of Pia in Belgium and Kris in Slovenia). We also saw countries, like the United Kingdom, struggling to reach agreements with companies on the prices of novel, innovative treatments. Will it be different for gene therapy in haemophilia? I think that besides keeping an eye on the medical evidence, we need to prepare as a community to be actively involved in discussions related to access to all novel treatments that will improve the quality of patients and reduce the burden of treatment. We will also need to measure these endpoints appropriately.

LS: Okay, so definitely read the gene therapy section! What about other treatments that have caught your eye?

DN: I was really interested to see companies starting to explore the use of gene editing and cell therapy in haemophilia. Both of these technologies are still in the early stages for haemophilia, but I think it will be interesting to see where it goes. We have also had quite a bit of progress with non-replacement therapies. For example, we now see emicizumab being used in Europe more widely in haemophilia A patients without inhibitors. It was also great to see results of other non-replacement therapies that rebalance the general haemostasis, such as concizumab, fitusiran, marstacimab and serpinPC.

LS: We talk a LOT about haemophilia. Is there any news for other rare bleeding disorders?

DN: The good news is that, in theory, non-replacement therapies that rebalance the general haemostasis could be used in some factor deficiencies dependent on where they fall in the clotting cascade. Unfortunately, though, clinical trials are only being conducted, for now, in haemophilia A and B with and without inhibitors. We also saw the first marketing authorisation for a recombinant von Willebrand Factor that can be used in bleeding episodes and during surgery in patients affected by von Willebrand Disease, with prophylactic license coming in the near future.

LS: In this newsletter, we also try to give our community some food for thought. We raise some topics that patients should think about regarding novel therapies. You’ll recall in the last issue we had a comment on gene therapy. What are we looking at in this issue?

DN: In this issue, we are looking at gene therapy and the use of PEG (Polyethylene glycol) in novel therapies.

For gene therapy, we look at the factor expression over time. During the recent NHF meeting, speakers made some interesting hypotheses about what could influence the loss of expression over time, and we wanted to share these with our community.

If you’ve read our previous issues, you’ll know that PEG helps to extend the half-life in replacement therapies. First of all, we see some differences in terms of approval between American, European and Australian regulators, so we wanted to make our community aware of that. Secondly, and this is not new, we consider the question of what the long-term effects of PEG accumulation in the body might be. PEG is used daily by millions of people, and the molecule is found in all sorts of products. However, never before has it been used in an intravenous product that needs to be potentially used for decades. The question is whether PEG accumulates in the body. If so, where? And does that have any consequences on the user’s health? We do not know. This is why it’s so important to collect long-term data. I want to make it clear that we are not saying that PEG is unsafe; we are just wondering about the effects of its long-term use. I think it’s a legitimate question, especially for people who will be using the treatment long-term.

LS: Okay, we’ve covered a lot of ground. Any final word to our readers? Where can they get even more information?

DN: For our readers attending the 2019 EHC Conference this weekend, I will say this: Do not miss the Saturday session at 10.15 on Quality of Life and Patient Experience on first available non-replacement therapies. I also recommend you attend the Sunday session at 8.30 on gene therapy. I know it’s early, but it will be worth your while. Also, come to the EHC booth during the Sunday coffee break (10.15 to 10.45), you will be able to meet some of the NPR Committee members and ask any questions you have. Finally, if you are a member of EHC National Member Organisations (NMOs), you can get in touch with your NMO to see whether you can register to our Workshop on Novel Technologies in Haemophilia Care, taking place on 22-24 November in Athens. During that workshop, we will cover a lot of the topics covered in the newsletter, and you will be able to meet and ask questions to experts in this area. Registrations end on 20 October.

Thank you, Declan, for your insight on the newsletter. Till the next edition.

Read previous issues of the newsletter: