New Technologies in Treatment 2023

New developments in non-replacement therapy, rebalancing therapy, gene therapy or artificial intelligence. These and other topics were discussed at the workshop on new technologies in the treatment of rare bleeding diseases, held in Lisbon, Portugal, November 3-5, 2023.

Non-replacement treatment

This type of treatment has attracted the most attention from our community for several years, and rightly so. It is a type of treatment in which the missing factor is not added to the patient's body, but other substances that can replace its function in the blood clotting cascade. The main advantage of this type of treatment is that it is administered by subcutaneous injection with relatively long intervals between doses (1, 2 or 4 weeks).

Emicizumab is currently available on our market for the treatment of severe haemophilia A, including for patients with inhibitors against standard factor VIII. This product can produce the same effect in the body as if a person had a factor VIII level of 10%-15%, without any fluctuation between doses.

At the moment, research is being conducted into the use of this product in other patient groups - specifically, in women with haemophilia A, and in patients with moderate or mild haemophilia A. Although the available data is very limited for these patient groups, analysis of the data so far suggests that this product may be suitable for them as well.

Similarly, the results of early studies suggest that this product could also be effective for patients with von Willebrand disease types 2N and 3.

The development of a completely new generation of drugs of this type is also under way. While the first generation substance was 90% humanised and could thus cause an immune system reaction in rare cases, the second generation products are already completely adapted to the human body.

The furthest along is Mim8, which is now in phase 3 clinical trials and, if all goes to plan, could be approved for use by the end of next year. Compared to Emicizumab, it should allow even smaller volumes of drug to be administered and should have an effect level of about 20%-30% by a factor of about 20%.

Another promising agent is NXT007, which has now completed trials in healthy populations. It promises a half-life (the time it takes for the amount of active ingredient in the patient's body to drop by half) of up to 10 weeks and corresponding factor levels of up to 30%-40%. It is currently in phase 1/2 clinical trials.

Rebalancing treatment

Products in the rebalancing treatment category have a completely different mechanism of action, based on lowering the level of anti-clotting agents in the patient's body. We have explained their mechanism of action in more detail in an article about last year's workshop.

While Concizumab is expected to be approved in the first half of next year, Fitusiran has seen an extension of phase 3 clinical trials. These will be the first subcutaneous products that will also be effective in haemophilia B. However, their mechanism of action may, in rare cases, carry an increased risk of thrombosis, so physicians can be expected to take a very cautious approach to the indication, taking into account the history and needs of the individual patient.

The third product in this category is SerpinPC, which is currently in phase 2 clinical trials. It is certainly worth further monitoring, as it could be the option with the fewest potential side effects in this category of drugs.

Prophylaxis for von Willebrand disease

Compared to last year, there has been an increase in the amount of information on products for patients with von Willebrand disease. In addition to the aforementioned study on the possible use of Emicizumab, completely new agents are currently under investigation that could offer comparable convenience in terms of administration method (subcutaneous injection) and dosage.

Among the agents mentioned were KB-V13A12, SyntoPlates and VGA039. Their research is still at a rather early stage of laboratory trials.

Other rare bleeding disorders

There is also hope for patients with rarer bleeding disorders such as Glanzmann's thrombasthenia. A substance called HMB-001 is now in phase 1/2 clinical trials that could act as a prophylaxis for patients with this disease.