WFH  2018


WFH 2018

: cwaisman@netvision.net.il


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 R&D Conference Call(WFH 2018)HAVEN 3 _WFH2018pdfstudy / HAVEN 4 study results






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Frank Schnabel, the founder of the World Federation of Hemophilia (WFH), opened the first WFH Congress on June 25, 1963, with these words: “The threat to the life of just one haemophiliac would be sufficient reason for us to travel to this meeting. We are here, however, to help the hundreds of thousands of haemophiliacs by adding another organization which can be instrumental, in liaison with national societies.”

Over 50 years later, these words still ring true. The WFH is still focused on the idea of a community of people of action working to help the bleeding disorders community. This is the reason why thousands of people will come together in the name of Treatment for All at the WFH 2018 World Congress in Glasgow, Scotland, this May. By supporting our Congress, participants will be a community of action—and helping to back the many WFH-led programs that are shaping the evolution of bleeding disorders care.

As a global federation, the WFH needs to have a wide range of programs in order to support the many needs of the bleeding disorders community. Our programs cover government support, care delivery, medical expertise, distribution of donated treatment products, patient organization data collection, and outcomes research. The idea is that help is need in many ideas, so we need to invest our time and energy in many areas. This approach has allowed us to develop many programs that have helped to make a difference in our community, such as the Cornerstone Initiative, our many Country Programs, the Global Alliance for Progress (GAP), the Twinning Program, the IHTC Fellowship Program, NMO Training, IEQAS, and, of course, the Humanitarian Aid Program. These efforts have delivered measurable results. In 2016, WFH healthcare development programs and activities reached a total of 122 countries worldwide. From January to June 2017 alone, the Humanitarian Aid program was instrumental in delivering 97 million IUs of donated treatment products to people in need.

The WFH Congress is where stakeholders come together in the same place to help guide the decisions that will lead to future solutions. Be part of discussions that will impact the future of the bleeding disorders community. By attending the Congress, you’re supporting WFH programs, and joining a team of people who want to play an active role in the evolving world of bleeding disorders care. The many talks that happen during Congress are an opportunity for participants to learn about new developments in the industry and how they will impact the community. This is the way to have your voice heard.


We’ve moved from on-demand to prophylactic treatment with ever-increasing durations (of efficacy), and now to 24/7 coverage with gene therapy and novel agents

Glenn Pierce discussed a framework for establishing a gene therapy knowledge base, including known unknowns, such as high variability of protein production and the consequences of integrating DNA into the genome

Glenn Pierce briefly touched upon gene editing and cell therapy, and showed data demonstrating the feasibility of these technologies

Gene therapy is really exciting. Since 2015 we’ve seen therapeutic levels of factor IX and factor VIII being achieved in a small number of patients, and those levels have relieved them of their dependence on exogenous replacement therapy

In gene therapy, we really need to continue research. There are far too many unanswered questions. We shouldn’t forget that this is an early technology

Prophylaxis is currently the gold standard for hemophilia treatment

The earlier it is started the better the results, but the complexity of prophylaxis may influence adherence to treatment

Extended half-life (EHL) products have shown the potential to overcome this problem. Real-world clinical evidence of prophylaxis with factor VIII (FVIII) EHL products indicates that 30 to 40 per cent less infusions are necessary, which equates to 20 to 30 per cent lower consumption of FVIII. For factor XI (FIX) EHL products, the data are even more promising with 55 to 65 per cent less infusions necessary, equating to 40 to 60 per cent lower FIX consumption

A move towards personalized medicine will increase treatment complexity, because it will be necessary to identify the correct product, patient, dosing and timing

The latest FVIII products may show differential immunogenicity due to new non-wild-type amino acid sequences and non-wild-type post-translational modification

a 20 to 43 per cent incidence of inhibitors has been reported in trials of previously untreated patients receiving standard recombinant FVIII products

Of an estimated 490,000 people living with hemophilia worldwide, 57,000 receive more than 4 international units (IU) per capita treatment. To treat this population would require 40 billion IU per year. To provide prophylaxis to 10 per cent trough levels would require 792 billion IU per year


Extended half-life (EHL) products have the potential to reduce the frequency of infusions required to maintain factor to the trough levels achieved with standard half-life products

Pasi highlighted the potential safety issue with PEGylated proteins in EHL treatments. “Polyethylene glycol (PEG) is generally not easily biodegradable, it is either metabolized by oxidization of alcohol groups or by urinary clearance,” stated Pasi. “Metabolism by these mechanisms can in theory pose toxicity problems.” However, PEG has a large therapeutic index and there have not been any safety signals in clinical trials to strongly suggest cause for concern.

Emerging therapies such as bispecific antibodies, RNA silencing therapy, anti-tissue factor pathway inhibitor and gene therapy will completely change the market again

One of the biggest problems facing women with a bleeding disorder is heavy menstrual bleeding affecting nine out of ten women. In addition, women with a bleeding disorder tend to bleed for longer and experience heavier bleeding

Many treatment options are available to women with heavy menstrual bleeding. However, barriers to accessing healthcare exist for these women, in part due to reluctance to accept their condition or to approach their doctor about this health issue

Certain cultures and religions impose many restrictions on women who are menstruating because they are viewed as impure. However, some societies—such as the Maori society in New Zealand and some North American tribes—consider menstruation to be sacred


Patients want a normal life, healthcare providers aim to optimize treatment and payers work towards reducing costs

ultrasound and magnetic resonance imaging techniques are increasingly used to detect changes in the synovium and cartilage in the absence of bleeding.

The future looks bright for hemophilia

prophylaxis has brought great advances in the treatment of hemophilia, particularly severe cases in which an increase in trough level to two or three per cent results in a dramatic reduction in bleeding

the need for treatment to be individualized according to age.

There is pharmacokinetic variability between products, so you must take this into account and dose accordingly

up-and-coming therapies, including the promising drugs emicizumab and fitusiran, both of which are in clinical development. The subcutaneous route of administration of these drugs will further facilitate treatment, and the recent explosion of new products for hemophilia will make it easier to individualize treatment and lower the disease burden.

the exciting area of gene therapy, focusing on two recently published early-stage clinical trials of gene therapy in hemophilia A and B. These trials demonstrate that gene therapy brings about sustainable levels of factor VIII and factor IX. However, immune response to the adeno-associated viral vector remains an issue for the majority of patients and therefore alternatives are needed

he (WFH president) implored pharmaceutical companies to not allow legal feuds hinder access to innovative treatment

Hemophilia is a brand name! VWD and other rare bleeding disorders need the same level of exposure, because no one with a rare bleeding disorder should have to make tough decisions


gene therapy for people with hemophilia include interpatient variation in factor expression, response durability, safety considerations and risk of inhibitor development. Whether the procedure is applicable to children, people with inhibitors, and/or those with a preexisting immunity to the adenovirus-associated viral vector (AAV), including people who already received gene therapy for hemophilia, still needs to be addressed.

Mechanisms to enhance factor IX expression are being explored for hemophilia B. Methods include adding a promoter, modifying the vector to remain undetected by the immune system, and incorporating the highly active Padua variant of factor IX.

Gene therapy is more challenging for hemophilia A due to bottlenecks of factor VIII production at the transcriptional, translational and post-translational level,” said VandenDriessche. However, a pivotal clinical trial using codon-optimized AAV serotype 5 recently published promising results in men with severe hemophilia A.

VandenDriessche ended the session on lentiviral vectors, a promising technology with several improvements over AAV. Current lentiviral vectors have the potential to sustain factor expression long-term since these are liver-directed therapies and pre-existing immunity is not an issue.