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2016 Annual Minutes
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6/8/2016 at 5:25:13 PM GMT
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2016 Annual Minutes

FVIII/FIX/Rare Bleeding Disorders SSC Minutes

Chairman: Guy Young

Co-Chairs: Manuel Carcao, Gili Kenet, Johnny N. Mahlangu, Michael Makris, Danijela Mikovic, Elena Santagostino 

Top Abstract

Vincent Muczynski

Dr. Muczynski presented the top abstract from the SSC abstracts relevant to our program. He described the development of a FVIII nanobody molecule which incorporates a nanobody that has a prolonged binding interaction with VWF thus prolonging the half-life of FVIII by approximately 2-fold.


Project updates

Inhibitor Reporting Standardization in Previously Treated Patients

Alfonso Iorio

Dr. Iorio reported on the progress of his working group which developed guidelines for how reports on new inhibitors in PTPs should be reported in the literature. The project is complete and the manuscript regarding the recommendations are now published in JTH.

Bleeding Score in Hemophilia

Maria Elisa Mancuso

Dr. Mancuso reported preliminary results on development of bleeding score in patients with hemophilia. Thus far 319 patient’s data have been collected however preliminary data suggest that there is some correlation based on ROC curves however more patients data needs to be collected to improve the score. A call was made to get more centers involved.

When and how to start prophylaxis in boys with severe hemophilia without inhibitors

Kathelijn Fischer

Dr. Fischer reported that the working group completed its work and the recommendations from the group on when and how to start prophylaxis in boys with severe hemophilia A without inhibitors has now been published in JTH.

Standardization of post-registration surveillance

Flora Peyvandi

Dr. Peyvandi described the mandate of the group which is to develop methods for long-term safety/efficacy of novel long-acting factor products (or even other products) for hemophilia. The project involved setting up a minimum dataset for what should be collected after licensure of new drugs. Currently, the dataset is posted on the ISTH website for comment.

Consensus Definitions for Immune Tolerance

Elena Santagostino

Dr. Santagostino reported on the progress of her working group describing the definitions for achievement of immune tolerance.

The work is nearly complete and a manuscript is in preparation.

Working group on pharmacokinetics and population pharmacokinetics of factor concentrates

Alfonso Iorio

Dr. Iorio described the formation of this new working group whose goals are to describe the manner of reporting study results in the literature, interpretation of the results of PK and PopPK studies, assessment of PK/PopPK in clinical practice, and suggestion of study design for clinical trials that include PK/PopPK.

Definitions in Acquired Hemophilia

Andreas Tiede

Dr. Tiede described the formation of this new working group whose aim is to develop a set of definitions for acquired hemophilia. His report demonstrated that previous registries report various definitions for success of treatment and time to success of treatment among other variables.


Gene Therapy Session 

Definitions of Outcomes in Gene Therapy

Alok Srivastava

Dr. Srivastava described several issues for consideration with respect to reporting outcomes in gene therapy trials both for efficacy and safety. Efficacy should include peak and sustained factor levels and control of bleeding. Questions remain about what should be considered efficacious with respect to what levels should be achieved long-term for a product to be licensed. For safety, issues of insertional mutagenesis, immunotoxicity and horizontal and vertical transmission of vector. Dr. Srivastava suggested that a working group should be formed to discuss these issues with regulators, industry and academia involved.

Regulatory guidance for gene therapy trials

Annelise Hilger

Dr. Hilger reviewed issues that are related to regulatory aspects of gene therapy in particular that the usual guidelines for approval of factor concentrates cannot apply to gene therapy trials.

Gene therapy: From clinical trials to clinical practice

Steve Pipe

Dr. Pipe reviewed recent results from published clinical trials including abstracts and compared and contrasted what might be achieved from the current gene therapy trials versus the extended half-life drugs and other new compounds and speculated on where the role of gene therapy might be in the future with respect to other compounds in development.


SIPPET session

Presentation of SIPPET data

Flora Peyvandi

Dr. Peyvandi presented the results of the SIPPET study which coincidentally was published in the New England Journal of Medicine the day before the session.

Debate on the SIPPET study

Manuel Carcao and Kathelijn Fischer

Drs. Carcao and Fischer debated whether or not PUPs should be started on recombinant or plasma-derived factor products. This was followed by a discussion between the audience and the speakers. It was a robust debate the suggested the need for a “Debate-type” paper in JTH.

Stakeholders discussion on SIPPET results

Brian O’Mahony (patient), Marijke van den Berg (WFH), Stephanie Seremetis (Industry-recombinant), Garrett Bergman (Industry-plasma), Annelise Hilger (Regulatory)

The above each discussed the SIPPET results (those from the abstract from ASH) from the perspective of the groups they were representing. This was followed by a discussion between the audience and the speakers.


Rare Bleeding Disorders

European Network on Rare Bleeding Disorders Report on FXIII

Flora Peyvandi

Dr. Peyvandi describe the work of this network describing the risk for bleeding as related to the FXIII level in patients with FXIII deficiency. The research demonstrated that patients with severe FXIII deficiency are generally diagnosed at 5 years of age however often have their first bleeding symptom in the first year of life. In addition, severe bleeding is noted for patients with levels below 20%.

Next Generation Testing for Rare Bleeding Disorders

Diane Nugent

Dr. Nugent reported her work on next generation sequencing for rare bleeding disorders. She stated that with this method, she identified a number of previously unreported mutations. In addition, this method allows for the identification of co-inherited mutations that could influence the bleeding phenotype.

Plasminogen deficiency

Amy Shapiro

Dr. Shapiro described the background of plasminogen deficiency as well as provided an update on clinical trials of plasminogen concentrates and plasminogen eye drops for ligneous conjunctivitis, the major manifestation of severe plasminogen deficiency.

Extended Half-life Factor Products

Laboratory issues with the extended half-life products

Steve Kitchen

Dr. Kitchen described the publications and abstracts regarding the measurement of recovered factor from various extended half-life products demonstrating that there are inaccuracies in measuring recovered factor depending on the product and PTT reagent combination. He also demonstrated that much of these errors can be averted if the chromogenic factor assays are adopted. The discussion led to the suggestion to form a working group to develop an SSC recommendation regarding the chromogenic assay.

Debate on the use of extended half-life FVIII therapies

Amy Dunn

Gerry Dolan

Drs. Dunn and Dolan debated the merits of switching patients from standard half-life factor VIII products to extended half-life products. The debate was followed by a vigorous discussion.

Debate on the use of extended half-life FIX therapies

Johnny Mahlangu

Charlie Hay

Drs. Mahlangu and Hay debated the merits of whether all patients with FIX deficiency who require factor should switch to extended half-life factor IX products. The debate was followed by a vigorous discussion.


Inhibitor session

Framing the inhibitor problem

Donna Di Michele

Dr. Di Michele discussed several issues with regards to inhibitors including inhibitor development, prediction as well as treatment and prevention of bleeding. Her discussion set up the rest of the session by framing the major issues facing inhibitor patients.

SSC Inhibitor Collaborative Study on the South Mimms Inhibitor Assay

Sanj Raut

Dr. Raut presented data on a novel method for the detection of inhibitors in patients with hemophilia. His goal is to develop a collaborative study to further validate this assay. He presented the protocol and will solicit other participants from the community.

Alternative treatment options using current therapies

Gili Kenet

Dr. Kenet described alternative approaches to treat bleeding in inhibitor patients including using sequential/combined therapy with rFVIIa and FEIBA as well as using FVIII along with bypassing agents.

Future therapies for patients with inhibitors

David Lillicrap

Dr. Lillicrap provided an overview of 3 new products in clinical development that are in current human trials: ACE910 (emicizumab), ALN-AT (fitusiran) and the anti-TFPI product concizumab.

Inhibitor Management in 2020

Guy Young

Dr. Young moderated a session discussing how inhibitor patients may be treated in 2020 with the assumption that novel agents such as ACE910 (emicizumab), ALN-AT (fitusiran) and anti-TFPI products. The discussion revolved around management of PUPs, immune tolerance induction, and treatment/prevention of bleeding.

Last edited Wednesday, June 8, 2016
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