Top 10 Hemophilia Stories of 2019

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Hemophilia News Today brought you daily coverage of important discoveries, treatment developments, clinical trials, and other key events related to hemophilia throughout 2019.

As we look forward to bringing you more news in 2020, we would like to remind you of the 10 most-read stories of 2019.

No. 10 – “First 2 Adults with Severe Hemophilia A Respond Well to Gene Therapy in Clinical Trial

The first two patients with severe hemophilia A treated in a Phase 1/2 trial (NCT03588299; 2017-000806-39) testing the safety and tolerability of BAY 2599023 responded favorably to treatment, Hemophilia News Today reported in December. BAY 2599023 is an investigational gene therapy developed by Bayer in collaboration with Ultragenyx Pharmaceuticals.

The study, which is still recruiting participants, is expected to enroll approximately 30 adults with severe hemophilia A from several sites across the U.S. and Europe.

The experimental gene therapy uses a viral vector to deliver a shorter but functional copy of the FVIII gene to liver cells, where clotting factors are produced. By doing so, BAY 2599023 restores the production of clotting factor VIII (FVIII), which is missing in people with hemophilia A.

Early findings from the trial — presented by the company in a poster at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition — showed the therapy safely increased the levels of FVIII in the blood in the first two men treated in the trial. It also lowered the number of, or prevented, spontaneous bleeding episodes in those two patients.

No. 9 – “FDA Approves Esperoct as Prophylactic Treatment for Hemophilia A, Novo Nordisk Says

In February, Hemophilia News Today covered the approval of Esperoct (turoctocog alfa pegol), also known as N8-GP, as a prophylactic, or preventive therapy for people with hemophilia A. The therapy is approved both to reduce the frequency of bleeds and for on-demand use to control bleeding episodes in hemophilia A patients.

Esperoct, an engineered formulation of FVIII developed by Novo Nordisk, has been designed to enhance the stability of FVIII to improve blood clotting.

The decision by the U.S. Food and Drug Administration (FDA) to approve Esperoct was based on clinical data collected from 270 children and adults with severe hemophilia A who participated in a series of Phase 3 trials — NCT01731600, NCT01480180, NCT01489111, NCT03528551, and NCT02137850.

When given as a single injection at a fixed dose every four days in adults and teenagers, and every three to four days in children, Esperoct proved to be an effective routine prophylactic to prevent bleeds. The medication also was found to be effective at managing bleedings prior to surgery.

No. 8 – “Cell-based Gene Therapy May Offer Long-term Treatment for Hemophilia A, Mouse Study Suggests

In a pivotal study published in the journal Stem Cell Research & Therapy last January, researchers reported that cell therapies based on endothelial progenitor cells and stem cells genetically engineered to produce functional FVIII could become stable and long-term treatments for hemophilia A.

The investigators showed that by transplanting cells isolated from human placenta and umbilical cord blood that had been engineered to produce functional FVIII, they could relieve the symptoms of mice with a hemophilia A-like disorder.

They also found that transplanting both cell types simultaneously led to a stable and long-lasting engraftment of cells in the animals. This was an important finding, as cell-based therapies hold promise for the treatment of hemophilia A, but have been hampered by the fact that transplanted cells do not remain inside the human body for long periods of time.

No. 7 – “Hemlibra Superior to Factor VIII Therapies in Hemophilia A Patients Without Inhibitors, Trial Data Show

Investigators from Roche reported in August that preventive treatment with Hemlibra (emicizumab) is superior to replacement therapy with FVIII infusions in reducing the frequency of spontaneous bleeding episodes in people with hemophilia A without inhibitors.

Their findings, from a pooled analysis of four trials — A-LONG (NCT01181128), LEOPOLD II (NCT01233258), SPINART (NCT00623480) and HAVEN 3 (NCT02847637) — were published in the journal Current Medical Research and Opinion. The analysis showed that, when given preventively, Hemlibra was able to reduce the frequency of spontaneous bleeds by 64% compared with FVIII infusions.

Roche’s Hemlibra is a humanized monoclonal antibody approved in the U.S. as a routine preventive treatment for adults and children with hemophilia A, with or without FVIII inhibitors. The medication also has been approved in Europe as a preventive treatment for all hemophilia A patients with inhibitors, and for those with severe forms of the disease with or without inhibitors.

No. 6 – “Hemlibra Approved in Europe to Prevent Bleeds in Hemophilia A Patients Without Factor VIII Inhibitors

In March, Hemophilia News Today covered the approval in Europe of Roche’s Hemlibra as a prophylactic treatment for patients with severe hemophilia A of all ages without FVIII inhibitors. 

The European Commission’s decision to approve Hemlibra was based on data from two Phase 3 trials — HAVEN 3 (NCT02847637) and HAVEN 4 (NCT03020160) — that showed the therapy’s strong potential to manage bleeds among those with hemophilia A.

In HAVEN 3, which evaluated the therapy in 152 adults and adolescents with hemophilia A without factor VIII inhibitors, Hemlibra reduced all bleeding episodes by 96–97% compared with no preventive treatment, when administrated prophylactically once a week or every two weeks.

In HAVEN 4, which enrolled 48 adults and adolescents with hemophilia A with and without FVIII inhibitors, more than half (56.1%) of those treated with Hemlibra over a period of 24 weeks experienced no spontaneous bleeds. Meanwhile, 90.2% of participants had three or fewer bleeds.

Hemlibra had previously been approved by the FDA as a routine prophylactic therapy for those with hemophilia A without FVIII inhibitors.

No. 5 – “Gene Therapy for Hemophilia A, SB-525, Showing Continued Benefits in Trial Data Update

A single infusion of SB-525, an investigational gene therapy now in development by Pfizer, led to stable and clinically relevant improvements in FVIII, Hemophilia News Today reported in June. Researchers said the treatment could reduce the need for replacement therapy in patients with hemophilia A.

These preliminary findings came from follow-up data from the first eight participants given ascending doses of the therapy in an ongoing open-label, Phase 1/2 trial (NCT03061201) sponsored by Sangamo Therapeutics, which has now transferred its Investigational New Drug application to Pfizer. The findings were presented at the 2019 Congress of the International Society on Thrombosis and Haemostasis (ISTH) in Melbourne, Australia.

SB-525 uses a viral vector to deliver a functional copy of the FVIII gene to liver cells, where clotting factors are produced. By doing so, the therapy seeks to restore the production of FVIII in a long-term basis, thereby eliminating the need for FVIII replacement therapy.

The therapy had previously been granted both fast track and orphan drug designations by the FDA, which supported the launch of the dose-ranging, Phase 1/2 clinical trial now underway.

No. 4 – “Potential Gene Therapy Safely Restores FVIII Clotting Factor in Animals and Human Cells, ASC Therapeutics Reports

An investigational gene therapy currently being developed by ASC Therapeutics, restored the levels of FVIII in a mouse model of hemophilia A and showed a favorable safety profile when tested in primates, suggesting it may also work in human patients, Hemophilia News Today reported last year in May.

Findings from these preclinical studies were presented by the company at the 22nd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in three presentations.

The experimental therapy uses the gene-editing tool CRISPR-Cas9 to insert a functional copy of F8 into liver cells that then produce FVIII, which is missing in people with hemophilia A.

Next steps in the research process include testing the therapy in humanized mice models of hemophilia A, which better mimic features of the human disease. Investigators also plan to perform additional experiments to evaluate the therapy’s effectiveness.

No. 3 – “First Hemophilia B Patient Treated with SB-FIX Gene Therapy in Phase 1/2 Trial

In January 2019, the first patient with severe hemophilia B was dosed in a Phase 1/2 trial (NCT02695160) investigating the safety, tolerability, and preliminary effectiveness of SB-FIX, Hemophilia News Today reported. The investigational genome-editing therapy was developed by Sangamo.

SB-FIX uses a combination of engineered zinc finger nucleases (ZFNs) — the most abundant DNA binding proteins in the body, which act as “molecular scissors” — and viral vectors to deliver a functional copy of the F9 gene to liver cells. That then produces the clotting factor IX (FIX) patients with hemophilia B are missing. The therapy had previously received both orphan drug and fast track designations from the FDA.

No. 2 – “BIVV001 Increases Half-life of Factor VIII in People with Severe Hemophilia A, Phase 1/2a Trial Shows

A single dose of BIVV001, an investigational FVIII replacement therapy developed by Bioverativ, increased the levels of FVIII in the blood of people with severe hemophilia A for a week without causing any undesirable side effects, according to early data from a Phase 1/2 trial (NTC03205163) called EXTEN-A.

The therapy also was found to increase the half-life of FVIII in the blood to 44 hours when administered at a dose of 65 IU/kg. The half-life of a drug refers to the period of time it takes for the levels of the compound to drop to half; higher values indicate that a drug lasts longer in the body after being administered.

BIVV001 is an experimental therapy that seeks to prolong the presence of FVIII in the patients’ blood to improve blood clotting and prevent spontaneous bleeding episodes when administered prophylactically . The therapy had previously received the designation of orphan drug from the FDA.

Bioverativ has since been acquired by Sanofi.

No. 1 – “Spark Therapeutics Provides Update on SPK-8011, Other Potential Gene Therapies for Hemophilia

SPK-8011, an investigational gene therapy currently being developed by Spark Therapeutics, was found to safely reduce the frequency of annual bleeding episodes by 97% in patients with severe or moderately severe hemophilia A with just a single dose, results of a Phase 1/2 trial (NCT03003533) sponsored by the company showed.

These preliminary findings included data from the first 12 patients dosed in the study. The trial is still recruiting participants from several sites across the U.S., Canada, and Australia.

Spark also has launched an observational study (NCT03432520) that will follow patients who participated in this Phase 1/2 trial for an extended period of time, so as to assess the long-term safety and efficacy of the therapy.

In addition to SPK-8011, the company also is developing SPK-8016, another form of gene therapy specifically for those with hemophilia A with FVIII inhibitors. A Phase 1/2 trial (NCT03734588) testing the safety, tolerability, and efficacy of SPK-8016 in men with severe hemophilia A is currently underway and recruiting participants. For more information on enrollment, visit here.

Hemophilia News Today hopes these stories and our reporting throughout 2020 contribute to informing and improving the lives of those with hemophilia and their loved ones.

We wish all our readers a happy 2020.