Study results from an open-label, single-dose, multi-center, multinational phase III trial, presented during the late-breaking abstract session of the all-virtual 62nd American Society of Hematology (ASH) Annual Meetings show that etranacogene dezaparvovec (previously known was AAV5-hFIXco-Padua; AMT-061; uniQure/CSL Behring), an investigational gene therapy for hemophilia B, is safe and effective.
The two most common types of hemophilia are hemophilia A, in which patients is lack of clotting Factor VIII, and hemophilia B, caused by a lack of the ability to produce the blood clotting factor IX as the result of an inherited mutation of the gene for factor IX.
Both types of hemophilia can lead to spontaneous and uncontrolled bleeding into muscles, organs, and joints as well as prolonged bleeding following injuries or surgery, which leads to joint deterioration and chronic pain.
Hemophilia B, which accounts for about one-fifth of hemophilia cases.
Clinical trialThe study of etranacogene dezaparvovec recruited adult male patients with severe or moderate-severe hemophilia B.
The results of the study demonstrated that a single administration of the gene therapy etranacogene dezaparvovec led to sustained increases of Factor IX to functionally curative levels capable of eliminating the need for regular infusions to control and prevent bleeding episodes. As a result, most patients were able to stop intensive intravenous regimens. The studys authors believe that the results may open doors for patients previously not included in gene therapy trials.
Blood clotting proteinIn the trial included 52 patients and is the largest and most inclusive hemophilia B gene therapy trial to date. The trial is also the first to include patients with certain immune system markers and found that they did not appear to confer any increased risks, a finding that could significantly broaden the number of patients who may be eligible for gene therapy.
A majority of trial participants (96%) successfully discontinued factor IX replacement therapy after receiving the gene therapy and have been producing their own factor IX for six months. The findings suggest gene therapy could, with a single treatment, give patients the ability to maintain Factor IX levels and reduce or eliminate the need for additional factor IX replacement therapy, according to researchers.
Most patients with hemophilia B are bound to a prophylactic factor regimen of one to two intravenous infusions per week from birth through the rest of their life, said senior study author Steven W. Pipe, M.D., of the University of Michigan, Ann Arbor, Michigan, who presented the result of the study during the Late-Breaking Abstracts session on Tuesday, December 8 at 7:00 a.m. Pacific time.
Gene therapy offers the chance to liberate patients from the burden of their prior treatments, allowing for spontaneity and the freedom to do more in day-to-day life, Pipe added.
Replacement therapyFactor IX replacement therapy can reduce bleeding associated with hemophilia B, but it requires weekly or biweekly infusions to maintain factor IX levels, a burdensome regimen that costs several hundred thousand dollars per year.
In gene therapy, viral particles are used to shuttle engineered genes to cells in the liver. These genes replace the patients faulty factor IX gene, allowing the patients own body to produce factor IX on an ongoing basis. While several gene therapies for hemophilia have shown promise in early phase trials, the study is the first phase III trial to test the approach in a large and diverse array of patients, Pipe said.
Fifty-four patients enrolled in the study; all were dependent on factor IX replacement therapy, and 70% had bleeding episodes in the six months prior to the study despite this prophylactic treatment.
After receiving the etranacogene dezaparvovec gene therapy via a single infusion lasting roughly one hour, factor IX activity increased rapidly from a baseline of up to 2% (moderate to severe hemophilia) to a mean of 37% (very mild hemophilia) at 26 weeks, meeting the trials primary endpoint.
At that level, a patients bleeding risk is essentially the same as someone without hemophilia, Pipe noted.
Seventy-two percent of patients reported no bleeding events in the 26 weeks after receiving the gene therapy.
This tells us that the bleeding phenotype can be corrected through this treatment, which is a remarkable achievement, Pipe said.
Fifteen patients experienced some bleeding, which the researchers indicate is not unexpected given that many of the patients had severely affected joints entering the trial.
What weve seen from patients in the study is that they really dont have to think about their hemophilia anymore. The transformative nature that we hear from the patient stories is, to me, the most important outcome from this study, Pipe said.
Neutralizing antibodiesThe trial is also the first to attempt gene therapy in patients with neutralizing antibodies, a component of the immune system that helps the body fight pathogens. About 40% of trial participants had antibodies to adeno-associated virus serotype 5, or AAV5*, the viral vector used in etranacogene dezaparvovec.
In any other trial protocol, these patients would not have been eligible to participate, Pipe noted.
Previous trials have excluded such patients from gene therapies that use viral vectors under the assumption that antibodies could either block the uptake of the viral vectors in the liver or trigger a dangerous immune response to the therapy. The trial found no evidence of either problem, suggesting neutralizing antibodies do not preclude successful gene therapy.
Two patients did not respond to gene therapy. One did not receive a full dose because the infusion was stopped after the patient showed signs of a reaction to the infusion. The other had a level of neutralizing antibodies about five times higher than any other patient. Since other patients with neutralizing antibodies responded well to the therapy regardless of their level of antibodies, this finding suggests antibodies may pose a problem only at extremely high levels.
No treatment-related serious adverse events were reported. Adverse events were relatively common, occurring in 68% of patients, but most were mild and related to the infusion itself. Nine patients showed evidence of an immune response to the therapy, which was resolved in all cases with a course of corticosteroids.
The researchers will continue to follow patients for five years. Patients will be assessed for sustained factor IX production and effective bleed control over 52 weeks, as well as patient-reported outcome measures to assess the impact on health-related Quality of Life (hrQoL).
Note* Adeno-associated virus serotype 5- (AAV5-) based gene therapies have been demonstrated to be safe and well-tolerated in a multitude of clinical trials. Etranacogene dezaparvovec consists of an AAV5 viral vector carrying a gene cassette with the patent-protected Padua variant of Factor IX (FIX-Padua). The investigational agent has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration and access to the Priority Medicines (PRIME) regulatory initiative by the European Medicines Agency.
Clinical trialsHOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients NCT03569891
Reference[1] Pipe SW, Recht M, Key NS, Leebeek FWG, Castaman G, Lattimore SU, Van der Valk P, Peerlinck K, et al. LBA-6 First Data from the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults with Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies [Abstract LBA-6]
Original post:
ASH 2020: Novel Gene Therapy Found to be Safe and Effective in Treatment of Hemophilia B - OncoZine
- 001 Faulty Circuits (preview) [Last Updated On: April 7th, 2010] [Originally Added On: April 7th, 2010]
- 002 Faulty Circuits (preview) [Last Updated On: April 7th, 2010] [Originally Added On: April 7th, 2010]
- 003 Rare flowers and common herbal supplements get unmasked with plant DNA barcoding [Last Updated On: April 20th, 2010] [Originally Added On: April 20th, 2010]
- 004 Rare flowers and common herbal supplements get unmasked with plant DNA barcoding [Last Updated On: April 20th, 2010] [Originally Added On: April 20th, 2010]
- 005 Biomarker Studies Could Realize Goal of More Effective and Personalized Cancer Medicine [Last Updated On: April 27th, 2010] [Originally Added On: April 27th, 2010]
- 006 Biomarker Studies Could Realize Goal of More Effective and Personalized Cancer Medicine [Last Updated On: April 27th, 2010] [Originally Added On: April 27th, 2010]
- 007 Schizophrenia shares genetic links with autism, genome study shows [Last Updated On: May 12th, 2010] [Originally Added On: May 12th, 2010]
- 008 Schizophrenia shares genetic links with autism, genome study shows [Last Updated On: May 12th, 2010] [Originally Added On: May 12th, 2010]
- 009 Alzheimer's: Forestalling the Darkness with New Approaches (preview) [Last Updated On: May 28th, 2010] [Originally Added On: May 28th, 2010]
- 010 Alzheimer's: Forestalling the Darkness with New Approaches (preview) [Last Updated On: May 28th, 2010] [Originally Added On: May 28th, 2010]
- 011 Large-Scale Autism Study Reveals Disorder's Genetic Complexity [Last Updated On: June 12th, 2010] [Originally Added On: June 12th, 2010]
- 012 Large-Scale Autism Study Reveals Disorder's Genetic Complexity [Last Updated On: June 12th, 2010] [Originally Added On: June 12th, 2010]
- 013 Cancer Therapy Goes Viral: Progress Is Made Tackling Tumors with Viruses [Last Updated On: June 24th, 2010] [Originally Added On: June 24th, 2010]
- 014 Cancer Therapy Goes Viral: Progress Is Made Tackling Tumors with Viruses [Last Updated On: June 24th, 2010] [Originally Added On: June 24th, 2010]
- 015 Vaccines Derived from Patients' Tumor Cells Are Individualizing Cancer Treatment [Last Updated On: June 26th, 2010] [Originally Added On: June 26th, 2010]
- 016 Vaccines Derived from Patients' Tumor Cells Are Individualizing Cancer Treatment [Last Updated On: June 26th, 2010] [Originally Added On: June 26th, 2010]
- 017 A genome story: 10th anniversary commentary by Francis Collins [Last Updated On: June 29th, 2010] [Originally Added On: June 29th, 2010]
- 018 A genome story: 10th anniversary commentary by Francis Collins [Last Updated On: June 29th, 2010] [Originally Added On: June 29th, 2010]
- 019 Hair Trigger: How a Cell's Primary Cilium Functions as a Molecular Antenna [Last Updated On: June 30th, 2010] [Originally Added On: June 30th, 2010]
- 020 Hair Trigger: How a Cell's Primary Cilium Functions as a Molecular Antenna [Last Updated On: June 30th, 2010] [Originally Added On: June 30th, 2010]
- 021 DNA Drugs Come of Age (preview) [Last Updated On: July 16th, 2010] [Originally Added On: July 16th, 2010]
- 022 DNA Drugs Come of Age (preview) [Last Updated On: July 16th, 2010] [Originally Added On: July 16th, 2010]
- 023 2 Genes Linked to Embryonic Brain Impairment in Down's Syndrome [Last Updated On: July 22nd, 2010] [Originally Added On: July 22nd, 2010]
- 024 2 Genes Linked to Embryonic Brain Impairment in Down's Syndrome [Last Updated On: July 22nd, 2010] [Originally Added On: July 22nd, 2010]
- 025 Stem Cells from Reprogrammed Adult Cells Found to Bring Along Genetic Defects of Their Donors [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- 026 Was Darwin a Punk? A Q&A with Punker-Paleontologist Greg Graffin [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- 027 Parkinsonian Power Failure: Neuron Degeneration May Be Caused by a Cellular Energy System Breakdown [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- 028 Stem Cells from Reprogrammed Adult Cells Found to Bring Along Genetic Defects of Their Donors [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- 029 Was Darwin a Punk? A Q&A with Punker-Paleontologist Greg Graffin [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- 030 Parkinsonian Power Failure: Neuron Degeneration May Be Caused by a Cellular Energy System Breakdown [Last Updated On: October 11th, 2010] [Originally Added On: October 11th, 2010]
- 031 Desperation Drives Parents to Dubious Autism Treatments (preview) [Last Updated On: October 13th, 2010] [Originally Added On: October 13th, 2010]
- 032 Desperation Drives Parents to Dubious Autism Treatments (preview) [Last Updated On: October 17th, 2010] [Originally Added On: October 17th, 2010]
- 033 Revolution Postponed: Why the Human Genome Project Has Been Disappointing (preview) [Last Updated On: October 21st, 2010] [Originally Added On: October 21st, 2010]
- 034 Controlling the Brain with Light (preview) [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 035 Optogenetics: Controlling the Brain with Light [Extended Version] [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 036 Clear New Insights into the Genetics of Depression [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 037 TEDMED 2010: Technology and the people [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 038 Bacteria, the anti-cancer soldier [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 039 Revolution Postponed: Why the Human Genome Project Has Been Disappointing (preview) [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 040 Controlling the Brain with Light (preview) [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 041 Optogenetics: Controlling the Brain with Light [Extended Version] [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 042 Clear New Insights into the Genetics of Depression [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 043 TEDMED 2010: Technology and the people [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 044 Bacteria, the anti-cancer soldier [Last Updated On: November 7th, 2010] [Originally Added On: November 7th, 2010]
- 045 Scientific regress: When science goes backward [Last Updated On: November 29th, 2010] [Originally Added On: November 29th, 2010]
- 046 Can You Live Forever? Maybe Not--But You Can Have Fun Trying [Last Updated On: January 1st, 2011] [Originally Added On: January 1st, 2011]
- 047 How to Fix the Obesity Crisis (preview) [Last Updated On: January 22nd, 2011] [Originally Added On: January 22nd, 2011]
- 048 Scientific regress: When science goes backward [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- 049 Can You Live Forever? Maybe Not--But You Can Have Fun Trying [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- 050 How to Fix the Obesity Crisis (preview) [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- 051 Personalizing cancer medicine [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- 052 New Salmonella strain delivers gene-based therapy to fight virus in mice [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- 053 Personalizing cancer medicine [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- 054 New Salmonella strain delivers gene-based therapy to fight virus in mice [Last Updated On: February 14th, 2011] [Originally Added On: February 14th, 2011]
- 055 Steps toward a Bionic Eye [Last Updated On: February 18th, 2011] [Originally Added On: February 18th, 2011]
- 056 Steps toward a Bionic Eye [Last Updated On: February 20th, 2011] [Originally Added On: February 20th, 2011]
- 057 Giving HIV a Poor Reception: New AIDS Treatment Tinkers with Immune Cell Genes [Last Updated On: March 6th, 2011] [Originally Added On: March 6th, 2011]
- 058 Giving HIV a Poor Reception: New AIDS Treatment Tinkers with Immune Cell Genes [Last Updated On: March 6th, 2011] [Originally Added On: March 6th, 2011]
- 059 Smaller, cheaper, faster: Does Moore's law apply to solar cells? [Last Updated On: March 27th, 2011] [Originally Added On: March 27th, 2011]
- 060 Smaller, cheaper, faster: Does Moore's law apply to solar cells? [Last Updated On: March 27th, 2011] [Originally Added On: March 27th, 2011]
- 061 New Drugs for Hepatitis C on the Horizon [Last Updated On: April 10th, 2011] [Originally Added On: April 10th, 2011]
- 062 Can we capture all of the world's carbon emissions? [Last Updated On: April 10th, 2011] [Originally Added On: April 10th, 2011]
- 063 New Drugs for Hepatitis C on the Horizon [Last Updated On: April 10th, 2011] [Originally Added On: April 10th, 2011]
- 064 Can we capture all of the world's carbon emissions? [Last Updated On: April 10th, 2011] [Originally Added On: April 10th, 2011]
- 065 Drug-resistant genes found in cholera and dysentery strains in New Delhi water supply [Last Updated On: May 1st, 2011] [Originally Added On: May 1st, 2011]
- 066 Fast Track to Vaccines: How Systems Biology Speeds Drug Development (preview) [Last Updated On: May 1st, 2011] [Originally Added On: May 1st, 2011]
- 067 Drug-resistant genes found in cholera and dysentery strains in New Delhi water supply [Last Updated On: May 1st, 2011] [Originally Added On: May 1st, 2011]
- 068 Fast Track to Vaccines: How Systems Biology Speeds Drug Development (preview) [Last Updated On: May 1st, 2011] [Originally Added On: May 1st, 2011]
- 069 Autism's Tangled Genetics Full of Rare and Varied Mutations [Last Updated On: June 19th, 2011] [Originally Added On: June 19th, 2011]
- 070 A New Look at Obsessive-Compulsive Disorder (preview) [Last Updated On: June 19th, 2011] [Originally Added On: June 19th, 2011]
- 071 Autism's Tangled Genetics Full of Rare and Varied Mutations [Last Updated On: June 19th, 2011] [Originally Added On: June 19th, 2011]
- 072 A New Look at Obsessive-Compulsive Disorder (preview) [Last Updated On: June 19th, 2011] [Originally Added On: June 19th, 2011]
- 073 Close Encounters of Science and Medicine [Last Updated On: July 3rd, 2011] [Originally Added On: July 3rd, 2011]
- 074 Close Encounters of Science and Medicine [Last Updated On: July 3rd, 2011] [Originally Added On: July 3rd, 2011]
- 075 New Report Details Uphill Battle to Solve the U.S.'s Pain Problem [Last Updated On: July 24th, 2011] [Originally Added On: July 24th, 2011]
- 076 New Report Details Uphill Battle to Solve the U.S.'s Pain Problem [Last Updated On: July 24th, 2011] [Originally Added On: July 24th, 2011]
- 077 A Breath of Fresh Air: New Hope for Cystic Fibrosis Treatment (preview) [Last Updated On: August 7th, 2011] [Originally Added On: August 7th, 2011]
- 078 A Breath of Fresh Air: New Hope for Cystic Fibrosis Treatment (preview) [Last Updated On: August 7th, 2011] [Originally Added On: August 7th, 2011]
- 079 Gene therapy improves stem cell transplantation - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- 080 THE NEW MORGELLONS HAIR - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]