Update: On Aug. 20, Audentes announced that a third patient in the AT132 clinical trial has died.
Gene therapy has emerged rapidly in recent years because the field overcame safety concerns most notably, the tragic death of teenager Jesse Gelsinger in a clinical trial in 1999 that cooled initial optimism and slowed research.
Newer methods to deliver genetic medicine have been proven out in clinical testing and two therapies are now approved in the U.S., both for rare inherited diseases. Others, for diseases like hemophilia and Duchenne muscular dystrophy, could soon follow.
So far, this current wave of therapies have generally appeared safe. Encouraged, developers have tested higher and higher doses of gene therapies, aiming to expand their potential effectiveness. Higher doses are particularly important for neuromuscular diseases, since the treatment must travel through the bloodstream to reach the right tissue.
Two years ago, gene therapy pioneer Jim Wilson who led the Gelsinger trial at the University of Pennsylvania two decades ago expressed concern about the strategy, fearing that pushing doses too high might lead to safety problems. Wilson and UPenn colleagues published a paper in the journal Human Gene Therapy noting liver and nerve damage in animal experiments with a certain type of gene therapy, and called for researchers to do more monitoring.
While other gene therapy studies have been stopped in recent years, the deaths observed in Audentes' trial are particularly worrisome.
Audentes' therapy has shown promise in early tests, enough for Astellas to pay $3 billion for the company in December. The pivotal study of AT132 began in 2017 and Audentes aimed to submit an application with the Food and Drug Administration this year.
According to a letter Audentes sent to patient groups, however, that will no longer happen.
On May 6, Audentes told the groups that a patient treated with a high dose of AT132 had died from sepsis. Two others also given the high dose had then experienced serious side effects.
Six weeks later, on June 23, Audentes CEO Natalie Holles and chief medical officer Edward Conner sent a second letter explaining that one of those two had also died. That patient experienced progressive liver dysfunction, which didn't respond to standard treatment. His condition worsened and he ultimately died from a bacterial infection and sepsis.
"There have been some incredible outcome measures with some of the children but the science needs to continue to evolve," said Alison Rockett Frase, president of the Joshua Frase Foundation, one of the patient groups Audentes wrote. "Our community is devastated by the loss of these two children," she added in an interview.
On Aug. 20,Audentes reported that a third patient, also treated with a high dose of the gene therapy,had died from gastrointestinal bleeding.
Audentes is still collecting information, monitoring all of the study's other patients and is in touch with regulators. A total of 17 patients have been treated with the high dose of AT132 300 trillion vector genomes per kilogram of body weight.
"We are taking all necessary steps to understand these events and incorporate what we learn into our development plan going forward," Holles and Conner wrote in their letter. "We are currently assessing the impact on potential regulatory filing timelines, however we will not be filing in mid-2020 as previously communicated."
They added, however, that none of these issues have been seen in the six patients treated with a lower dose, and all of those patients are "years out from treatment." Four of those patients had a history of liver or biliary system problems.
All three of the patients who died also had evidence of pre-existing liver problems and showed signs of liver dysfunction within a month of treatment with AT132, Audentes said.All three patients with liver problems were of older age and heavier weight.
None of those treated with a high dose currently have the type of liver dysfunction seen in the patients who died, Audentes said.
Audentes uses a type of adeno-associated virus, called AAV8, to deliver its gene therapy. Other companies, including Ultragenyx, RegenxBio and Biogen are developing gene therapies that also rely on AAV8.
The high dose Audentes uses is among the largest being tested in gene therapy.
Ned Pagliarulo contributed reporting.
The rest is here:
Third patient dies in halted study of Audentes gene therapy
- New gene therapy for sickle cell disease has been a long time coming, but is it a complete game-changer? - UCLA Health Connect - December 29th, 2023
- Sickle Cell Gene Therapy Reimbursement: Will Experience Matter? And Which Kind? - Pink Sheet - December 29th, 2023
- Cell and gene therapy will be top industry trend for pharma in 2024 - The Financial Express - December 29th, 2023
- Excision Bio Seeks to Suppress HIV Replication With CRISPR Gene Therapy - AJMC.com Managed Markets Network - December 29th, 2023
- Global Cell and Gene Therapy Manufacturing Industry is projected to surpass a valuation of US$ 240 B - PharmiWeb.com - December 29th, 2023
- Penn's gene therapy layoffs are the latest in biotech belt-tightening in Philly and beyond - The Philadelphia Inquirer - December 29th, 2023
- Adeno-associated Virus Gene Therapy Market is Projected to Grow at a CAGR of 43.4% from 2023-2033 - EIN News - December 29th, 2023
- How Does Gene Therapy Work? Types, Uses, Safety - Healthline - May 9th, 2023
- Gene therapy: Comprehensive overview and therapeutic applications - April 7th, 2023
- Thanks to collaboration between Stand Up Therapeutics and VectorBuilder, a paraplegic patient will get gene therapy for the first time - Business... - January 21st, 2023
- Gene editing | Definition, History, & CRISPR-Cas9 | Britannica - January 4th, 2023
- A short history of gene therapy - Boston Children's Answers - December 27th, 2022
- Gene Therapy Analytical Development Summit 2022 | Home - December 27th, 2022
- $3.5-Million Hemophilia Gene Therapy Is World's Most Expensive Drug - Scientific American - December 10th, 2022
- CAR T Global Consultant Inc. Announce their Collaboration with Titronbio - a company founded in Shanghai China by a renowned leader in the field of... - December 10th, 2022
- Cell and Gene Therapy Manufacturing Services Market Size In 2023 | Financial Performance, In-Depth Insight of Trends, Key Players (Thermo Fisher... - December 10th, 2022
- How Gene Therapy Can Cure or Treat Diseases | FDA - December 2nd, 2022
- FDA Approves First Gene Therapy to Treat Adults with Hemophilia B - FDA.gov - November 24th, 2022
- Fact Check-mRNA vaccines are distinct from gene therapy ... - Reuters - October 29th, 2022
- Gene therapy: The Potential for Treating Type 1 Diabetes - Healthline - October 13th, 2022
- The promised land of gene therapy: Commercialization of novel gene-editing technology in beta-thalassemia - PMLiVE - October 13th, 2022
- Gene Therapy Hits Its Stride in the Clinic - Genetic Engineering & Biotechnology News - October 13th, 2022
- FDA Expands Oversight of Cell and Gene Therapies - Pharmaceutical Technology Magazine - October 13th, 2022
- Rocket Pharmaceuticals Announces Presentations Highlighting Lentiviral Gene Therapies at the 29th Annual Congress of the European Society of Gene... - October 13th, 2022
- Health Alert for Parents: How one boy is thriving following treatment with a gene therapy after receiving an early diagnosis - PR Newswire - October 13th, 2022
- M6P Therapeutics Presents Novel AAV Gene Therapy Approach for the Treatment of Gaucher Disease at the ESGCT 29th Annual Congress - Business Wire - October 13th, 2022
- Two Cell and Gene Therapies Manufactured at Lonza Houston Reach FDA Approval - Contract Pharma - October 13th, 2022
- Ascidian starts up with $50M and a twist on RNA editing - BioPharma Dive - October 13th, 2022
- Viral Vector Manufacturing, Non-Viral Vector Manufacturing and Gene Therapy Manufacturing Market Report 2022 - ResearchAndMarkets.com - Business Wire - October 13th, 2022
- Exopharm identifies two new lead programs as exosomes gain prominence in gene therapy - Stockhead - October 13th, 2022
- What Do We Know About Gene Therapy and Cystic Fibrosis? - The Epoch Times - October 13th, 2022
- CSafe and BioLife Solutions, Inc. announce partnership to expand supply chain solutions for the cell and gene therapy market - PR Newswire APAC - PR... - October 13th, 2022
- Genomics in Cancer Care Market is estimated to be US$ 72.61 billion by 2032 with a CAGR of 16.3% during the forecast period 2032 - By PMI -... - October 13th, 2022
- After $100M deal, J&J links gene therapy to improved vision in early-phase trial - FierceBiotech - October 4th, 2022
- Bayer Head Admits COVID-19 Vaccine is Gene Therapy - October 4th, 2022
- New Gene Therapy Shows Promise for Treating Age Related Macular ... - October 4th, 2022
- BioMarin resubmits its hemophilia gene therapy to the FDA - BioPharma Dive - October 4th, 2022
- Why Philly ranks #2 among best cell and gene therapy hubs in the US - Technical.ly - October 4th, 2022
- AMPLIFYBIO ACQUIRES PACT PHARMA ASSETS TO ENHANCE CELL AND GENE THERAPY CHARACTERIZATION CAPABILITIES - PR Newswire - October 4th, 2022
- bluebird's (BLUE) Gene Therapy Approvals to Drive the Top Line - Zacks Investment Research - October 4th, 2022
- Researchers Develop Potential Gene Therapy to Treat Blindness - Managed Healthcare Executive - October 4th, 2022
- Voyager Therapeutics Announces Data Presentations at the 29th Annual Congress of the European Society of Gene & Cell Therapy - GlobeNewswire - October 4th, 2022
- Viral Vector Manufacturing, Non-Viral Vector Manufacturing and Gene Therapy Manufacturing Market by Scale of Operation, Type of Vector, Application... - October 4th, 2022
- Sanofi partners with Scribe to gain gene editing tools for cell therapy work - BioPharma Dive - October 4th, 2022
- Real Endpoints Marketplace announces collaboration with bluebird bio to help scale delivery of a first-of-its-kind value-based contract for one-time... - October 4th, 2022
- Vertex given green light to seek US approval of CRISPR-based therapy - BioPharma Dive - October 4th, 2022
- Atsena Therapeutics Announces Positive Results from Phase I/II Clinical Trial of ATSN-101 for the Treatment of GUCY2D-associated Leber Congenital... - October 4th, 2022
- Meet with the OrganaBio executives in-person at The Cell & Gene Meeting on the Mesa - Business Wire - October 4th, 2022
- Ocular Gene Therapy: A Literature Review With Focus on Current Clinical Trials - Cureus - September 25th, 2022
- Will experience support use of first-ever retinal gene therapy? - Ophthalmology Times - September 25th, 2022
- Rejuvenate Bio CEO highlights ambitious approach of using gene therapy to reverse aging - MedCity News - September 25th, 2022
- Gene therapy R&D market is projected to grow at a CAGR of 30.1% by 2032: Visiongain Reports Ltd - GlobeNewswire - September 25th, 2022
- Emulate Announces New Gene Therapy Application Enabling Accelerated Development of Treatments for Genetic Diseases with Organ-on-a-Chip Technology -... - September 25th, 2022
- CSL flexes gene therapy muscle with latest drug - Sydney Morning Herald - September 25th, 2022
- FDA Updates for the Week of Sept. 19, 2022 - Managed Healthcare Executive - September 25th, 2022
- AVROBIO Receives Rare Pediatric Disease Designation From FDA For First Gene Therapy In Development For Cy - Benzinga - September 25th, 2022
- Preparing Europe for a new generation of innovative therapies - Open Access Government - September 25th, 2022
- KSQ Therapeutics Announces Leadership and Board Additions - Business Wire - September 25th, 2022
- Hemophilia gene therapies from BioMarin, CSL pick up an early ICER endorsement - FiercePharma - September 16th, 2022
- Challenges In Gene Therapy - University of Utah - September 16th, 2022
- Hopkinton bioscience company forms advisory board for cell and gene therapy - Worcester Business Journal - September 16th, 2022
- Gene Therapy Restores Some Vision in Colorblind Children - Pharmacy Times - September 16th, 2022
- Coave Therapeutics partners with IMN on gene therapy - Labiotech.eu - September 16th, 2022
- MeiraGTx's Industry-Leading Gene Therapy Manufacturing Facility in Shannon, Ireland Formally Introduced by Head of Irish Government -... - September 16th, 2022
- Bluebird CFO resigns ahead of gene therapy launch - BioPharma Dive - September 16th, 2022
- Enrollment completed in STARLIGHT Phase 2 clinical trial of MCO-010 optogenetic gene therapy for Stargardt disease - Ophthalmology Times - September 16th, 2022
- Global Cancer Gene Therapy Market to Reach $11.35 Billion by 2030 at a CAGR of 23.3% - PR Newswire - September 16th, 2022
- How WhiteLab Genomics is using AI to aid gene and cell therapy development - TechCrunch - September 16th, 2022
- CAR-T Cell Therapy Market Segmentation and Forecast Analysis up to 2027 - BioSpace - September 16th, 2022
- Cluster-busters against Cancer and a Potential New Gene Therapy for LCA - BioSpace - September 16th, 2022
- Ori Biotech and CTMC team up on cell therapy delivery - BioPharma-Reporter.com - September 16th, 2022
- Adverum (ADVM) Doses First Patient in the Mid-Stage wAMD Study - Zacks Investment Research - September 16th, 2022
- Engensis Gene Therapy for ALS Found Safe in Small Phase 2a Trial |... - ALS News Today - September 8th, 2022
- A new gene therapy based on antibody cells is about to be tested in humans - MIT Technology Review - September 8th, 2022
- Myrtelles rAAV-Olig001-ASPA Gene Therapy Candidate for Canavan Disease Receives Advanced Therapy Medicinal Product Classification from the European... - September 8th, 2022
- Sangamo presses ahead with Fabry disease gene therapy - BioPharma Dive - September 8th, 2022
- The gene therapy that could transform the lives of millions - ABC News - September 8th, 2022
- As Philly becomes a hub for life sciences, a new program will train workers for jobs in the field - The Philadelphia Inquirer - September 8th, 2022
- Mayflower BioVentures to Announce New Cell & Gene Therapy Companies within Months - BioSpace - September 8th, 2022
- Carroucell Raises 1.5 Million to Introduce Breakthrough Microcarriers and Customizable Processes to Cell and Gene Therapy Market - Business Wire - September 8th, 2022