The phase 12 trials threeyear data were reported in a study, multiyear followup of aav5hfviiisq gene therapy for hemophilia a, recently published in the new england journal of medicine. Investigational gene therapy for hemophilia is designed to add a functional copy of the factor viii or factor ix gene to the cells command center nucleus. Hemophilia a, an xlinked bleeding disorder, results from mutations in the gene encoding coagulation factor viii. Gene therapy helps patients with hemophilia national. Quick take gene therapy in patients with severe hemophilia a 02. Novo nordisk has entered into a collaboration agreement with bluebird bio to develop new therapies based on gene editing for a series of genetic disorders, including hemophilia the companies have agreed to work together on a threeyear research project that will focus on the identification and development of gene therapy candidates to treat hemophilia a, a type of hemophilia caused by the. Hemophilia a is a genetic disease caused by the deficiency of clotting factor viii. Dextran antibodies, complement conversion and circulating immune complexes after intravenous iron dextran therapy in dialysed patients. Nov 01, 2014 the author holds pending and issued patents in the area of gene therapy for hemophilia. Intern clinical science hemophilia a gene therapy at. The gene therapy for hemophilia module is an adaptation of the global national member organization nmo training 2018 plenary presentation by glenn pierce, wfh vice president, medical, and is part of the wfh treatment products elearning program designed for individual selfdirected or smallgroup learning. Aavbased gene therapy is one of a number of novel approaches for treatment of hemophilia with other gene therapy in vivo and ex vivo and nonreplacement therapies progressing through clinical trials.
The arguments in favor of gene therapy for hemophilia have. Submit one set of either electronic or written comments on this draft guidance by. Spark is also using gene therapy to treat a cause of inherited blindness, lebers congenital amaurosis, for which no treatment exists. This guidance provides recommendations on the clinical trial design.
The guidance document provides recommendations to stakeholders developing human gene therapy gt products for the treatment. Treating hemophilia with gene therapy medical xpress. Biomarin is seeking fda approval of valoctocogene roxaparvovec for the treatment of adults with hemophilia a. Wfh elearning platform gene therapy for hemophilia. Mazza, mesenchymal stem cell treatment for hemophilia. The author is an employee of and holds equity interest in spark therapeutics, which has an interest in developing gene therapy for hemophilia. Gene therapy trial for platelet derived factor viii production in hemophilia a the safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
Leap forward towards gene therapy cure for haemophilia a. Hemophilia affects nearly 200,000 individuals worldwide and an estimated 20,000 people in the united states. Treatment of hemophilia a and b national hemophilia foundation. Hemophilia b gene therapy candidate dtx101 pulled from. Gene therapy corrects factor viii levels in hemophilia a. Nathwani arrived from the university college london to work as a postdoctoral fellow in my lab july 1997.
Apr 11, 2020 this collection of programs provides important information on the science behind gene therapy for hemophilia, the latest safety and efficacy data from clinical trials, and the potential role for gene therapy in addressing the challenges of current treatment methods. Dec 12, 2017 researchers report first successful gene therapy for hemophilia a tuesday, december 12, 2017 in an ongoing phase iii study of patients with hemophilia a, those who received a single infusion of bmn 270 an adenoassociated virus serotype 5 aav5 vector containing the bdomaindeleted f8 gene had improved levels of factor viii fviii, with. The work in my laboratory dedicated to the development of gene therapy for hemophilia, based on gene transfer with recombinant adenoassociated virus raav, began after dr. Ix corrected the hemostatic defect in hemophilia b dogs in a dose dependent fashion. This guidance is intended to assist stakeholders developing human gene therapy gt 1 products for the treatment of hemophilia. Monahan, gene therapy in an era of emerging treatment options for hemophilia b, journal of thrombosis and haemostasis, 2015, s151wiley online library. After one dose of gene therapy, hemophilia b patients. Dec 06, 2017 the hemophilia study is small but very promising, and it gives me the sense that gene therapy for hemophilia b is going to be at our disposal in no time, maybe a few years from now, said. There are currently three companies that are in the process of developing their own gene therapy for this rare blood disorder. Our product candidate amt180 is a novel hemophilia a gene therapy that has the potential to treat all hemophilia a patients, including those with past and current inhibitors. Groundbreaking gene therapy trial set to cure hemophilia.
There are existing treatments for hemophilia that require lifelong administration, while gene therapy may offer a onetime treatment to address the cause of the disease. Human gene therapy for hemophilia draft guidance for industry this guidance document is for comment purposes only. Gene therapies for hemophilia hit the mark in clinical trials. The author holds pending and issued patents in the area of gene therapy for hemophilia. Evolution in hemophilia therapy by brenna raines, ppta senior manager, health policy sara stefanelli, ppta communications assistant, europe o ver the past 50 years, many technological changes have occurred within the hemophilia community that had a strong impact on patients and their care. Bill maurits and his family visiting niagara falls two month after his hemophilia was treated with gene therapy. Results from recent trials of this revolutionary approach have restored patients anticoagulant factor activity levels to normal or nearnormal levels and reduced patients annualized bleeding rates. Gene therapy shown to offer longterm benefits for people. Dec 09, 2017 coming just days after reports of a gene therapy that pushed the bleeding disorder hemophilia b into remission, new research suggests the same could be true for adults with the a form of the. When they infuse a gene for the correct bloodclotting factor, its taken up by the patient who then can produce it on their own. Factor viii and factor ix gene therapy have become a tangible possibility since phase i data recently have been published.
Hemophilia is an xlinked, recessively inherited coagulation disorder entailing a lack of coagulation factor viii, fviii hemophilia a or. Valoctocogene roxaparvovec bmn 270 for hemophilia a. From diagnosis to therapy giridhara rao jayandharan, ph. So they no longer have to inject clotting factor to avoid potentially crippling or fatal consequences. Impact of hemophilia home therapy program on a regional blood center. This constructive action by the fda marks the first marketing application accepted for a gene therapy gt product for any type of hemophilia in. Hemophilia is a genetic disease that prevents blood from clotting properly leading to prolonged internal and external bleeding. Results from this study represent a promising step toward making gene therapy a viable treatment option for hemophilia b. Through this type of treatment, patients with severe hemophilia could attain moderate hemophilia clotting levels, thus leading to an increased reduction in bleeding.
Valoctocogene roxaparvovec is gene therapy designed for the treatment of hemophilia a. Nathwani arrived from the university college london to work. The title of this talk is gene therapy for hemophilia. Obstacles and future of gene therapy for hemophilia. For preclinical research on gene therapy in hemophilia, several wellvalidated small and large hemophilic animal models are available. Protein replacement therapy and gene transfer in canine models. Different gene delivery methods are explored, focusing on those currently in clinical trials for gene therapy in hemophilia, and questions about how the body responds to these gene transfer techniques are explained. After one dose of gene therapy, hemophilia b patients maintain nearnormal levels of clotting factor. The potential price tag of the hemophilia b gene therapy is an issue, but george and porteus said it could be offset by eliminating the need for standard treatments. My name is katherine high, and im a professor of pediatrics at the university of pennsylvania school of medicine and an investigator of the howard hughes medical institute.
The clinical science team is comprised of medical and health professionals who are responsible for overseeing the safe and ethical conduct of studies in patients, and in this case, gene therapy for individuals with hemophilia a, an inherited bleeding disorder attributed to a deficiency or defect in a blood clotting protein called factor viii. Gene therapy effectively treats hemophilia b american. In this issue of blood, miesbach et al show that adenoassociated virus5 aav5 liverdirected gene therapy in severe and moderate hemophilia b was clinically effective, with patients achieving stable factor ix fix expression. Spark reports preliminary data from hemophilia a gene therapy.
Towards aav5mediated gene therapy for hemophilia a with. Hemophilia gene therapy is effective and safe blood. After many years, gene therapy in patients with hemophilia has started to show promising results in alleviating symptoms and improving the disease phenotype. Several strategies have been proposed for gene therapy for hemophilia. Storage time of blood products and transfusionrelated acute lung injury.
Towards aav5mediated gene therapy for hemophilia a with a factor ix variant that functions independently of fviii ying poi liu, phd uniqure biopharma b. For this reason, a survey among clinicians treating hemophilia b was. Another obstacle to aavmediated gene transfer for hemophilia a gene therapy is the size of the fviii coding sequence, which at 7. Dec 14, 2017 a cure for haemophilia is one step closer, following results published in the new england journal of medcine of a groundbreaking gene therapy trial led by the nhs in london. Researchers are aiming to repair the single gene mutation responsible for hemophilia by delivering a correct copy of the factorencoding gene. To improve the clinical phenotype of hemophilia, prolonged highlevel expression of clotting factors is needed. Hemophilia gene therapies have the potential to provide prolonged, highlevel expression of factor, and limit the need for frequent factor infusion. Aav5factor viii gene transfer in severe hemophilia a nejm.
Videos, documents, and other educational gene therapy resources. Hemophilia gene therapies focus of novo nordiskbluebird. The childrens hospital of philadelphia philadelphia, pa university of pittsburg pittsburg, pa. Submit one set of either electronic or written comments on. Spark reports preliminary data from hemophilia a gene therapy trial august 14, 2017 spark therapeutics, inc.
Identification of the profile of the patients with hemophilia b. Gene therapy for hemophilia is here and its working. Aug 15, 2016 the study, therapeutic approaches for treating hemophilia a using embryonic stem cells, published in hematologyoncology and stem cell therapy, shows that mice transplanted with these embryonic stem cells have therapeutic levels of human fviii. Human gene therapy for hemophila draft guidance for. While gene therapy has long been a topic of discussion within the hemophilia community, the idea of gene therapy as a treatment option is becoming a reality. Its not available yet, but after 20 years in development. Researchers report first successful gene therapy for hemophilia a. Coagulinb is avigens proprietary aav vector, which carries the gene for factor ix, the missing or deficient protein that causes hemophilia b.
Quick take gene therapy for factor ix deficiency 01. Several methods have been investigated to effectively and safely transmit genes that stimulate cells to release therapeutic factor viii fviii and factor ix fix into the circulation of people with hemophilia pwh. Advances and challenges for hemophilia gene therapy. Gene therapy for hemophilia is justified because it is a chronic disease and because a very regular factor infusion is required that may involve fatal risks and because it is very expensive. Gene therapy trial for platelet derived factor viii. According to a story from, the field of gene therapy has gained increasing relevance throughout 2019, and 2020 will likely be a continuation of this trend. Jun 11, 2016 bill maurits and his family visiting niagara falls two month after his hemophilia was treated with gene therapy.
Dec 11, 2017 scientists report they have successfully treated hemophilia b by giving sufferers gene therapy. Significant obstacles, however, need to be overcome prior to widespread adoption. Takeda demonstrates its longstanding commitment to. Future therapies while gene therapy has long been a topic of discussion within the hemophilia community, the idea of gene therapy as a treatment option is becoming a reality. While improved recombinant clotting factor products remain an important area of research, the quest for effective and safe gene therapy treatment for hemophilia continues concurrently. Gene therapy for hemophilia a and hemophilia b everyday. Gene therapy clinical trial for hemophilia b patients. Gene therapy may be longterm cure for type of hemophilia. An unequivocal sign of hemophilia is a bent leg, resulting. An area of gene therapy development that has gotten particularly hot recently is hemophilia a. For a long time gene therapy has been hailed as a potential cure for haemophilia, but the expectation has been that viable treatment is many years away in the future. These strategies are based on both in vivo and ex vivo approaches.
Gene therapy aims to achieve this by using two comple. Listing a study does not mean it has been evaluated by the u. While gene therapy holds great potential for the treatment of hemophilia. Gene therapy offers the potential for a cure for patients with hemophilia by establishing continuous endogenous expression of factor viii or factor ix fix following transfer of a functional gene to replace the hemophilic patients own defective gene. We believe that etranacogene dezaparvovec amt061 may be the first gene therapy to provide durable, curative benefits to nearly all patients with hemophilia b, with optimized clinical and safety benefits. The potential price tag of the hemophilia b gene therapy is an issue, but george and porteus. Hemophilia has long been one of the disorders thought most likely to be correctible with gene therapy, but previous approaches to deliver the gene have been disappointing, says nhlbi acting director dr. It is the most common type of hemophilia and occurs much more frequently in males. This collection of programs provides important information on the science behind gene therapy for hemophilia, the latest safety and efficacy data from clinical trials, and the potential.
Federal register human gene therapy for hemophilia. Adjunctive therapies are important, particularly where clotting factor concentrates are limited or not available, and may lessen the amount of treat ment product. Nhf is the leadinglargestonly national nonprofit organization dedicated to finding better treatments and cures for inheritable bleeding disorders and to preventing the complications of these disorders through education, advocacy and research. Dec 06, 2017 gene therapy may let hemophilia patients skip meds. Flowcytometry platform for intracellular detection of. One dose of a gene therapy given experimentally to patients by nhs doctors in the uk has allowed. If transferred successfully, the functional gene is intended to provide the correct instructions for the cell to make factor viii or factor ix clotting protein. The procedure was well tolerated and no immune responses were detected. Caring for your child with hemophilia national hemophilia. Ix corrected the hemostatic defect in hemophilia b dogs in a dosedependent fashion. Approximately 30 percent of patients with severe hemophilia a will develop an inhibitor that neutralizes the infused factor viii fviii activity.
The recent success of earlyphase clinical trials for adenoassociated viral aav liverdirected gene therapy for hemophilia b hb demonstrates the potential for gene therapy, in the future, to succeed proteinbased prophylaxis therapy for hb. Though the experience of a gene therapy for hb may provide a roadmap for how gene therapy for hemophilia a ha may navigate similar obstacles, there are important biological differences between fix and factor viii fviii that create their own set of unique barriers for gene therapy for ha. Researchers are also trying to develop a similar gene therapy for hemophilia a, which has proven more challenging. Dec 12, 2017 a small, earlystage study published in the new england journal of medicine found that a single intravenous infusion of a novel bioengineered gene therapy treatment freed nine of 10 hemophilia b. Nov 10, 2017 gene therapy for hemophilia has been in development for three decades and is now entering pivotalstage clinical trials.
Treatment for patients with hemophilia and other bleeding disorders has evolved over the past several decades. Gene therapy may allow hemophilia patients to go without meds. Bayer signs hemophilia gene therapy deal with avigen investors. Gene therapy for hemophilia is starting to come of age and promises to transform the way patients with this rare blood disease are treated.
Bone marrow iron and plasma ferritin in dialysed patients given intravenous irondextran. Two recent studies describe clinical successes for singledose gene therapy in trials for two forms of hemophilia. A breakthrough gene therapy treatment for haemophilia a has been shown to offer longterm benefits that have already transformed the lives of men in the uk. Biomarins gene therapy for hemophilia a submitted for u. Our goal in hemophilia b is to develop the safest and most effective gene therapy with the broadest application to patients. Takeda demonstrates its longstanding commitment to advancing.
Suzanne ocallaghan is hfa policy research and education manager. Hemophilia b gene therapy with a highspecificactivity. Human gene therapy for hemophila draft guidance for industry. Apr 01, 2015 hemophilia was a very interesting model for gene therapy as only a small increase of factor level can dramatically decrease the number of bleedings and prevent athropathy. Availability of these highcost novel therapeutics will require evolution of both clinical and financial healthcare services to allow equitable. Hemophilia b is an xlinked bleeding disorder that results from a deficiency or dysfunction of coagulation factor ix. While many different technology platforms exist for gene therapy, all current clinical trials for hemophilia employ adenoassociated vector aavbased cell transduction. Another gene therapy breakthrough against hemophilia. Gene therapy for hemophilia a and b could be a permanent cure for people who have these rare, sometimes lifethreatening conditions.
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