The gene therapy sector is currently thriving within the biotech industry, particularly since the first CRISPR-based therapy was approved to treat sickle cell disease and beta-thalassemia towards the end of 2023. And, with gene therapy now inevitably poised to deliver a wave of new treatments that have the potential to cure both rare and common diseases, there are numerous gene therapy companies operating within the sector.
In this article, we have listed 10 companies hoping to develop their own novel gene therapy candidates.
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Adverum Biotechnologies
Adverum Biotechnologies aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases by developing functional cures to restore vision and prevent blindness. To achieve this goal, the company leverages the research capabilities of its proprietary intravitreal (IVT) platform, developing durable, single-administration therapies that are designed to be delivered in physicians’ offices, which could ultimately eliminate the need for frequent ocular injections to treat these types of diseases.
Ixoberogene soroparvovec (Ixo-vec) is Adverum’s clinical-stage gene therapy product candidate being developed for the treatment of wet age-related macular degeneration (AMD). The current standard of care for wet AMD requires frequent injections in the eye and is a lifelong burden for many patients. Adverum wants to reduce this burden with Ixo-vec, which is designed to be administered as a one-time IVT injection in the physician’s office. The therapy recently showed positive preliminary efficacy and safety data in a phase 2 study, whereby both dose levels demonstrated potential best-in-class clinical activity in hard-to-treat patients, including treatment burden reduction and maintenance of both visual acuity and anatomic endpoints.
On February 5, Adverum announced a $127.5 million private placement financing. The proceeds from this (combined with current cash, cash equivalents, and marketable securities) are expected to fund the gene therapy company’s current operating plan into late 2025.
Bluebird bio
Bluebird bio is a big name within the gene therapy sector, having already received three ex vivo gene therapy approvals from the U.S. Food and Drug Administration (FDA) for the treatment of rare genetic diseases such as beta thalassemia. The company is focused on gene addition and its approach to gene therapy involves using lentiviral vectors (LVVs) because it believes they have unique properties that are well-suited to treating a range of severe genetic diseases.
In 2022, Bluebird received two back-to-back approvals – the first was for ZYNTEGLO to treat beta-thalassemia, and the second was for SKYSONA to treat early, active cerebral adrenoleukodystrophy (CALD), a rare, progressive, neurodegenerative disease that primarily affects young boys.
The company’s latest approval then came in December 2023, after the FDA approved its treatment for sickle cell disease. The treatment, called LYFGENIA (also known as lovo-cel), is a one-time gene therapy that has the potential to resolve vaso-occlusive events and is custom-designed to treat the underlying cause of sickle cell disease, which is a complex and progressive genetic disease associated with unpredictable and debilitating vaso-occlusive events. LYFGENIA works by permanently adding a functional β-globin gene to patients’ own hematopoietic (blood) stem cells (HSCs).
CRISPR Therapeutics
Also a big name within the gene therapy sector, CRISPR Therapeutics is focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. The company has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases.
The company is applying gene editing to treat disease in two primary ways: targeting specific genes that cause or influence the course of a disease, and engineering the next generation of cell therapies that can address an array of diseases. In either case, the cells can be edited ex vivo or in vivo using the CRISPR/Cas9 delivery system.
It was CRISPR Therapeutics that, in partnership with Vertex Pharmaceuticals, received FDA approval in December for the first-ever CRISPR-based gene therapy, called CASGEVY. The gene therapy essentially works by turning on fetal hemoglobin, which makes it so that sickle cell disease or beta-thalassemia patients have no symptoms. More specifically, CASGEVY targets the BCL11A gene, as this is what usually prevents the production of fetal hemoglobin in adults.
Editas Medicine
Editas Medicine is focused on translating the power and potential of the CRISPR/Cas12a and CRISPR/Cas9 genome editing systems into a robust pipeline of treatments for people living with serious diseases around the world. While Cas9 is able to locate, bind to, and edit targeted genes, Cas12a greatly expands the range of ways that CRISPR gene editing can be used to produce genomic medicines. It provides researchers with more options for where and how to edit DNA and makes use of a shorter guide RNA than Cas9.
The gene therapy company is leveraging both ex vivo and in vivo approaches to develop their candidates. Its lead candidate is an ex vivo therapy called reni-cell, which is intended to treat sickle cell disease and beta-thalassemia. Reni-cel is currently in early-stage clinical trials and consists of patient-derived CD34+ hematopoietic stem and progenitor cells edited at the gamma globin gene (HBG1 and HBG2) promoters, where naturally occurring fetal hemoglobin (HbF) inducing mutations reside.
In December, it was announced that Vertex Pharmaceuticals would pay Editas up to $100 million for rights to Editas’ Cas9 gene-editing technology in a non-exclusive license agreement. As well as receiving $50 million in upfront cash, Editas is eligible to receive another $50 million through a contingent payment.
MeiraGTx
With a gene regulation platform technology that allows precise, dose-responsive control of gene expression by oral small molecules with a dynamic range that can exceed 5000-fold, MeiraGTx is a clinical-stage gene therapy company looking to develop treatments for patients suffering from a range of serious diseases. It has an initial focus on three distinct areas of unmet medical need, which include ocular diseases, neurodegenerative diseases, and severe forms of xerostomia – otherwise known as radiation-induced dry mouth.
The gene therapy company currently has six programs in clinical development, including a phase 3 clinical study for X-linked retinitis pigmentosa (XLRP) – an incurable genetic disease that causes blindness in men. The candidate being evaluated in this study is called bota-vec and is designed to treat the most common form of XLRP, which is caused by mutations in the eye-specific form of the RPGR gene, called RPGR open reading frame 15 (RPGR ORF15). Both rods and cones photoreceptors require RPGR ORF15 to function. Treatment with bota-vec has been found to have an acceptable safety profile, and efficacy assessments in its proof-of-concept study demonstrated improvements in retinal sensitivity, visual function, and functional vision.
In October 2023, MeiraGTx announced that it had received a $30 million strategic investment from Sanofi, giving Sanofi the right of first negotiation for the use of MeiraGTx’s Riboswitch gene regulation technology for certain immunology and inflammation and central nervous system (CNS) targets, as well as for GLP-1 and other gut peptides for metabolic disease, and MeiraGTx’s ongoing phase 2 program for the treatment of xerostomia.
Rocket Pharmaceuticals
Rocket Pharmaceuticals is advancing a sustainable pipeline of genetic therapies designed to correct the root cause of complex and rare disorders. The company uses a multi-platform approach that allows it to design the optimal gene therapy for each indication. Its pipeline is comprised of first-in-class gene therapies that incorporate both adeno-associated viral vector (AAV) and lentiviral vector (LVV) approaches to gene therapy.
Rocket’s LVV-based gene therapies target hematologic diseases and consist of late-stage programs for Fanconi anemia (FA) – a difficult-to-treat genetic disease that leads to bone marrow failure and potentially cancer – leukocyte adhesion deficiency-I (LAD-I) – a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal – and pyruvate kinase deficiency (PKD) – a monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia.
Meanwhile, its adeno-associated virus (AAV)-based portfolio targets cardiovascular indications, including a late-stage program for Danon disease – a devastating heart failure condition resulting in thickening of the heart – an early-stage program in clinical trials for PKP2-arrhythmogenic cardiomyopathy (ACM) – a life-threatening heart failure disease causing ventricular arrhythmias and sudden cardiac death – and a pre-clinical program targeting BAG3-associated dilated cardiomyopathy (DCM) – a heart failure condition that causes enlarged ventricles.
In one of the company’s more recent news announcements, in October 2023, Rocket announced that the FDA had accepted the Biologics License Application and granted Priority Review for RP-L201, the company’s LVV-based investigational gene therapy for severe LAD-I. The company announced positive topline safety and efficacy data for the therapy in 2022, from a phase 2 pivotal trial.
Sarepta Therapeutics
On a mission to engineer precision genetic medicine for rare diseases, Sarepta Therapeutics has a vast pipeline of more than 40 programs in various stages of development, driven by its multi-platform Precision Genetic Medicine Engine in gene therapy, RNA, and gene editing. Currently, Sarepta has one gene therapy and three RNA-based therapies on the market in the U.S.
Sarepta’s gene therapy, called ELEVIDYS, received accelerated approval from the FDA in June last year. Its approval made it the first gene therapy to treat duchenne muscular dystrophy (DMD). More specifically, it is an AAV-based gene therapy for the treatment of ambulatory pediatric patients aged four to five years-old with DMD who have a confirmed mutation in the DMD gene. It works by addressing the root genetic cause of DMD – mutations in the dystrophin gene that result in the lack of dystrophin protein – by delivering a gene that codes for a shortened form of dystrophin to muscle cells known as ELEVIDYS micro-dystrophin.
On February 16, the gene therapy company announced that the FDA had accepted its efficacy supplement to the Biologics License Application for ELEVIDYS, with the intention of broadening the approved indication of ELEVIDYS by removing age and ambulation restrictions and converting the approval from accelerated to traditional. The FDA is expected to review this by June 21.
Vertex Pharmaceuticals
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases, including cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia.
As mentioned previously, Vertex Pharmaceuticals co-developed the first-ever CRISPR-based gene therapy, CASGEVY, with CRISPR Therapeutics, for the treatment of sickle cell disease and beta-thalassemia. Vertex leads global development, manufacturing and commercialization of CASGEVY with support from CRISPR Therapeutics. In conjunction with the FDA approval of CASGEVY, Vertex will make a $200 million milestone payment to CRISPR Therapeutics, which will be capitalized and amortized to cost of sales. Additionally, Vertex will record 100% of CASGEVY revenues, costs of sales, and selling, general and administrative expenses, and will record CRISPR Therapeutics’ 40% share in the net profits or losses from CASGEVY within its cost of sales.
In 2019, the FDA also approved Vertex’s TRIKAFTA, for the treatment of cystic fibrosis in people aged 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is the most common cystic fibrosis-causing mutation.
Verve Therapeutics
Cardiovascular company Verve Therapeutics’ initial programs – VERVE-101, VERVE-102, and VERVE-201 – use a form of gene editing known as base editing. Base editing is a gene editing approach that enables precise and efficient editing at the single-base level in the genome without making a double-stranded break in the DNA. The company is advancing a pipeline of single-course in vivo gene editing programs intended to safely turn off genes in the liver that contribute to atherosclerotic cardiovascular disease (ASCVD) risk.
Its lead candidate, VERVE-101 is designed to be a single-course treatment that permanently turns off the PCSK9 gene in the liver to reduce disease-driving LDL-C, which is also referred to as ‘bad’ cholesterol. The reason for targeting the PCSK9 gene is because it is known to inhibit the removal of cholesterol from the blood, therefore raising the risk factors for developing cardiovascular problems. Additionally, individuals with mutations that disrupt the gene have been found to have lower cholesterol levels. VERVE-101 is currently being tested in a phase 1b trial in patients with heterozygous familial hypercholesterolemia (HeFH), an inherited genetic disorder that causes dangerously high cholesterol levels.
In November 2023, Verve published the first data on VERVE-101, providing the first clinical evidence that the treatment works as hoped. At the potentially therapeutic doses, the two patients treated with 0.45 mg/kg of VERVE-101 had a time-averaged LDL-C reduction of 39% and 48%, while the patient treated with 0.6 mg/kg had a time-averaged LDL-C reduction of 55% that was durable for 180 days, with more follow up to come.
Voyager Therapeutics
Voyager Therapeutics is dedicated to leveraging the power of human genetics to modify the course of, and ultimately cure, neurological diseases. The company’s pipeline includes both wholly owned and collaborative programs for Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, and various other CNS diseases. Many of its programs are derived from its TRACER (Tropism Redirection of AAV by Cell-type-specific Expression of RNA) AAV capsid discovery platform, which the company has used to generate novel capsids and identify associated receptors.
The TRACER platform is a broadly applicable, RNA-based screening platform that enables rapid discovery of AAV capsids with robust penetration of the blood-brain barrier. In preclinical studies, TRACER-generated capsids have demonstrated widespread gene expression in the CNS compared to conventional AAV capsids as well as cell- and tissue-specific transduction, including to areas of the brain that have been traditionally difficult to reach, while de-targeting the liver and dorsal root ganglia, which emerge from the dorsal root of the spinal nerves and carry sensory messages from various receptors.
In January, Voyager announced that it would pay $100 million upfront as part of a licensing deal to develop gene therapy candidates for genetic disorders. The gene therapy company would provide Novartis access to its RNA-based screening platform – which helps in rapid discovery of experimental gene therapies – and would also be eligible for tiered royalties on global sales of products developed using the platform. As part of the deal, Voyager would also be eligible to receive up to $1.2 billion on achieving certain milestones.
Gene therapy: a thriving market
The gene therapy market is continuing to multiply in size. According to Precedence Research, the global gene therapy market was valued at $7.74 billion in 2023, and is expected to reach over $38.76 billion by 2032. This would mean that the market is poised to grow at a registered compound annual growth rate (CAGR) of 19.60% from 2023 to 2032. And it is likely that, as the market grows, we will see even more gene therapy companies join the race to develop innovative treatments targeting the root cause of a range of different diseases.