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In 2023, the FDA Center for Biologics Evaluation and Research (CBER) approved 5 genes** (cell-free**, small nucleic acid drugs), a record number.
In 2017, the U.S. FDA approved Luxturna, the gene for Spark Therapeutics** hereditary eye diseases, becoming the first gene approved by the FDA for genetic diseases**. However, the number of genes** approved in the following years was very small, until 4 and 5 genes** were approved in 2022 and 2023 respectively, revealing that this type of new drug has finally ushered in an explosive period.
Table 1U.S. FDA Approved Gene**
Does not contain cells**, small nucleic acid drugs).
Data**: Pharmaceutical intelligence data, pharmaceutical intelligence headline collation.
Most of these genes have been recognized as "orphan drugs" and "major breakthrough drugs", and their approval for marketing is of great significance to patients.
On the other hand, there is a lot of controversy over the high pricing of genetics. However, genetics belong to personalized and precision medicine, which not only has a high cost, but also a small number of patients, and the pricing of pharmaceutical companies to recover R&D costs is bound to be high, and there is no possibility of decline in the short term. According to the author's statistics, the first gene ** Luxturna approved by the FDA was priced at US$850,000 once, and among the genes** approved since then, 8 have exceeded US$2 million and reached a maximum of US$3.5 million (about 25 million yuan).
Although the price of gene** is high, with the support of the strong payment capacity of the U.S. pharmaceutical market, many expensive drugs still achieve good sales results. Novartis' Zolgensma, for example, achieved sales of 13$700 million, SARPTA's elevidys was only approved by the FDA in June 2023, and sales and delivery will be carried out in August 2023, achieving sales of 200.4 billion US dollars (about 14..)3.7 billion yuan).
luxturna
In December 2017, the FDA approved Spark Therapeutics (acquired by Roche) to develop a gene for specific hereditary eye diseases, Luxturna (Voretigene Neparvovec-Rzyl), which is the first gene for hereditary rare diseases marketed in the United States, and the first "direct administration" gene approved in the United States to target specific gene mutations.
A decrease or absence of RPE65 enzyme levels caused by a mutation in the RPE65 gene can lead to impaired vision and eventually blindness. Luxturna injects adeno-associated virus (**V) with the RPE65 gene directly into the eye to allow the normally functioning RPE65 gene to be expressed in retinal pigment epithelial cells, thereby restoring vision.
The unit price of the drug is 42$50,000 and $850,000 for both eyes**, but if the drug doesn't work, the full cost will not be charged. According to Spark's financial report, as of September 2019, Luxturna achieved net sales of $55 million. In October 2019, Roche announced the acquisition of Spark, and since then Roche has not disclosed the sales of Luxturna.
zolgensma
Zolgensma is a gene developed by Novartis and acquired by Exis for $8.7 billion in 2018. It was approved by the FDA in May 2019 for spinal muscular atrophy (SMA).
SMA, a rare inherited neuromuscular disorder, is the most common genetic disorder leading to death in children, caused by mutations in the SMN1 gene, which encodes motor neuron surviving protein. Zolgensma achieves sustained expression of SMN protein in a single intravenous injection, thereby halting disease progression.
Zolgensma Pricing 212$50,000, and Zolgensma achieved sales of 3 in the first year of listing$6.1 billion; In 2020, it reached 9$200 million; In 2021, it reached 13$5.1 billion; In 2022, it reached 13$700 million.
zynteglo
Zynteglo, developed by Bluebird Bio, is the first** gene drug for thalassemia, which was approved by the FDA in August 2022 for **thalassemia patients who need to receive routine red blood cell transfusions.
Zynteglo implants the gene expressing the normal hemoglobin subunit (A-T87Q-globin gene) into the hematopoietic stem cells taken from the patient in vitro through the lentiviral vector, and then transfuses these cells back into the patient.
The drug is priced at $2.8 million, but Zynteglo promises to refund 80% of the cost if it doesn't work. In the first three quarters of 2023, Zynteglo's sales were 867$80,000, about 3 to 4 patients received **.
skysona
Skysona is a one-time gene** developed by Bluebird Bio that was approved by the FDA in September 2022 for slowing disease progression in male patients aged 4-17 years with early active cerebral adrenal dysplasia (CALD).
Cald, an X-linked recessive neurodegenerative disease, is a more severe phenotype of adrenoleukodystrophy caused by mutations in the causative gene ABCD1. Skysona uses the Lenti-D lentiviral vector (LVV) for in vitro transduction to add a functional copy of the ABCD1 gene to the patient's own hematopoietic stem cells (HSCs), and the addition of the functional ABCD1 gene can produce the ALD protein in the patient's body. The goal of Skysona** is to stabilize the progression of CALD so that neurological function is preserved as much as possible, including motor function and communication.
The ** is priced at $3 million, with sales of $10.86 million in the first three quarters of 2023 and about 3 4 patients accepted**.
hemgenix
In June 2023, CSL Behring and Uniqure announced that the first patient received the hemophilia gene type B Hemgenix**, completing the first order of commercialization, which has not yet been widely promoted.
Hemgenti is a gene based on A**5 vector developed by CSL Behring, the drug is equipped with coagulation factor IX (FIX) gene variant (FIX-Padua), which is administered intravenously, and the gene can express FIX coagulation factor in the liver after administration, and then enters the blood to exert coagulation function, so as to achieve the purpose of **, theoretically a long-term effect of a dose. It was approved by the FDA in November 2022 for adult hemophilia patients who are in the stage of factor IX prophylactic transfusion, and who have had a life-threatening bleeding event or a recurrent and severe spontaneous bleeding event. This is the world's first gene for hemophilia B patients.
The product is priced at $3.5 million a dose, making it currently the most expensive drug in the world. Despite its high cost, CSL Behring believes the drug will "deliver significant cost savings for the entire healthcare system" and "significantly reduce the financial burden on people with hemophilia B by reducing annual bleeding rates, reducing or eliminating prophylactic** and maintaining high factor ix levels for many years."
adstiladrin
Adstiladrin (Nadofaragene Firadenovec) was developed by Ferring Pharmaceuticals and approved by the US FDA in December 2022 for adult patients with carcinoma in situ (CIS) and/or non-papillary tumors of high-risk non-muscle-invasive bladder cancer (NMIBC) that is ineffective with bacillus calmette-de-Guérin (BCG). This is the first gene to be approved for bladder cancer**.
NMIBC is a subtype of bladder cancer, it is also known as "superficial" bladder cancer, and about 75% of people newly diagnosed with bladder cancer have NMIBC. BCG (Bacillus Calmette-Guérin syndrome) remains the first-line standard** for patients with high-grade NMIBC. However, more than 50% of patients who receive BCG initial** will develop disease** and progression within one year, and many of them will develop disease that does not respond to BCG. Adstiladrin is a non-replicating adenoviral vector-based gene** containing the interferon ALFA-2B gene, a novel gene** approach that transforms a patient's own bladder wall cells into an interferon microfactory, thereby enhancing the body's natural defenses against cancer.
Adstiladrin is administered by intravesical infusion every 3 months and is priced at $60,000 per unit dose.
vyjuvek
Vyjuvek is a topical gene** developed by Krystal Biotech that was approved by the FDA in May 2023 for dystrophic epidermolysis bullosa (DEB) 6 months of age and older. This is the first FDA-approved reproducible topical gene** and the first approved gene** for DEB patients.
Patients with DEB, also known as "butterfly babies", are a rare hereditary disease caused by one or more mutations in the Col7A1 gene. Lack of functional anchor fibers in patients results in breakage, blistering, or tearing of the mucous membranes after minor trauma or friction.
Vyjuvek uses herpes simplex virus type 1 (HSV-1) as a gene delivery vehicle, which is used approximately once a week and can be applied directly to the wound of the patient, by restoring the expression of col7 in the patient's keratinocytes and fibroblasts. Data from the Vyjuvek clinical trial showed that topical administration of B-VEC** significantly improved complete wound healing at 3 and 6 months in patients with DEB.
The drug is priced at $24,250 per bottle, and patients use an average of 26 bottles per year, at a cost of about $630,000 per year, which is $48 after a mandatory discount$50,000.
elevidys
Elevidys is a gene replacement jointly developed by Salipta Therapeutics and Roche, which was approved by the FDA in June 2023 for patients with Duchenne muscular dystrophy aged 4 to 5 years. This is the world's first one-time gene for Duchenne muscular dystrophy (DMD).
DMD is a fatal and rare X-linked degenerative neuromuscular disease that occurs in men, due to the mutation or deletion of the dystrophin gene in the patient's body, the corresponding protein cannot be produced to maintain the stability of the cell membrane of skeletal muscle and other tissues, resulting in atrophy or degeneration of muscle tissue, and eventually death due to respiratory or heart failure. By infusing normal genes into patients, Elevidy helps children continue to produce recombinant proteins with dystrophin function.
Prior to the approval of elevidys, there were 4 DMD "exon jumps" in the world, 3 of which came from the company Sarepta. However, these ** need to be administered by regular injections, and the clinical efficacy is not ideal. The goal of elevidys as a gene replacement** is to enable a one-time dose that will radically replace the defective gene, regardless of where the patient's gene mutation occurs in the dystrophin gene. The ** is priced at $3.2 million per shot. In August 2023, elevidys carried out sales and delivery, and the sales of elevidys in 2023 will be about 200 million US dollars (about 1.4 billion yuan).
roct**ian
Roct**ian (Valoctocogene Roxaparvovec) is a gene** developed by Biomarin, which was approved by the FDA in June 2023 as a one-time single-dose infusion for severe hemophilia A. This is the first FDA to approve the gene for patients with severe hemophilia A.
Hemophilia A (HA) is a rare inherited bleeding disorder in which adults with severe hemophilia A face a lifelong burden, require frequent fluids, and are at high risk of health complications. Roct**ian is a gene** that uses the A**5 viral vector to deliver a transgene expressing clotting factors, designed to replace the function of the mutant gene, enabling patients with severe hemophilia A to produce their own FVIII, thereby limiting bleeding events. The price of ROCT**ian is $2.9 million, although it is expensive, but if the patient can restore a certain level of clotting factors without repeated infusions, the patient can still benefit considerably.
lyfgenia
lyfgenia（lovo-cel；Lovotibeglogene Autotemcel) is a one-time gene** developed by Bluebird Bio and approved by the FDA in December 2023 for sickle cell disease (SCD) patients aged 12 years and older with ** vaso-occlusive crisis (VOC).
Lyfgenia is a lentiviral vector-based cell gene** that permanently adds a functional globin gene to a patient's own hematopoietic stem cells (HSCs) through a lentiviral vector to produce hemoglobin (HBAT87Q) with anti-sickle cell properties that have similar oxygen-binding capacity to wild-type HBAs, limit erythrocyte sickleness, and potentially reduce vaso-occlusive events (VOE) methods. At $3.1 million, it is the third most expensive on the market.
casgevy
In November 2023, the world's first CRISPR Cas9 gene-editing drug, Casgevy (Exa-Cel; Exagamglogene Autotemcel) is approved for marketing in the UK for patients aged 12 years and older with transfusion-dependent thalassemia (TDT) or sickle cell disease (SCD) with a vaso-occlusive crisis (VOC). On December 8, Casgevy was approved by the US FDA for SCD, and in January 2024, the FDA approved TDT.
Casgevy is an autologous, EX vivo CRISPR Cas9 gene editing drug jointly launched by CRISPR Therapeutics and Vertex, which needs to extract the patient's own hematopoietic stem cells, and then deliver the CRISPR Cas9 system to hematopoietic stem cells by electroporation, targeting the BCL11A red blood cell line-specific enhancer and specifically silencing the BCL11A gene. Reactivates fetal hemoglobin (HBF) production and expression of high levels of HBF, thereby alleviating the need for blood transfusion in patients with TDT and reducing pain and vaso-occlusive crisis in patients with SCD.
CRISPR Cas9 is currently the mainstream gene editing technology, and the approval of Casgevy is another milestone in the field of marker genes.
Casgevy is priced at $2.2 million at a one-time price, down from $3.1 million for Bluebird's SCD gene Lyfgenia and $2.8 million for the TDT gene Zynteglo.
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