01
Kymriah
Kymriah (tisagenlecleucel) is a CD19-directed CAR-T cell therapy developed by Novartis for the treatment of certain types of blood cancer. The therapy has received multiple approvals from the U.S. Food and Drug Administration (FDA) for different indications:
- The first approval was granted on August 30, 2017, for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or has relapsed at least twice.
- A second indication was approved on May 2, 2018, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after at least two lines of systemic therapy.
- The most recent approval for Kymriah came on May 28, 2022, for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received two or more lines of systemic therapy.
Kymriah is a one-time treatment that involves the collection of a patient’s T-cells, which are genetically modified to target the CD19 protein on cancer cells, and then reinfused back into the patient. It represents a significant advancement in the field of immunotherapy and has demonstrated efficacy in providing durable responses for patients with these aggressive and often treatment-resistant forms of cancer.
02
Yescarta
Yescarta (axicabtagene ciloleucel) is a CAR-T cell therapy developed by Kite Pharma, a subsidiary of Gilead Sciences. It has been granted approval by the U.S. Food and Drug Administration (FDA) for several indications:
- The initial approval was received on October 18, 2017, for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after at least two lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
- An expanded indication was approved on March 2021, for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least two lines of systemic therapy.
- In April 2022, Yescarta received an additional approval as a second-line treatment for adult patients with large B-cell lymphoma (LBCL) who are refractory to first-line chemo-immunotherapy or who relapse within 12 months after first-line chemo-immunotherapy.
Yescarta is a CD19-directed therapy that involves the collection and modification of a patient’s T-cells to target and eliminate cancer cells. It represents a significant development in the field of immuno-oncology, offering a potentially curative treatment option for patients with aggressive forms of lymphoma. The approval of Yescarta for these indications has been supported by clinical trials demonstrating its efficacy and safety in the respective patient populations.
03
Luxturna
Luxturna (voretigene neparvovec-rzyl) is a gene therapy developed by Spark Therapeutics for the treatment of patients with inherited retinal disease (IRD) caused by mutations in the RPE65 gene. It is the first in vivo gene therapy to be approved by the U.S. Food and Drug Administration (FDA), which granted its approval on December 19, 2017 . The therapy is indicated for the treatment of children and adults with confirmed biallelic RPE65 mutation-associated retinal dystrophy, a form of IRD that can lead to blindness .
Luxturna works by delivering a healthy copy of the RPE65 gene to the retinal cells, allowing them to produce the functional RPE65 protein necessary for normal vision. The treatment involves a one-time administration via subretinal injection to each eye, with the second eye treated at least six days after the first . The most common adverse reactions associated with Luxturna include conjunctival hyperemia, cataract, increased intraocular pressure, and retinal tear . The approval of Luxturna represents a significant milestone in the field of gene therapy, demonstrating the potential of this approach to treat a wide range of challenging diseases .
04
Zolgensma
Zolgensma (onasemnogene abeparvovec-xioi) is a gene therapy developed by Novartis Gene Therapies, Inc. for the treatment of spinal muscular atrophy (SMA). It is specifically indicated for pediatric patients less than 2 years of age with SMA who have bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
The therapy was first approved by the U.S. Food and Drug Administration (FDA) on May 24, 2019. The target for Zolgensma is the SMN1 gene, which is responsible for producing the survival motor neuron (SMN) protein essential for the normal functioning of motor neurons. The therapy works by delivering a functional copy of the human SMN gene into the target motor neuron cells, which can help improve muscle movement and function, and enhance the survival of these cells in patients with SMA .
05
Tecartus
Tecartus (brexucabtagene autoleucel) is a CD19-directed CAR-T cell therapy developed by Kite Pharma, a subsidiary of Gilead Sciences. It has been granted approval by the U.S. Food and Drug Administration (FDA) for two indications:
1. The first approval was for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL), and this milestone was achieved on July 24, 2020. Tecartus is the first and only CAR-T cell therapy approved for this patient population .
2. The second approval, which came on October 1, 2021, is for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Tecartus is also the first CAR-T cell therapy approved for the treatment of adult patients with ALL .
The target for Tecartus is the CD19 protein, which is expressed on the surface of B cells, including abnormal B cells found in certain B-cell lymphomas and leukemias. The therapy involves the collection of a patient’s T cells, which are then genetically modified to produce a protein that targets CD19, enabling the T cells to recognize and destroy CD19-positive cancer cells .
06
Breyanzi
Breyanzi (lisocabtagene maraleucel), developed by Bristol Myers Squibb, is a CD19-directed CAR-T cell therapy. It received accelerated approval from the U.S. Food and Drug Administration (FDA) on February 5, 2021. The indication for Breyanzi is for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after at least two lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), high-grade B-cell lymphoma, and DLBCL arising from indolent lymphoma.
Breyanzi is a one-time treatment that involves collecting a patient’s T-cells, modifying them to target the CD19 protein on cancer cells, and then infusing these modified cells back into the patient to fight the cancer. Its approval was based on data from a multicenter clinical trial demonstrating the efficacy and safety of the therapy in treating the specified patient population.
07
Abecma
Abecma (idecabtagene vicleucel, ide-cel) is a BCMA-directed CAR-T cell therapy developed by Bristol Myers Squibb in collaboration with Bluebird Bio. It received accelerated approval from the U.S. Food and Drug Administration (FDA) on March 27, 2021 . The indication for Abecma is for the treatment of adult patients with relapsed or refractory multiple myeloma (MM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and a monoclonal antibody directed against CD38 .
The recommended dose of Abecma is 300-460 x 10^6 CAR-positive T cells, which is an autologous treatment, meaning the therapy uses the patient’s own genetically modified T-cells to target and kill cancer cells expressing BCMA. Abecma is the first BCMA-directed CAR-T cell therapy to be approved globally, offering a new personalized treatment option for patients with multiple myeloma who have exhausted other treatment options.
08
Carvykti
Carvykti (ciltacabtagene autoleucel, also known as cilta-cel) is a BCMA-directed CAR-T cell therapy developed by Legend Biotech in collaboration with Janssen Pharmaceuticals. It received accelerated approval from the U.S. Food and Drug Administration (FDA) on February 28, 2022. The indication for Carvykti is for the treatment of adult patients with relapsed or refractory multiple myeloma (MM) who have received four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and a monoclonal antibody directed against CD38 .
In addition, on April 5, 2024, the FDA expanded the indication for Carvykti to include the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who have previously received at least one line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and are refractory to lenalidomide . This made Carvykti the first and only BCMA-targeted therapy approved for second-line treatment of multiple myeloma patients, encompassing CAR-T therapies, bispecific antibodies, and antibody-drug conjugates (ADCs).
09
Zynteglo
Zynteglo (betibeglogene autotemcel, beti-cel), developed by bluebird bio, is a one-time gene therapy for the treatment of adult and pediatric patients with transfusion-dependent β-thalassemia (TDT) who require regular blood transfusions. It was approved by the U.S. Food and Drug Administration (FDA) on August 17, 2022 . The therapy involves extracting the patient’s own hematopoietic stem cells, modifying them with a functional copy of the βA-T87Q-globin gene using a lentiviral vector, and then reintroducing these cells back into the patient to produce hemoglobin and reduce the need for transfusions.
Zynteglo’s approval was based on data from two multicenter clinical studies that included adult and pediatric patients with TDT who required regular blood transfusions. Efficacy was determined by the achievement of transfusion independence, defined as maintaining a predefined hemoglobin level without any red blood cell transfusions for at least 12 months. Among the 41 patients treated with Zynteglo, 89% achieved transfusion independence . The therapy is considered a significant milestone in the field of gene therapy and offers a new treatment paradigm for patients with this serious genetic disease .
10
Skysona
Skysona (elivaldogene autotemcel, also known as Lenti-D) is an autologous hematopoietic stem cell-based gene therapy developed by bluebird bio. It is indicated to slow the progression of neurologic dysfunction in boys aged 4-17 years with early, active cerebral adrenoleukodystrophy (CALD). This approval is based on the 24-month Major Functional Disability (MFD)-free survival data, and the therapy has the potential to have a lifelong effect on the treatment of CALD .
Skysona was approved by the European Commission on July 21, 2021, making it the first and only gene therapy approved in the European Union for the treatment of early CALD in patients under the age of 18 who do not have a matched sibling donor . The U.S. Food and Drug Administration (FDA) granted accelerated approval for Skysona on September 16, 2022 . The therapy involves using the patient’s own cells, which are modified to carry a functional copy of the ABCD1 gene, helping to combat the toxic accumulation of very-long-chain fatty acids that characterize CALD. Skysona’s approval represents a significant advancement in the treatment of this rare and rapidly progressive neurological condition.
11
Hemgenix
Hemgenix (etranacogene dezaparvovec) is a gene therapy developed by uniQure and commercialized by CSL Behring. It is indicated for the treatment of adults with hemophilia B, a hereditary bleeding disorder characterized by a lack or deficiency of clotting factor IX. Hemgenix was approved by the U.S. Food and Drug Administration (FDA) on November 22, 2022 . The therapy involves a single intravenous infusion of the AAV5 vector carrying a gene variant that results in the production of factor IX in the liver, which can significantly reduce or even eliminate the need for routine infusions of factor IX replacement therapy.
Hemgenix’s approval was based on clinical trials demonstrating that a one-time infusion led to a sustained increase in factor IX activity levels, effectively reducing the annualized bleeding rate (ABR) and allowing 94% of patients to discontinue prophylactic treatments. The most common adverse reactions associated with Hemgenix include elevated liver enzymes, headache, mild infusion-related reactions, and flu-like symptoms . It is worth noting that Hemgenix has been priced at $3.5 million, making it one of the most expensive drugs in the world.
12
Adstiladrin
Adstiladrin (nadofaragene firadenovec-vncg) is a prescription gene therapy used for the treatment of high-risk, non-muscle invasive bladder cancer (NMIBC) that has not responded to the standard treatment, Bacillus Calmette-Guérin (BCG). It is a non-replicating adenovirus vector-based gene therapy containing the gene for interferon alfa-2b, which is administered directly into the bladder every three months. The treatment delivers the interferon alfa-2b gene into the cells of the bladder wall, prompting the cells to secrete high quantities of interferon alfa-2b protein, which helps the body fight cancer.
It was developed by Ferring Pharmaceuticals.
13
Vyjuvek
Vyjuvek (beremagene geperpavec-svdt) is a gene therapy medication developed by Krystal Biotech for the treatment of dystrophic epidermolysis bullosa (DEB), a rare genetic skin disorder. It was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2023 . The approval marks Vyjuvek as the first and only gene therapy approved by the FDA for the treatment of recessive and dominant forms of DEB in patients who are six months of age and older .
The therapy works by delivering a functional copy of the COL7A1 gene to the skin cells, which helps in the production of type VII collagen, a protein essential for skin integrity. Vyjuvek is applied topically once a week to the patient’s wounds and is the first regenerative gene therapy that can be reapplied as needed .
The recommended dosage of Vyjuvek is based on the age of the patient, with a maximum dose of 1.6×10^9 PFU for those aged 6 months to less than 3 years, and 3.2×10^9 PFU for individuals 3 years and older . The treatment should be applied to wounds until closure, prioritizing newly reopened wounds, and should be administered under the guidance of a healthcare professional .
Common adverse reactions associated with Vyjuvek include itching, chills, redness, rash, cough, and rhinorrhea . The storage of Vyjuvek requires specific conditions; the medication should be stored at -15°C to -25°C, and if a freezer is not available, it can be refrigerated at 2°C to 8°C for up to one month .
For the most accurate and updated information regarding Vyjuvek’s approval date, indications, dosage, and administration, healthcare professionals and patients should refer to the official prescribing information provided by Krystal Biotech or the regulatory authority.
14
Elevidys
Elevidys (delandistrogene moxeparvovec-rokl, previously known as SRP-9001) is a gene therapy developed by Sarepta Therapeutics in collaboration with Roche. It is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients aged 4 years and above, who have a confirmed mutation in the DMD gene . Elevidys was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on June 23, 2023, and it became the first gene therapy approved to address the genetic root cause of the disease . The therapy works by delivering a shortened version of the dystrophin gene to muscle cells, potentially restoring the function lost due to the underlying genetic mutation that causes DMD .
In June 2024, the FDA fully approved Elevidys for patients aged 4 and above, regardless of their ability to walk, and also granted accelerated approval for patients who are unable to walk . The approval was based on data showing an increase in the expression of micro-dystrophin, a shortened functional version of the dystrophin protein, which Elevidys aims to produce in muscle cells . The most common adverse reactions reported with Elevidys include vomiting, nausea, elevated liver function test results, fever, and thrombocytopenia . It is important to note that Elevidys is contraindicated in patients with deletions of exon 8 and/or exon 9 of the DMD gene.
15
Roctavian
Roctavian (valoctocogene roxaparvovec) is a gene therapy developed by BioMarin Pharmaceutical Inc. for the treatment of adults with severe hemophilia A (factor VIII activity < 1 IU/dL) who have no detectable antibodies to adeno-associated virus 5 (AAV5) . It is the first gene therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of severe hemophilia A. The approval was granted on June 29, 2023.
The therapy involves a single intravenous infusion of the AAV5 vector carrying a gene that codes for a shortened version of the human factor VIII protein, which can help patients produce their own factor VIII, reducing or potentially eliminating the need for ongoing preventive treatments . The approval was based on data from the global Phase 3 GENEr8-1 study, which showed a significant reduction in the annualized bleeding rate (ABR) and the annualized factor VIII usage rate in patients treated with Roctavian . The therapy is priced at $2.9 million.
16
Lyfgenia
Lyfgenia (lovotibeglogene autotemcel, also known as lovo-cel) is a one-time gene therapy developed by bluebird bio for the treatment of sickle cell disease (SCD) in patients aged 12 years and older who have a history of vaso-occlusive events (VOEs). It was approved by the U.S. Food and Drug Administration (FDA) on December 8, 2023. The therapy works by using a modified form of the β-globin gene (βA-T87Q-globin gene), which is integrated into the patient’s own hematopoietic stem cells (HSCs), enabling the production of HbAT87Q hemoglobin that resists sickling of red blood cells, thereby reducing the frequency of sickle cells, hemolysis, and other complications .
The approval of Lyfgenia was based on data from the 1/2 phase HGB-206 study, where 94% of the 32 evaluable patients had complete resolution of severe VOEs, and 88.2% had no VOEs at all after infusion. The most common adverse reactions with an incidence of ≥20% and grade ≥3 were stomatitis, thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia . Additionally, the FDA has placed a warning on the label of Lyfgenia regarding the risk of blood cancer after two patients developed acute myeloid leukemia during the clinical trial phase . Patients treated with Lyfgenia are to be monitored for the rest of their lives for the development of cancerous malignancies .
17
Casgevy
Casgevy (exagamglogene autotemcel, also known as exa-cel) is a CRISPR/Cas9 gene editing therapy developed by Vertex Pharmaceuticals and CRISPR Therapeutics. It is indicated for the treatment of sickle cell disease (SCD) in adults and pediatric patients aged 12 years and older. The therapy was approved by the U.S. Food and Drug Administration (FDA) on December 8, 2023 .
Casgevy works by editing the patient’s hematopoietic stem cells to produce high levels of fetal hemoglobin (HbF), which can prevent the sickling of red blood cells and reduce the frequency of sickle cell crises. The approval of Casgevy marks a significant advancement in the field of gene therapy and offers a new treatment option for patients with SCD .
The therapy is priced at $2.2 million in the United States, making it an expensive but potentially curative option for eligible patients . It is also under review by other regulatory agencies and has the potential to be approved for use in more countries and regions .
18
Lenmeldy
Lenmeldy (atidarsagene autotemcel, also known as arsa-cel) is a gene therapy developed by Orchard Therapeutics for the treatment of children with early-onset metachromatic leukodystrophy (MLD), a rare and rapidly progressive neurodegenerative disorder. It was approved by the U.S. Food and Drug Administration (FDA) on March 18, 2024. The therapy is indicated for patients with presymptomatic late infantile, presymptomatic early juvenile, or early symptomatic early juvenile forms of MLD .
Lenmeldy works by using a lentiviral vector to deliver a functional copy of the ARSA gene into the patient’s own CD34+ hematopoietic stem cells, which are then reintroduced into the patient’s body to restore the production of the arylsulfatase A enzyme, thereby potentially halting the progression of the disease .
The approval was based on data from 37 pediatric patients with MLD who participated in two open-label clinical trials or received treatment under an expanded access protocol. The primary efficacy endpoint was the survival without severe motor disability, which was significantly improved in patients treated with Lenmeldy compared to untreated children .
The therapy is priced at $4.25 million, making it one of the most expensive drugs in history . The treatment’s most common adverse reactions include fever, low white blood cell count, oral ulcers, respiratory infections, rash, and other viral infections . It is important to note that Lenmeldy should be administered before symptoms appear or as early as possible after the first signs of the disease, as it may not be effective for patients already experiencing the effects of MLD .
19
Beqvez
Beqvez (fidanacogene elaparvovec-DZKT) is a gene therapy developed by Pfizer for the treatment of adults with hemophilia B. It is specifically indicated for adult patients (aged 18 and above) with moderate to severe hemophilia B who have a negative test for neutralizing antibodies to AAV serotype Rh74, and who are currently treated with factor IX (FIX) prophylaxis, or have a history of life-threatening bleeding, or have repeated serious spontaneous bleeding episodes .
The U.S. Food and Drug Administration (FDA) approved Beqvez on April 26, 2024. The therapy is administered as a single intravenous infusion and has the potential to provide long-term or even lifelong benefits with a one-time treatment, reducing the need for frequent infusions of clotting factor .
Beqvez is priced at $3.5 million, aligning with the price of Hemgenix, another gene therapy for hemophilia B that was approved earlier. The approval of Beqvez was based on the results from the BENEGENE-2 clinical study, an open-label, single-arm phase III trial that assessed the efficacy and safety of Beqvez in adult males with severe hemophilia B (defined as ≤2% FIX activity) .
Common adverse reactions reported with Beqvez include elevated liver enzymes. The product information includes warnings and precautions related to liver toxicity, infusion reactions, and the risk of malignancies such as liver cancer .
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