Monthly News Roundup - June 2023
Medically reviewed by Drugs.com.
Elevidys is First Gene Therapy Cleared to Treat Duchenne Muscular Dystrophy
In June, the FDA granted accelerated approval of Elevidys (delandistrogene moxeparvovec-rokl) from Sarepta Therapeutics, Inc. Elevidys is an adeno-associated virus vector-based gene therapy indicated for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene.
- Duchenne Muscular Dystrophy (DMD) is the most common childhood form of muscular dystrophy and typically occurs in boys. It is an inherited degenerative disease that results in muscle weakness and loss of muscle tissue, which worsens over time. The average life expectancy is about 27 years.
- DMD is caused by a mutation in the dystrophin gene that results in the lack of dystrophin protein, needed to strengthen muscle fibers and protect them from injury. Elevidys is designed to treat the underlying cause of DMD by delivering a gene that codes for a functional shortened dystrophin (called Elevidys micro-dystrophin) into the muscle tissue.
- Patients selected for treatment have anti-AAVrh74 total binding antibody titers <1:400. Elevidys is given as a one-time, single-dose intravenous (IV) infusion over 1 to 2 hours. One day prior to Elevidys infusion, initiate a corticosteroid regimen for a minimum of 60 days.
- Elevidys should not be used in patients with any deletion in exon 8 and/or exon 9 in the DMD gene. Warnings include acute serious liver injury, immune-mediated myositis (muscle inflammation) and myocarditis (heart muscle inflammation). Common side effects include vomiting and nausea, elevated liver enzymes or total bilirubin, pyrexia (fever), and thrombocytopenia (low platelet counts).
- Accelerated approval was based on expression of Elevidys micro-dystrophin observed in patients treated with Elevidys. Continued approval may depend upon further clinical trial results from the Phase 3 EMBARK trial, expected in late 2023.
Amgen’s Blincyto Granted Full Approval for MRD-positive B-cell Precursor ALL
Blincyto (blinatumomab), a bispecific CD19-directed CD3 T-cell engager (BiTE) immunotherapy, is now fully FDA-approved to treat CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) adults and pediatric patients in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. ALL is a type of blood and bone marrow cancer. MRD disease is at risk of a relapse due to remaining leukemia cells after previous treatment.
- Blincyto is a BiTE (bispecific T-cell engager) immunotherapy. It targets the CD19 antigens on B cells (a type of white blood cell). BiTE therapies fight cancer by boosting the immune system’s ability to detect and kill cancer cells.
- Conversion from accelerated to full approval was based on additional data from two Phase 3 studies. In the BLAST study, effectiveness in patients ≥ 18 years of age with MRD-positive B-cell precursor ALL was based on achievement of undetectable MRD within one cycle of treatment and hematological relapse-free survival (RFS). The treated population included 86 patients in first (n=61) or second (n=25) hematologic complete remission (CR1 or CR2). In CR1 and CR2, a complete MRD response was seen in 85.2% and 72% of patients, respectively. Median hematological relapse-free survival in CR1 and CR2 was a median of 35.2 and 12.3 months, respectively.
- The most common adverse reactions (≥ 20%) in studies were pyrexia (fever), infusion-related reactions, infections, headache, neutropenia (low white blood cells), anemia (low red blood cells), and thrombocytopenia (low platelets). Warnings include infections, effect on driving or hazardous activities, pancreatitis and fetal harm, among others.
- In 2017, Blincyto also received full approval for relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adults and pediatric patients.
Genentech’s Bispecific Antibody Columvi Cleared for Diffuse Large B-Cell Lymphoma
In June, the FDA granted accelerated approval to Genentech’s Columvi (glofitamab-gxbm) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy. Continued approval for this use may be dependent upon further confirmatory studies.
- Large B-cell lymphoma is an aggressive type of non-Hodgkin’s lymphoma (NHL) resulting from the proliferation of cancerous B cells during development. DLBCL is an aggressive, hard-to-treat disease and is the most common form of non-Hodgkin’s lymphoma in the United States.
- Columvi is a bispecific CD20-directed CD3 T-cell engager monoclonal antibody. It binds at two receptor sites: CD20 on B cells and CD3 on T cells to kill the cancer-causing B cells.
- Accelerated approval was based on the 8-month, Phase I/II NP30179 study in 132 patients with R/R DLBCL (~30% had received prior CAR T-cell therapy). Results showed patients treated with Columvi achieved a 43% complete response rate (primary endpoint) and a 56% overall response rate. About 68% of those who responded continued to respond for at least 9 months and the median duration of response was 1.5 years.
- Columvi is dosed in 21-day treatment cycles. Pretreatment with obinutuzumab (Gazyva) is given 7 days before initiation of Columvi. Columvi is then administered as 13 intravenous (IV) infusions over a maximum of 12 cycles (including step-up dosing), or until disease progression or intolerance to treatment, whichever occurs first. Columvi is administered as step-up dosing with premedications to reduce the risk of cytokine release syndrome (CRS) and infusion reactions.
- The most common adverse events (AEs) include: CRS (70%), which may be serious or life-threatening, musculoskeletal pain (21%), fatigue (20%) and rash (20%). CRS was generally low grade (52% experienced Grade 1; 14% experienced Grade 2).
Pfizer’s Litfulo is First Option for Teens with Severe Alopecia Areata
In June, the FDA cleared Pfizer’s Litfulo (ritlecitinib), an oral, once-daily treatment for severe alopecia areata in adults and adolescents 12 years and older. Litfulo inhibits Janus kinase 3 (JAK3) and tyrosine kinases expressed in the hepatocellular carcinoma (TEC) family of kinases (TEC). It is thought to work by blocking the activity of cytokine proteins and immune T cells.
- Alopecia areata, an autoimmune disease, results in patchy or complete hair loss, often on the scalp, face, or body. It is caused by an immune attack on the hair follicles which causes the hair to fall out. Many people start showing signs as early as their teens.
- In the Phase 2b/3, pivotal, randomized, placebo-controlled ALLEGRO Trial, Litfulo met the primary efficacy endpoint of improving scalp hair regrowth. In the study, 718 patients 12 years and older with alopecia areata who had at least 50% hair loss of the scalp as measured by the Severity of Alopecia Tool (SALT) score were evaluated. A statistically significant proportion of patients who took Litfulo 50 mg once daily (23%) had 20% or less scalp hair loss after 24 weeks of treatment compared with placebo (1.6%).
- The most common adverse reactions included headache (10.8%), diarrhea (10%), acne (6.2%), rash (5.4%), and hives (4.6%). Warnings include increased risk of serious infections, death in people 50 years and older with at least one heart disease risk factor, cancer and immune system problems, blood clots and severe allergies.
- Pfizer states Litfulo is expected to be commercially available in the coming weeks.
FDA Approves Lodoco as the First Anti-Inflammatory Drug for Heart Disease
This past month the FDA approved AGEPHA Pharma’s Lodoco (colchicine) for adults with cardiovascular (heart) disease to reduce the risk of heart attack, stroke, coronary revascularization procedures, and cardiovascular death. It is used in patients with established plaque build-up in their arteries or other factors for heart disease.
- Inflammation plays a large role in heart disease and plaque build-up. Clinical data has shown that colchicine reduces high sensitivity C-reactive protein, possibly through inhibition of microtubule assembly and subsequent prevention of neutrophil (a type of white blood cell) activity.
- Priority approval was supported by data from a randomized, placebo-controlled trial with 5,522 patients with heart disease taking standard treatments, such as high-dose statins. Colchicine 0.5 mg orally once daily significantly reduced the overall risk of cardiovascular death, heart attack, stroke, or revascularization procedures by 31% compared to the placebo group when added to high-intensity statins and other prevention therapies.
- Common side effects include gastrointestinal (stomach) symptoms such as diarrhea, vomiting, abdominal cramping, and myalgia (muscle pain). Patients with kidney failure or severe liver disease should not take Lodoco.
- Lodoco is the first anti-inflammatory atheroprotective cardiovascular treatment to be FDA-approved. It’s expected to be commercially available in the second half of 2023.
FDA Approves Vyvgart Hytrulo Subcutaneous Injection for Myasthenia Gravis
The FDA has cleared Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) from Halozyme Therapeutics, a subcutaneous (under the skin) injection to improve muscle weakness in adults with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive.
- Vyvgart Hytrulo is a combination of efgartigimod alfa, a human IgG1 antibody fragment, and recombinant human hyaluronidase. Efgartigimod alfa works by lowering the amount of AChR antibodies that damage the acetylcholine receptor (AChR) located in muscles, which helps to improve muscle strength. Recombinant human hyaluronidase is used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously.
- This new dosage form may offer a time-saving advantage for patients and healthcare providers. Vyvgart Hytrulo is given by a healthcare professional as a 30 to 90 second subcutaneous injection once weekly over 4 weeks (with at least a 30 minute observation period for allergic reactions such as rash, angioedema, and dyspnea). Vyvgart, first approved in Dec. 2021, is given as an intravenous (IV) infusion over one hour with at least a one hour observation period.
- Warnings and precautions include infections and hypersensitivity (allergic) reactions. Common side effects include respiratory tract infections, headache, urinary tract infection, and injection site reactions.
FDA Approves Roctavian, First Gene Therapy for Severe Hemophilia A
In June, the FDA approved Roctavian (valoctocogene roxaparvovec-rvox) from BioMarin Pharmaceutical Inc. Roctavian is the first gene therapy to treat adults with severe hemophilia A (congenital factor VIII (FVIII) deficiency with FVIII activity < 1 IU/dL) without antibodies to adeno-associated virus serotype 5 (AAV5), as detected by an FDA-approved test.
- Hemophilia A, (also called FVIII deficiency or classic hemophilia), is a genetic disorder caused by missing or defective FVIII, a clotting protein. Lack of FVIII protein can cause painful and/or potentially life-threatening bleeding. In the most severe forms, painful, spontaneous bleeds into muscles or joints occur. Approximately 1 in 10,000 people have hemophilia A.
- Roctavian is given as a one-time, single-dose infusion. It works by delivering a functional gene that allows the body to produce FVIII on its own, limiting bleeding episodes and reducing the need for a lifetime of ongoing prevention treatments.
- Approval is based on data from the Phase 3 GENEr8-1 study. In 112 patients, an average 52% reduction in bleeding cases per year was seen, compared to bleeding while receiving routine FVIII prophylaxis (2.6 bleeds per year vs. 5.4 bleeds per year, respectively). The majority of participants continued to respond to Roctavian through 3 years, without supplemental use of regular prevention treatments.
- Warnings and precautions include infusion-related reactions, liver toxicity, blood-clotting events and theoretical risk of liver cancer. The most common side effects (≥ 5%) to Roctavian were nausea, fatigue, headache, infusion-related reactions, vomiting, and abdominal pain.
Posted June 2023
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