Here is information on the latest US FDA approvals, the week of March 18 – March 22, 2024
Nexletol and Nexlizet for LDL Lowering and CV Risk, Iclusig for ALL, Elahere for Ovarian Cancer, Duvyzat for DMD, Spevigo for Psoriasis, Tryvio for Hypertension, Opsynvi for PAH, Lenmeldy for Juvenile Metachromatic Leukodystrophy
Nexletol and Nexlizet for LDL Lowering and CV Risk
The FDA has approved bempedoic acid (Nexletol) as well as bempedoic acid plus ezetimibe (Nexlizet) both tablets for the reduction of cardiovascular risk and for the treatment of primary hyperlipidemia, either alone or in combination with statins. Bempedoic acid inhibits ATP citrate lyase, an enzyme involved in cholesterol synthesis, thereby reducing LDL-C levels. By contrast, ezetimibe works by preventing the absorption of cholesterol from the small intestine, which further lowers LDL-C levels. Combining these mechanisms may help lower LDL-C in patients who require additional treatment beyond statins or cannot tolerate statin therapy. These agents are the first LDL-C lowering non-statin medications indicated for primary prevention in patients at high risk of cardiovascular events but who have not yet experienced one. The approval was based on findings from the CLEAR Outcomes trial, which assessed the effect of bempedoic acid on cardiovascular outcomes in approximately 14,000 individuals with or at high risk of cardiovascular disease. The approval of bempedoic acid and bempedoic acid plus ezetimibe was granted to Esperion Therapeutics.
https://pi.esperion.com/nexlizet/nexlizet-pi.pdf
Iclusig for ALL
The FDA has granted accelerated approval to ponatinib (Iclusig) in combination with chemotherapy for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in previously untreated adults. Ponatinib is a tyrosine kinase inhibitor (TKI) that works by inhibiting the activity of BCR-ABL1, first approved for use in 2012. The latest approval makes ponatinib the first targeted agent approved in combination with chemotherapy for previously untreated Ph+ ALL. The accelerated approval was based on findings from the PhALLCON trial, an open-label phase 3 study involving 245 adults with newly diagnosed Ph+ ALL. The trial met its primary endpoint, demonstrating a significantly greater minimal residual disease (MRD)-negative complete remission (CR) rate in patients assigned to ponatinib (30% vs 12% with imatinib). As part of the accelerated approval process, confirmatory data may be required to verify the clinical benefit of ponatinib in this setting. In addition, with this latest indication, ponatinib was approved in Ph+ ALL as monotherapy for T315I-positive cases and for patients where no other TKIs are indicated as well as chronic myeloid leukemia (CML). The latest approval of ponatinib was granted to the manufacturer, Takeda.
https://www.iclusig.com/hcp/sites/default/files/2022-10/ICLUSIG-Prescribing-Information.pdf
Elahere for Ovarian Cancer
The FDA has approved mirvetuximab soravtansine-gynx (Elahere) for folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in adult patients treated with up to 3 prior therapies. This approval marks this agent as the first and only antibody-drug conjugate (ADC) in the U.S. for this malignancy, which initially received accelerated approval in November 2022. Mirvetuximab acts through a targeted approach by binding to the folate receptor alpha on cancer cells, delivering a potent cytotoxic agent to induce cancer cell death. Ovarian cancer is often diagnosed at a late stage and treated with platinum-based chemotherapy. However, many develop resistance to this chemotherapy. The full approval was based on results from the Phase 3 MIRASOL trial. The approval of was granted to AbbVie.
https://www.elahere.com/pdf/prescribing-information.pdf
Duvyzat for DMD
The FDA has approved givinostat (Duvyzat) for the treatment of patients 6 years or older with Duchenne muscular dystrophy (DMD), a rare X-linked progressive and life-limiting neuromuscular condition. Givinostat is a novel histone deacetylase (HDAC) inhibitor that mitigates muscle damage and slows DMD progression. Symptoms of DMD typically first appear between two and five years of age, with the disease eventually impairing mobility and affecting heart and respiratory muscles, leading to premature death. The approval was based on the results of the EPIDYS trial, a phase 3 study. The approval of givinostat was granted to Italfarmaco S.p.A., which has also established ITF Therapeutics in the U.S. to focus on rare diseases and lead the commercial launch of givinostat.
https://www.fda.gov/news-events/press-announcements/fda-approves-nonsteroidal-treatment-duchenne-muscular-dystrophy
Spevigo for Psoriasis
The FDA has approved spesolimab-sbzo (Spevigo) for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients aged ≥ 12 years who weigh ≥ 40 kg. This approval expands the indication for Spevigo, which was initially approved in September 2022 for treating flares of GPP. With this approval, Spevigo becomes the first targeted therapy available for both the acute and chronic treatment of GPP. Spevigo is an interleukin (IL)-36 receptor antagonist, involved in the cause of GPP. GPP is a rare and potentially life-threatening disease characterized by widespread pustules on a background of erythematous skin. The FDA’s decision for the expanded indication was based on the Effisayil 2 trial, a 48-week clinical study involving 123 patients. The trial demonstrated that individuals receiving Spevigo experienced a significant 84% reduction in GPP flares compared to those who received a placebo. Notably, among 30 participants who received a high dose of the treatment, no flares were observed after week 4. The approval of Spevigo was granted to Boehringer Ingelheim.
https://content.boehringer-ingelheim.com/DAM/18918a08-b1a0-44f0-8f01-af1e01236719/spevigo-us-pi.pdf
Tryvio for Hypertension
The FDA has approved aprocitentan (Tryvio) for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. This approval introduces aprocitentan as the first and only endothelin receptor antagonist for this indication, marking it as the first oral anti-hypertensive therapy that works via a new therapeutic pathway to be approved in nearly 40 years. Aprocitentan’s mechanism of action involves inhibiting the binding of endothelin (ET)-1 to ETA and ETB receptors, The approval was based on findings from the Phase 3 PRECISION trial, which showed that aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4, with a sustained effect at week 40. In this study, aprocitentan demonstrated its efficacy in patients with confirmed resistant hypertension, those who remained hypertensive despite being on a minimum of three antihypertensive drugs at optimal doses. The approval of aprocitentan was granted to Idorsia Pharmaceuticals US Inc.
https://www.idorsia.com/our-innovation/portfolio/aprocitentan
Opsynvi for PAH
The FDA has approved macitentan and tadalafil (Opsynvi) for the chronic treatment of adults with pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group I) and WHO functional class (FC) II-III. This marks the introduction of Opsynvi as the first and only once-daily single-tablet combination therapy for PAH patients, suitable for those who are treatment-naïve or already on an endothelin receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, or both. Opsynvi combines macitentan, an endothelin receptor antagonist, with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor, targeting two critical pathways in the pathophysiology of PAH. PAH is a chronic and progressive disease characterized by the elevation of blood pressure in the pulmonary arteries, leading to right heart failure and reduced exercise capacity. The approval of Opsynvi was based on findings from the pivotal Phase 3 A DUE study, which demonstrated that this agent provided a greater reduction in pulmonary vascular resistance (PVR) after 16 weeks compared to either tadalafil or macitentan monotherapy. The FDA granted the approval to Johnson & Johnson.
https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/OPSYNVI-pi.pdf
Lenmeldy for Juvenile Metachromatic Leukodystrophy
The FDA has approved atidarsagene autotemcel (Lenmeldy) for children with pre-symptomatic late infantile, pre-symptomatic early juvenile, or early symptomatic early juvenile metachromatic leukodystrophy (MLD). This is the first FDA-approved gene therapy for MLD, a rare genetic disease that affects the brain and nervous system due to a deficiency of the enzyme arylsulfatase A (ARSA), leading to the accumulation of sulfatides in cells. This buildup causes damage to the central and peripheral nervous system, resulting in loss of motor and cognitive function and early death. Lenmeldy is a one-time, individualized gene therapy that uses the patient’s own hematopoietic (blood) stem cells, which are genetically modified to include a functional copy of the arylsulfatase A gene. These modified stem cells are then transplanted back into the patient, where they produce the ARSA enzyme, helping to break down sulfatides and potentially stopping the progression of MLD. Treatment with Lenmeldy requires the patient to first undergo high-dose chemotherapy to prepare the bone marrow for the modified cells. The approval of Lenmeldy was based on data from 37 children treated in two single-arm, open-label clinical trials and an expanded access program. Treatment with Lenmeldy significantly reduced the risk of severe motor impairment or death compared to untreated children, with notable improvements in survival, mobility, and cognitive functions. The FDA granted the approval of Lenmeldy to Orchard Therapeutics.
https://ir.orchard-tx.com/news-releases/news-release-details/orchard-therapeutics-receives-fda-approval-lenmeldytm