FDA Approved Drugs: August, 2023

Izervay (avacincaptad pegol sodium)

FDA approved Izervay, a complement C5 inhibitor, for the treatment of geographic atrophy secondary to age-related macular degeneration, according to a press release from Astellas Pharma.

The approval was based on the data from the GATHER1 and GATHER2 phase 3 clinical trials in which monthly 2 mg injections of Izervay (avacincaptad pegol intravitreal solution) showed a statistically significant reduction (P < .01) in the rate of geographic atrophy growth at 12 months. The slowing in disease progression was seen as early as 6 months, while up to a 35% reduction in progression occurred in the first year of treatment.

Talvey (talquetamab-tgvs)

FDA granted accelerated approval of Talvey (talquetamab-tgvs), a first-in-class bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.

Talvey is a bispecific T-cell engaging antibody that binds to the CD3 receptor on the surface of T cells and G protein-coupled receptor class C group 5 member D (GPRC5D) expressed on the surface of multiple myeloma cells, non-malignant plasma cells and healthy tissue such as epithelial cells in keratinized tissues of the skin and tongue.

Elrexfio (elranatamab-bcmm)

FDA granted accelerated approval to elranatamab-bcmm (Elrexfio, Pfizer, Inc.), a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Sohonos (palovarotene)

FDA approved Sohonos (palovarotene) capsules as a retinoid indicated for the reduction in volume of new heterotopic ossification in adults and pediatric patients aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP).

The FDA approval was based on the pivotal efficacy and safety data from the Phase 3 MOVE trial, the first and largest multicenter, open-label trial in adult and pediatric patients.

Veopoz (pozelimab-bbfg)

FDA approved Veopoz (pozelimab-bbfg) for the treatment of adult and pediatric patients 1 year of age and older with CHAPLE disease, also known as CD55-deficient protein-losing enteropathy. Veopoz is the first and only treatment indicated specifically for CHAPLE. Veopoz, a fully human monoclonal antibody, is designed to target complement factor C5, a protein involved in complement system activation.

The FDA approval was based on results from a Phase 2/3 open-label trial that investigated the efficacy and safety of pozelimab in 10 patients aged 3 to 19 (median of 8.5 years).

Eylea HD (aflibercept)

FDA approved EYLEA HD (aflibercept) Injection 8 mg for the treatment of patients with wet age-related macular degeneration (wAMD), diabetic macular edema (DME) and diabetic retinopathy (DR). This is the first and only treatment approved in wAMD and DME for immediate dosing at 8-week and up to 16-week intervals following three initial monthly doses

Approval was based on the pivotal PULSAR and PHOTON trials in which EYLEA HD demonstrated clinically equivalent vision gains to EYLEA (aflibercept) Injection 2 mg that were maintained with fewer injections.

Tyruko (natalizumab-sztn)

FDA approved biosimilar Tyruko (natalizumab-sztn), developed by Polpharma Biologics. Tyruko is approved to treat all indications covered by the reference medicine and is the first and only FDA-approved biosimilar for relapsing forms of multiple sclerosis (MS).

Sandoz entered into a global commercialization agreement for Tyruko with Polpharma Biologics in 2019. Under this agreement, Polpharma Biologics will maintain responsibility for development, manufacturing and supply of the active substance in Tyruko. Through an exclusive global license, Sandoz has the rights to commercialize and distribute it in all markets.

FDA Approved Drugs: March & April, 2023

Qalsody (tofersen)

Tofersen, an antisense oligonucleotide (ASO), is the first approved treatment for SOD1-ALS. In people with this form of the disease, mutations in their SOD1 gene cause their bodies to create a toxic form of SOD1 protein. This toxic protein causes motor neurons to degenerate, resulting in progressive muscle weakness. Tofersen is designed to bind to SOD1 mRNA and reduce SOD1 protein production.

In addition to the ongoing open label extension of the Phase III VALOR study, tofersen is being studied in the Phase 3 ATLAS study designed to evaluate whether tofersen can delay clinical onset when initiated in presymptomatic individuals with a SOD1 genetic mutation and biomarker evidence of disease activity. Biogen licensed tofersen from Ionis Pharmaceuticals, Inc. under a collaborative development and license agreement.

Joenja (leniolisib)

Joenja is the “first and only” oral, selective PI3Kδ inhibitor is the first and only treatment approved in the United States for APDS, a rare and progressive primary immunodeficiency. The FDA evaluated the Joenja application for APDS under Priority Review, which is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions.

Approval was based on findings from a multinational, triple-blind, placebo-controlled, randomized Phase II/III clinical trial, which evaluated efficacy and safety in 31 patients diagnosed with APDS aged 12 years and older. Also submitted as part of the application were data from a long-term, open-label extension clinical trial in which 38 patients received Joenja for a median of two years.

Rezzayo (rezafungin)

Rezzayo is an echinocandin antifungal indicated in patients who have limited or no alternative options for the treatment of candidemia and invasive candidiasis. Approval of this indication is based on limited clinical safety and efficacy data for Rezzayo. The FDA has approved Rezzayo as a once-weekly antifungal to treat invasive candidiasis and candidemia.

Last year, Melinta announced that it had acquired the exclusive rights to commercialize Rezzayo in the U.S. from Cidara. Cidara retains the rights to rezafungin in Japan and has licensed the commercial rights to Melinta Therapeutics in the U.S. and Mundipharma in all other geographies. The European Medicines Agency (EMA) accepted the marketing authorization application (MAA) for rezafungin in August 2022 and it is currently under review.

Zynyz (Retifanlimab-Dlwr)

Zynyz (retifanlimab-dlwr), a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), is FFDA approved for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). The Biologics License Application (BLA) for Zynyz for this indication has been approved under accelerated approval by the U.S. FDA based on tumor response rate and duration of response (DOR). Continued approval of Zynyz for this indication may be contingent on verification and description of clinical benefit in confirmatory trials.

The FDA approval was based on data from the POD1UM-201 trial, an open-label, multiregional, single-arm study that evaluated Zynyz in adults with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their advanced disease. Among chemotherapy-naïve patients (n=65), Zynyz monotherapy resulted in an objective response rate (ORR) of 52% (95% confidence interval [CI]: 40-65) as determined by independent central review (ICR) using RECIST v1.1. Complete response was seen in 12 patients (18%), and 22 patients (34%) showed partial response. Among the responding patients, the duration of response (DOR) ranged from 1.1 to 24.9+ months, and 76% (26/34) experienced a DOR of six months or longer, and 62% (21/34) experienced a DOR of 12 months or longer by landmark analysis.

Daybue (trofinetide)

Daybue is the “first and only” FDA approved treatment for Rett syndrome in adults and children 2 years of age and older. Trofinetide is a synthetic version of a naturally occurring molecule known as the tripeptide glycine-proline-glutamate (GPE). The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown.

The FDA approval of DAYBUE was supported by results from the pivotal Phase 3 LAVENDER study evaluating the efficacy and safety of trofinetide versus placebo in 187 female patients with Rett syndrome five to 20 years of age. In the study, treatment with DAYBUE demonstrated statistically significant improvement compared to placebo on both co-primary efficacy endpoints, as measured by the change from baseline in Rett Syndrome Behaviour Questionnaire (RSBQ) total score (p=0.018) and the Clinical Global Impression-Improvement (CGI-I) scale score (p=0.003) at week 12.

In 2018, Acadia entered into an exclusive license agreement with Neuren Pharmaceuticals Limited for the development and commercialization of trofinetide for the treatment of Rett syndrome and other indications in North America.

Zavzpret (zavegepant)

Zavzpret, is the “first and only” calcitonin gene-related peptide receptor antagonist nasal spray for treating migraines with or without an aura, or sensory disturbances such as flashes of light that can accompany a migraine.

Zavzpret began working to treat migraine symptoms in as little as 30 minutes and provided some relief for up to 48 hours after the last administered dose. A 10mg dose of the drug proved more effective than a placebo at relieving pain and other migraine symptoms.

Approval was based on the pivotal Phase III study, Zavzpret was statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptom at two hours post-dose. The pivotal study also demonstrated pain relief as early as 15 minutes in a prespecified secondary endpoint versus placebo.

Vitiligo Emerging Therapies

Vitiligo is a chronic disorder that causes areas of skin to lose color. When skin cells that make color are attacked and destroyed, the skin turns a milky-white color. Various factors such as autoimmune disease, genetic factors, & neurogenic factors lead to the development of Vitiligo. The main symptom associated with vitiligo is the loss of natural color. The patches can show up on any part of your body and can affect the skin, which gets milky-white patches, usually on the hands, feet, arms, and face, hair, which can turn white on the scalp, eyebrow, eyelash, and beard & the inside of your mouth or nose. People with vitiligo can also get problems with the eyes and ears. In addition, people with the disorder may worry about how their skin looks, which can affect general well-being.

Vitiligo is the most common skin depigmentation disorder with an average prevalence estimated to be between 0.5% to 2% of the global population. An estimated 65-95 million people of all ages, sexes, and ethnicities worldwide suffer from vitiligo, including approximately 2.4 million people in the United States. The majority (70–80%) of patients with vitiligo experience disease onset before age 30. Approximately 30% have childhood-onset vitiligo before age 12.

Currently, there are no FDA-approved therapies for vitiligo. Dermatologists typically prescribe topical corticosteroids, topical calcineurin inhibitors, and/or phototherapy for the treatment of vitiligo. Therefore, pharmaceutical companies such as Incyte Corporation, Dermavant Sciences GmbH, Aclaris Therapeutics, Inc. Amgen and other companies are developing novel therapies for the treatment of Vitiligo.

Incyte Corporation (Ruxolitinib/INCB018424)

Ruxolitinib is a Janus kinase (JAK1/JAK2) inhibitor discovered by Incyte scientists. Overactive signaling through the JAK-STAT pathway has been associated with many types of disease, including a group of rare blood cancers called myeloproliferative neoplasms (MPNs), as well also used for the treatment of Vitiligo. Ruxolitinib is currently under the clinical trial of Phase III. The purpose of this study is to evaluate the efficacy and safety of ruxolitinib cream in adolescent and adult participants with non-segmental vitiligo for whom total body involved vitiligo area (facial and nonfacial) does not exceed 10% body surface area (BSA).

Dermavant Sciences GmbH (Cerdulatinib 0.37% gel/DMVT-502)

Cerdulatinib is a dual inhibitor of the Janus kinase (JAK) and spleen tyrosine kinase (Syk) pathways, which Dermavant is evaluating as a differentiated topical treatment option for vitiligo and other inflammatory skin conditions such as atopic dermatitis. The Phase IIa study is a multi-center, randomized, double-blind, vehicle-controlled study to assess the safety, tolerability, and systemic exposure of cerdulatinib gel 0.37%, dosed twice daily for six weeks versus vehicle in 30 adult patients aged 18-70 years diagnosed with vitiligo. The primary endpoints of the study are the safety and tolerability of topical administration of cerdulatinib gel 0.37% in adult subjects with vitiligo assessed by frequency, duration, and severity of adverse events (local and systemic), vital signs, laboratory values, and local tolerability scale (LTS) scores.

Aclaris Therapeutics, Inc. (ATI-50002/ATI-502)

ATI-502 (AA-201 Topical), is an investigational topical Janus Kinase (JAK) 1/3 inhibitor, developed by aclaris therapeutics used to treat Vitiligo. Currently, ATI-502 is evaluated under the clinical trial study of Phase II. This is a multicenter, open-label study designed to evaluate the safety, tolerability, and efficacy of ATI-50002 Topical Solution 0.46% in subjects with non-segmental facial vitiligo. Subjects would be required to have a clinical diagnosis of non-segmental facial vitiligo affecting at least 0.25% of total body surface area (TBSA) (excluding upper and lower eyelids, mucosal lip areas, and forehead and chin areas covered by the stereotactic positioning device for photography) with at least one area of the face with normal pigmentation. Twenty-four eligible subjects would receive ATI-50002 Topical Solution, 0.46%, BID for 24 weeks.

Pfizer (PF-06651600)

PF-06651600 is an oral JAK3 inhibitor used to treat Vitiligo. The JAK pathways are believed to play an important role in inflammatory processes as they are involved in signaling for over 50 cytokines and growth factors, many of which drive immune-mediated conditions. JAK inhibition may offer patients with these conditions a potential new advanced treatment option.   PF-06651600 initiated a Phase II clinical trial study. This is a randomized, double-blind, parallel-group, multicenter study with an extension period. The study would have a maximum duration of approximately 60 weeks. This includes an up to 4 weeks Screening Period, a 24-week dose-ranging period, an up to 24 week extension period and an 8 week Follow up Period.

Amgen (AMG 714)

AMG 714 (PRV-015) is a human immunoglobulin monoclonal antibody that binds to IL-15 developed by amgen used to treat Vitiligo. Currently, AMG 714 is evaluated under a clinical trial study. The Phase IIa, double-blind, placebo-controlled, multi-center, proof of concept trial of AMG 714 for the treatment of vitiligo. Participants would be randomized 2:1 to receive AMG 714 or placebo for AMG714. The random assignment would be stratified by active versus stable vitiligo.

Vitiligo Emerging Pipeline Landscape

Company NameProduct NameMechanism of ActionRoute of AdministrationStage of Development
Incyte CorporationRuxolitinib/INCB018424JAK1/JAK2 InhibitorsTopicalPhase III
Dermavant Sciences GmbHCerdulatinib 0.37% gel/DMVT-502JAK/Syk InhibitorsTopicalPhase II
Aclaris Therapeutics, Inc.ATI-50002Janus kinase 1 Inhibitors; Janus kinase 3 InhibitorsTopicalPhase II
PfizerPF-06651600JAK3 InhibitorsOralPhase II
AmgenAMG 714Interleukin 15 InhibitorsSubcutaneousPhase II