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.

Cutaneous T-cell Lymphoma (CTCL): Market Size & Forecast

Cutaneous T-cell Lymphoma (CTCL): Market Size & Forecast

Disease Overview

Cutaneous T-cell Lymphoma (CTCL) is the most common type of skin lymphoma. CTCL is rare cancer that begins in white blood cells called T cells (T lymphocytes) and these the T cells develop abnormalities that make them attack the skin. It appears as an eczema-like skin rashes and can affect widespread parts of the body.

There are different types of Cutaneous T-cell Lymphoma (CTCL). Mycosis Fungoides and Sezary syndrome are the most frequent type of Cutaneous T-cell Lymphoma (CTCL). The other forms of cutaneous lymphoma include the CD30 positive lymphoproliferative disorders (CD30+ LPDs), subcutaneous panniculitis-like T-cell lymphoma, Primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma, Primary cutaneous gamma/delta T-cell lymphoma, Extranodal natural killer/T-cell lymphoma, nasal type, and others.

The World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC) Classification

Indolent Clinical Behavior Aggressive Clinical Behavior
Mycosis fungoides Sézary syndrome  
Subcutaneous panniculitis-like T-cell lymphoma Primary cutaneous CD8+ aggressive epidermotopic T-cell lymphoma  
Primary cutaneous CD4+ small/medium pleomorphic T-Cell lymphoma   Primary cutaneous gamma/delta T-cell lymphoma  
CD30+ Lymphproliferative Disorders Primary cutaneous anaplastic large cell lymphomaLymphomatoid papulosis   Extranodal natural killer/T-cell lymphoma, nasal type  

Epidemiology

According to the CmaxInsight, the total incident cases of Cutaneous T-cell lymphoma (CTCL) were calculated to be around 9,000 in 2018 in 7MM including the United States, EU5 countries (the United Kingdom, France, Italy, Spain, and Germany) and Japan. The United States accounts for the highest incident cases of 3,430  in 2018 followed by EU5 countries, and Japan According to the National Organization for Rare Disorders (NORD), the Cutaneous T-cell lymphoma (CTCL) affects males twice as often as females. The majority of the CTCL cases are diagnosed between the age-group of 40 to 60 years. Further, it is expected that the incident cases of the CTCL would increase over the forecasted period.

Market Size

According to the Cmaxinsight, the market size of Cutaneous T-cell Lymphoma (CTCL) is growing at a CAGR of 5.54% for the forecasted period 2018-2028 in 7MM including the United States, EU5 countries (the United Kingdom, France, Italy, Spain, and Germany) and Japan. The United States accounts for the highest market share of around 40% in 2018 followed by EU5 countries, and Japan. The market is dominated by the availability of topical therapies, including corticosteroids, retinoids, different chemotherapy regimens, and others. The market is driven by rising incident cases, the expected launch of emerging therapies, technological advancement, and improving healthcare facilities.

Competitive Analysis

The market is dominated by the availability of the marketed drugs such as Istodax (Celgene Corporation), Poteligeo (Kyowa Hakko Kirin Co. Ltd), Valchlor/ Ledaga (Actelion), Uvadex (Mallinckrodt Pharmaceuticals), Targretin (Eisai Co., Ltd.), and Zolinza (Merck Sharp & Dohme Corp), and others. The expected launch of emerging therapies such as Quisinostat (Janssen), Remetinostat (Medivir AB), denileukin diftitox (Eisai Co., Ltd) and others shall have a positive impact on the market.

The companies are entering into the mergers, acquisitions, collaborations and other activities for increasing their market penetration. In January 2020, the Almirall had entered into an option agreement to acquire Bioniz Therapeutics and to establish a broad research agreement to further expand its innovative pipeline in medical dermatology. This collaboration would allow Almirall to executes its strategy to develop and expand its R&D pipeline with new treatment modalities with the objective to address highly underserved diseases within oncodermatology and immunodermatology.

Impact of Coronavirus (COVID19) on India Pharmaceuticals

Impact of Coronavirus (COVID19) on India Pharmaceuticals

India is one of the largest providers of generic drugs worldwide. India pharmaceutical industry supplies approximately 50% of vaccines worldwide, 40% of generics in the United States and 25% of all medicines in the United Kingdom. India exports bulk drugs, intermediates, drug formulations, biologicals, Ayush & herbal products, and surgicals to various countries.

According to the India Brand Equity Foundation (IBEF), the Indian pharmaceutical sector had a market size of USD 33 Billion in 2017. India’s pharmaceutical exports had witnessed an increase from USD 19.14 Billion in 2019 to USD 17.27 billion in 2018.

The novel coronavirus (COVID-19) outbreak had a negative impact on the India pharmaceutical industry in the following ways:

  • India has restricted the export of several drugs such as paracetamol, antibiotics such as tinidazole and erythromycin, hormone progesterone, which is used in the contraceptive pill, and vitamins B12, B1 and B6. These drugs account for approximately 10% of all India’s pharmaceutical exports.
  • The Indian government have imposed limits on the export of 26 pharmaceutical ingredients
  • Indian pharmaceutical companies are now close to exhausting their supply of raw materials such as active pharmaceutical ingredients (APIs). Moreover, the inventories related to the pharmaceutical ingredients are running low.
  • Several pharmaceutical companies who have contracts with domestic clients and various state governments to supply medicines have been crippled, as manufacturing has come to a halt due to a shortage of raw materials from China
  • Pharmaceutical companies are not able to procure pharmaceutical ingredients for Mintelukast, used for asthma, pain medication Nimesulide, and Amoxicillin, Ofloxaicin, and Chloramphenicol, which are used to treat bacterial infections, and antibiotic Metronidazole
  • Small and medium companies have been most  affected as they depend on traders and keep lower inventory
  • There is a drastic increase of 20-30% in the prices of raw materials used in medicines like Amoxicillin and Paracetamol.
  • The pharmaceutical logistics is facing the difficulties in receiving the raw material from other parts of the country