Amgen, Novartis, Astellas, and GlaxoSmithKline Lead Pipeline News
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A roundup of the latest market developments from the pipelines of the pharmaceutical majors and other related news, featuring news from Eli Lilly and Company, Amgen, Novartis, and GlaxoSmithKline.

Editor’s Note: This article was updated on a continuous basis for news announced from Wednesday, July 19, 2017 to Tuesday, July 25, 2017.

Lilly, Incyte in Late-Stage Setback for Arthritis Drug
Eli Lilly and Company and Incyte, a biopharmaceutical company, report that the resubmission of their new drug application (NDA) to the US Food and Drug Administration (FDA) for baricitinib, a drug to treat moderate-to-severe rheumatoid arthritis (RA), will be delayed beyond 2017.

This is the second recent setback for baricitinib which has been touted by some analysts as a potential blockbuster drug. In April 2017, the companies received a Complete Response Letter (CRL) from the FDA seeking additional clinical data to determine the most appropriate doses of the drug and to further characterize safety concerns across treatment arms. Lilly and Incyte submitted the NDA for baricitinib to the FDA in January 2016, and in January 2017 announced that the FDA had provided a three-month extension to allow time for review of additional data analyses.

Baricitinib is a Janus kinase (JAK) inhibitor currently in clinical studies for treating inflammatory and autoimmune diseases. It was approved in the European Union in February 2017 for treating moderate-to-severe active rheumatoid arthritis. Prior to the CRL, the drug was projected for blockbuster status by 2021 with forecast sales of nearly $1.3 billion, according to estimates from Clarivate Analytics.

The companies will be further discussing the path forward with the FDA and are evaluating options for resubmission, including the potential for an additional clinical study, as requested by the FDA. The length of time to a resubmission for the NDA will depend on which option the companies pursue and further FDA discussions, but itmis anticipated to be a minimum of 18 months.

The FDA has indicated that a new clinical study is necessary for a resubmission in order to further characterize the benefit/risk across doses, in light of the observed imbalance in thromboembolic events that occurred during the placebo-controlled period of the RA clinical program. This request for an additional clinical study does not impact the ongoing clinical trials for baricitinib.

In the European Union, where baricitinib 2-mg and 4-mg tablets have been approved since February 2017, the European Medicines Agency’s advisory committee recently agreed to update the label with a precaution for patients who have risk factors for deep venous thrombosis and pulmonary embolism. In Japan, where baricitinib was also recently approved, the label includes a similar precaution. Baricitinib is also approved in Kuwait and Switzerland.

In December 2009, Lilly and Incyte announced an exclusive worldwide license and collaboration agreement for the development and commercialization of baricitinib and certain follow-on compounds for patients with inflammatory and autoimmune diseases.

The drug is also being studied in Phase II trials for atopic dermatitis and systemic lupus erythematosus. The Phase III trial for psoriatic arthritis has been delayed and will not begin in 2017 as previously expected.

Source: Eli Lilly and Company


FDA Accepts Amgen, Novartis BLA For Migraine Drug
The US Food and Drug Administration (FDA) has accepted for review the biologics license application (BLA) for Amgen’s Aimovig (erenumab) for the prevention of migraine in patients experiencing four or more migraine days per month. Aimovig is a monoclonal antibody targeting the calcitonin gene-related peptide receptor, specifically designed for the prevention of migraine.

The FDA has set a Prescription Drug User Fee Act target action date of May 17, 2018. If approved, Aimovig will be jointly commercialized in the US by Amgen and Novartis.

In August 2015, Amgen entered into a global collaboration with Novartis to jointly develop and commercialize treatments in the fields of migraine and Alzheimer’s disease (AD). The collaboration focuses on investigational Amgen drugs in the migraine field, including Aimovig and AMG 301, currently in Phase I development. In April 2017, the collaboration was expanded to include co-commercialization of Aimovig in the US. For the migraine program, Amgen retains exclusive rights in Japan, and Novartis has exclusive rights in Europe, Canada, and rest of world. Also, the companies are collaborating in the development and commercialization of a beta-secretase 1 inhibitor program in AD.

Source: Amgen


FDA Grants Orphan-Drug Designation to Astellas’ Leukemia Drug
The US Food and Drug Administration (FDA) has granted orphan-drug designation to Astellas’ gilteritinib for treating acute myeloid leukemia. The drug is in Phase III development.

Gilteritinib is a receptor tyrosine kinase inhibitor of FLT3 and AXL, which are involved in the growth of cancer cells. Gilteritinib has demonstrated inhibitory activity against FLT3 internal tandem duplication as well as tyrosine kinase domain, two common types of FLT3 mutations, according to information from Astellas.

Source: Astellas


GSK Submits Regulatory Filing for Pediatric Use for Asthma Drug
GlaxoSmithKline (GSK) has announced the filing of a supplementary new drug application (sNDA) to the US Food and Drug Administration (FDA) for the use of Arnuity Ellipta (fluticasone furoate 100 mcg and 200 mcg) as maintenance treatment of asthma as prophylactic therapy in children aged 5 to 11 years (inclusive). The sNDA is seeking approval for a dose of 50-mcg once-daily, delivered using the Ellipta inhaler in this group of patients.

Arnuity Ellipta is an inhaled corticosteroid that was approved in the US in August 2014 for the maintenance treatment of asthma in patients aged 12 years and older.

Fluticasone furoate, the active ingredient in Ellipta, is also the active ingredient in GSK’s nasal spray, Veramyst, which was approved by the FDA in 2007 to treat symptoms of seasonal and perennial allergic rhinitis in patients two years of age and older.

Source: GlaxoSmithKline


EMA Advisory Committee Recommends 10 Drugs for Approval
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended for approval 10 drugs as outlined below:

  • Roche’s Tecentriq (atezolizumab) as a monotherapy for treating adults with locally advanced or metastatic non-small cell lung cancer after they have been previously treated with chemotherapy. The CHMP has also adopted a positive opinion for the use of Tecentriq as a monotherapy for treating adults with locally advanced or metastatic urothelial carcinoma (a form a bladder cancer), who have been previously treated with a platinum -based chemotherapy or who are considered ineligible for cisplatin chemotherapy.

Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7 receptors. By inhibiting PD-L1, the drug may enable the activation of T cells.  It has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines, and various chemotherapies across a broad range of cancers, according to information from Roche.

Source: Roche

  • Roche’s Gazyvaro (obinutuzumab) in combination with chemotherapy, followed by Gazyvaro maintenance in people achieving a response, as a new treatment option for previously untreated advanced follicular lymphoma.

Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system, according to information from Roche.

Gazyvaro is marketed as Gazyva outside the European Union and Switzerland. Gazyva/Gazyvaro is currently approved in more than 80 countries in combination with chlorambucil, for people with previously untreated chronic lymphocytic leukaemia and in combination with bendamustine for people with certain types of previously treated follicular lymphoma.

Source: Roche

  • Roche’s Actemra/RoActemra (tocilizumab) for the treatment of giant cell arteritis (GCA) a chronic and potentially life-threatening autoimmune condition. Actemra / RoActemra was approved for the treatment of GCA by the US Food and Drug Administration (FDA) in May 2017.

Actemra / RoActemra is an approved anti-IL-6 receptor biologic available in both intravenous and subcutaneous formulations for the treatment of adult patients with moderate-to- severe active rheumatoid arthritis.

              Source: Roche

  • Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide [D/C/F/TAF]), a once-daily darunavir-based single-tablet regimen by Johnson & Johnson’s Janssen-Cilag International NV for human immunodeficiency virus type 1 (HIV-1) infection in adults and adolescents aged 12 years and older with body weight of at least 40 kg, with genotypic testing guiding use.

In December 2014, Janssen and Gilead Sciences amended a licensing agreement for the development and commercialization of a once-daily STR combination of darunavir and Gilead’s TAF, emtricitabine, and cobicistat. Under the agreement, Janssen and its affiliates are responsible for the manufacturing, registration, distribution and commercialization of this STR worldwide.

Source: Janssen

  • Merck & Co.’s Keytruda (pembrolizumab), an anti-PD-1 therapy, for treating certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer. Specifically, Keytruda is recommended for treating locally advanced or metastatic urothelial carcinoma in adult patients who have received prior platinum-containing chemotherapy as well as adult patients who are not eligible for cisplatin-containing chemotherapy.

Keytruda is Merck & Co.’s blockbuster immuno-oncology therapy with 2016 global sales of $1.4 billion.It is indicated for treating multiple cancers. In the US, the drug is approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma, a common form of bladder cancer, who are ineligible for cisplatin-containing chemotherapy. Keytruda is also approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Keytruda is also approved in the US for treating unresectable or metastatic melanoma, metastatic non-small cell lung cancer, recurrent or metastatic head and neck squamous cell carcinoma, and refractory classical Hodgkin lymphoma.

              Source: Merck & Co.  

  • Sanofi’s Dupixent (dupilumab),for use in adults with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy.

Dupixent is a human monoclonal antibody designed to specifically inhibit overactive signaling of two proteins, interleukin-4 and interleukin-13, believed to be drivers of the persistent underlying inflammation in AD, according to Sanofi.

In the US, Dupixent is approved for treating adults with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. Dupixent can be used with or without topical corticosteroids.

              Source: Sanofi

  • AbbVie’s Humira (adalimumab) for treating chronic non-infectious anterior uveitis in pediatric patients from two years of age who have had an inadequate response to or are intolerant to conventional therapy, or in whom conventional therapy is inappropriate.

Humira is AbbVie’s top-selling drug with 2016 global sales of $16 billion. It is approved for multiple indications:for use in adults with moderate-to-severe active and progressive rheumatoid arthritis, severe active ankylosing spondylitis (AS), severe axial spondyloarthritis without radiographic evidence of AS, moderate-to-severe chronic plaque psoriasis, active and progressive psoriatic arthritis, moderately to severely active Crohn’s disease, moderately to severely active ulcerative colitis, and non-infectious intermediate, posterior and panuveitis in adults.

Source: Abbvie

  • Merck KGaA’s Bavencio (avelumab) as a monotherapy for treating adult patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer.

Avelumab is a human antibody specific for a protein called PD-L1, or programmed death ligand-1. Avelumab is designed to potentially engage both the adaptive and innate immune systems. The European Commission will now review the CHMP’s recommendation, with a decision expected in the third quarter of 2017.

Avelumab, initially discovered and developed by Merck KGaA, is part of the immunotherapy alliance that Pfizer and Merck KGaA formed in November 2014 under which the companies will collaborate on up to 20 high priority immuno-oncology clinical development programs, including combination trials.

The US Food and Drug Administration granted accelerated approval for avelumab in March 2017 for treating mMCC in adults and pediatric patients 12 years and older; and in May 2017 for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy therapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

 Source: Merck KGaA and Pfizer

  • Bayer’s Xarelto (rivaroxaban) in combination with single antiplatelet therapy for treating patients with atrial fibrillation requiring oral anticoagulation and undergoing percutaneous coronary intervention with stent placement.

Xarelto is approved for seven indications, including: the prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors; the treatment of pulmonary embolism (PE) in adults; the treatment of deep vein thrombosis (DVT) in adults; the prevention of recurrent PE and DVT in adults; the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip replacement surgery; the prevention of VTE in adult patients undergoing elective knee replacement surgery; and the prevention of atherothrombotic events (cardiovascular death, myocardial infarction or stroke) after an acute coronary syndrome in adult patients with elevated cardiac biomarkers and no prior stroke or transient ischaemic attack when co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine.

While licenses may differ from country to country, across all indications Xarelto is approved in more than 130 countries.

Source: Bayer

  • Novartis’ Rydapt (midostaurin) for treating adults with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive. If approvied, Rydapt will be indicated in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy, and for patients in complete response, followed by Rydapt single- agent maintenance therapy, for adult patients with newly diagnosed AML who are FLT3 mutation-positive. Rydapt was also recommended for approval as a monotherapy for treating adult patients with aggressive systemic mastocytosis, systemic mastocytosis with associated hematological neoplasm or mast cell leukemia.

Rydapt is an oral, multi-targeted inhibitor of multiple kinases, including FLT3 and KIT, which help regulate many essential cell processes, interrupting cancer cells’ ability to grow and multiply, according to information from Novartis.

In the US, Rydapt is FDA-approved for treating adults with newly diagnosed AML who are FMS-like tyrosine kinase 3 mutation-positive (FLT3+) as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy.

Source: Novartis

Editor’s Note: This story was updated on July 27, 2017 to include additional information on avelumab.

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