Nicholas Gross

The COPD Pipeline XXXVII

From the GlaxoSmithKline trial of danirixin: “The inflammation associated with chronic obstructive pulmonary disease (COPD) is characterized by a prominent infiltration of neutrophils in lung tissue and airways. The CXC chemokine receptor type 2 (CXCR2) plays a pivotal role in neutrophil recruitment to the lungs resulting in progressive fibrosis, airway stenosis, and destruction of the lung parenchyma characteristic of COPD. There is a paucity of novel therapies that target these symptoms, and there are no currently available therapies that modify disease progression in COPD. Danirixin (GSK1325756) is a selective CXCR2 antagonist being developed as a potential anti-inflammatory agent for the treatment of COPD and influenza. This study is a mechanistic study which aims to evaluate the effect of danirixin in reducing neutrophil extracellular traps (NETs) or NETosis. Subjects will be randomized (3:1) to receive danirixin hydrobromide (HBr) 35mg orally twice daily or matching placebo for 14 days. Subjects may continue to use rescue medication(s) and inhaled COPD maintenance medication(s) during the study. The study will consist of a screening period of up to 30 days, a 2-week treatment period, and a 1-week follow-up visit via phone call.”1

The COPD Pipeline XXXIV

Inevitably, we are interested in the industry with which we interact every day. A very short report of its state is of interest (a more detailed report can be found elsewhere1). Among the top 15 pharmaceutical companies, overall Research and Development (R&D) spending worldwide remains consistent at a collective total of about

The COPD Pipeline XXXV

70 billion a year. In order of annual revenue (for 2015), Roche was at the top for R&D, followed in order by Johnson and Johnson, Novartis, Pfizer, Merck, Bristol-Myers Squibb, AstraZeneca, Sanofi, Eli Lilly, GlaxoSmithKline, AbbVie, Amgen, Celgene and Takeda.1 R&D spending by the top 3 is close to each other, each being about

The COPD Pipeline XXXVI

9 billion per year; the last 3 are about

The COPD Pipeline XXXIII

3 billion each. As a percentage of overall revenue, the proportion of investment in R&D is around a disappointing 15%-20% for most pharmas, the exceptions being Bristol-Myers at 36% and Celgene at 40%. For us pulmonologists, one looks to Novartis (near the top), and AstraZeneca and GlaxoSmithKline (middle of the pack). Looking to the future is difficult because much of the really innovative work is done by small companies which belong to the “big boys” and that will only be brought into the major company when and if the small companies show some real promise, a strategy that protects the shares of the major players. Adipose-Derived Cellular Stromal Vascular Fraction (AD-cSVF)

The COPD Pipeline, 2004-2014

Dealmakers in biopharma ended April with much disappointment and grumbling. This was the year that Mergers and Acquisitions were supposed to take off, with a new president bullishly asserting plans to reform taxes in a way that would free up billions in “big pharma” cash held overseas. As one trade journal states: “Didn’t happen. Donald Trump is so far bogged down on Obamacare reform and not able to deliver a much-ballyhooed tax reform pledge — for now.”1 Most people are disappointed with the pace of mergers and acquisitions. In the first quarter, pharmaceutical dealmakers were down 13% compared to the same period a year ago.1

Nebulized Long-Acting Beta2-Agonists: More Than Just Bridging Gaps in the Management of Symptomatic COPD

Contract Pharma is a publication that reviews, among other things, the pharmaceutical industry annually. Those of us who work in chronic obstructive pulmonary disease (COPD) take an interest in the source of the drugs we use and Contract Pharma brings that information to us. Each year they report the status of the top 25 pharmaceutical companies.1 For each pharma, a report lists the newly approved drugs, those pending approval, drugs in phase 2, those in early research, drugs coming off patent, and some other less interesting data. There is usually a tussle between Pfizer and Novartis for the top. For the 2017 report (which is based on 2016 sales) Pfizer, Inc., is number 1. As I sift through the top 25 pharma companies, I look for drugs that might be the ones we will one day be prescribing for our patients with COPD. Pfizer has no new COPD drugs anywhere in the process of development unless one includes Prevnar 13 which was just approved. Next is Novartis which has Fevipiprant, an interesting CRTh2 antagonist in phase 1. But it is for an asthma indication. Merck, at number 3, has MK-1029, also a CRTh2 antagonist, but also in trials as a potential asthma therapy. Merck has no agents in development for COPD. Nor, going down the list, has Roche. GlaxoSmithKline has Relvar Elipta (recently approved), a triple for COPD that is pending the Food and Drug Administration’s (FDA’s) review, and mepolizumab for COPD. Next on the list are Sanofi, Johnson & Johnson, Gilead, and ABBVie with no COPD drugs. Then AstraZeneca with Bevespi/Aerosphere and benralizumab both in phase 2 for a COPD indication. Teva has several drugs for asthma but none for COPD. Next on the list are Lilly, Bristol-Myers Squibb, and Bayer. Finally, Boehringer Ingelheim has worked with Hamni Pharmaceuticals on HCP1202 for COPD. It is in a Phase 2 trial. Then, moving down the list, comes a desert with no potential COPD drugs, Novo Nordisk, Merck KGAA, Takeda, Allergan, Biogen, Shire, and Celgene. Mylan brings the list to a close with its revefenacin, a nebulized long-acting muscarinic antagonist (LAMA) in phase 3. The point here is that the third largest cause of death in most of the world needs more novel therapies. Other than the me-too’s, we have just 2 ‘-lizumabs’ in the works for COPD. Cancer, heart, and diseases of ageing are all well represented in late stage development, which is appropriate. But COPD should be up there with them. Autologous bronchial basal cells transplantation is The COPD Pipeline XXXVI Nicholas Gross, MD, PhD1