As of May 2017, there were roughly 65 drug candidates in the pipeline for chronic obstructive pulmonary disease (COPD), according to a recently released analysis from P&S Market Research.
“For achieving better efficacy and fewer side effects, targeted therapy can potentially stop or slow down the disease process,” says Kundan Kumar, a manager and client partner for the market research firm.
Albert A. Rizzo, MD, senior medical advisor for the American Lung Association and section chief of pulmonary medicine at Christiana Care Health System in Newark, Delaware, says the increasing number of drugs in the pipeline to treat COPD is encouraging.
“Some of the new pipeline drugs are designed to improve airflow and have impact on improving patient symptoms (dyspnea), while others actually are addressing the underlying disease process by attacking and controlling airway inflammation,” Rizzo explains. “This is by way of inhibiting the effect of cells such as the eosinophils and blocking the effect of molecules (cytokines) that incite the underlying inflammation.”
Potential different drug formulations, “particularly the inhaled type, offer a range of delivery devices and frequencies that allow the physician to find the best fit for the individual patient,” Rizzo says. “It truly offers the physician and patient a form of personalized medicine to treat their airway disease.”
Rizzo notes that some pending drugs have shown to decrease the risk of patients having recurrent exacerbations. “The more these drugs can be made accessible and convenient to use, the more impact they will have on the overall cost of care, if they keep the COPD population from having these exacerbations,” he says. “We know that one exacerbation leads to the likelihood of more exacerbations and the progression of the disease process.”
However, the new “biologic” drugs that impact the airway inflammation “often come with a high monthly cost,” Rizzo cautions. “Therefore, this has to be weighed against the cost-savings of a healthcare organization by keeping these patients from recurrently being hospitalized.”
Specific drug developments to watch
The pipeline includes benralizumab (AstraZeneca), PT010 (AstraZeneca), revefenacin (Theravance Biopharma), Bevespi Aerosphere (AstraZeneca), mepolizumab (GlaxoSmithKline) and HCP1202 (Hanmi Pharmaceutical).
Kumar is most excited about the first three medications.
“AstraZeneca is manufacturing respiratory biologic benralizumab, which is currently in phase 3,” he says. “This drug candidate is a humanized, afucosylated monoclonal antibody that inhibits interleukin-5 receptor alpha, thereby reducing sputum and blood eosinophil counts by the enhancement of antibody dependent cell-mediated cytotoxic effects.”
Benralizumab is being developed to be administered by subcutaneous route. “The company is also planning for regulatory submission,” Kumar says.
Furthermore, in March 2017, AstraZeneca began collaborating with Kyowa Hakko Kirin Co. Ltd., “for the exclusive rights of benralizumab for the treatment of severe asthma and COPD in Asia,” Kumar says.
Budesonide + glycopyrronium + formoterol fumarate, also known as PT010, is the second potential drug candidate from AstraZeneca, which is also in Phase III. The triple-drug combination “acts as a long-acting muscarinic antagonist (LAMA) and as a long-acting beta-2 agonist (LABA),” Kumar explains.
AstraZeneca is using a cosuspension delivery technology platform for the development of PT010. “The technology uses lipid-based porous particles to create stable compositions with drug crystals in hydrofluoroalkane (HFA) propellants, and high-performance aerosols upon actuation,” Kumar says.
In June 2013, AstraZeneca acquired Pearl Therapeutics Inc. for the development of PT010.
The company intends to submit regulatory filings for COPD in Japan in 2018, followed by filings in the U.S., China, and the European Union in 2019.
The third drug, revefenacin, also known as TD4208, is in phase 3 as well. “It is a small molecule that acts as a long-acting LAMA,” Kumar says.
The company is collaborating with Mylan N.V. for the development and commercialization of revefenacin.
“The positive phase 3 results of 1,055 patients with COPD demonstrated that revefenacin was generally well tolerated, and no new safety issues were identified,” Kumar reports. “The drug also demonstrated statistically significant and clinically meaningful improvements over placebo in trough forced expiratory volume (FEV) in 1 second and in overall treatment effect on the trough after 12 weeks of dosing.”
Earlier results from two phase 2 studies also support revefenacin as a potential drug candidate, according to Kumar.