Investigational treatments in phase I and II clinical trials: a systematic review in chronic obstructive pulmonary disease (COPD)

ABSTRACT

Introduction. The current pharmacological treatments for the management of stable COPD permit the reduction of symptoms and frequency and severity of exacerbations, and the improvement of exercise tolerance and health status. However, they do not modify the long-term decline in lung function and patient health. Consequently, there is the strong need for ‘highly innovative’ medications that are focused on new targets and/or mechanisms for the treatment of COPD.

Areas covered. This systematic review assesses investigational agents in Phase I and II clinical trials over the last six years. It offers insights on whether drugs and/or formulations in clinical development offer future effective treatments of COPD.

Expert opinion. There is no evidence to suggest that current investigational agents can reduce lung function decline and cure COPD. However, looking forward, investigational, innovative treatments in combination with the therapies already recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) may provide future suitable tools to counteract the progression of COPD.

KEYWORDS:

• Investigational drugs
• phase I
• phase II
• copd outcomes
• efficacy
• safety
• pharmacokinetic
• copd treatment
• chronic obstructive pulmonary disease

Article highlights

• The established pharmacological management of stable COPD is based on the use of inhaled bronchodilators and corticosteroids. However, these approaches treat the symptoms, not the disease.

• A cure for COPD or the modification of the long-term decline in lung function has not been achieved.

• Bifunctional molecules such as MABAs and dual PDE3/4 inhibitors have the potential to tackle the therapeutic gap because of their beneficial effect on lung function.

• Novel anti-inflammatory agents such as CXCR2 antagonists, PI3Kδ and p38 MAPK inhibitors are under investigation.

• Trough forced expiratory volume in 1 second (FEV₁) is not the most relevant endpoint for testing investigational anti-inflammatory drugs, especially on a short-term basis. Hence, other efficacy endpoints should be considered for future clinical trials.

• Those drugs under investigation may not deliver the ultimate disease-modifying agent, but they could synergistically interact with recommended therapeutic options and provide further suitable tools to treat the progression of COPD.

This box summarizes key points contained in the article.

Declaration of interest

L Calzetta has participated as an advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis, received non-financial support from AstraZeneca, a research grant partially funded by Chiesi Farmaceutici, Boehringer Ingelheim, Novartis and Almirall, and is or has been a consultant to ABC Farmaceutici, Recipharm, Zambon, Verona Pharma and Ockham Biotech. His department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis and Zambon. MG Matera has participated as a lecturer and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline and Novartis, and has been a consultant to ABC Farmaceutici, Chiesi Farmaceutici. Her department was funded by Novartis. M Cazzola has participated as a faculty member, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Verona Pharma, and Zambon, and is or has been a consultant to ABC Farmaceutici, AstraZeneca, Chiesi Farmaceutici, Edmond Pharma, Lallemand, Novartis, Ockham Biotech, Verona Pharma, and Zambon. His department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. P Rogliani participated as a lecturer and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma and Novartis. Her department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis and Zambon. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer has participated in consulting, advisory boards, speaker panels, or received travel reimbursement for Amphastar, Astra Zeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Mylan, Novartis, Oriel, Pearl, Sunovion, Teva and Theravance. They have conducted multicenter clinical research trials for approximately forty pharmaceutical companies. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.