Phargentis has entered the clinical development phase for its second generic inhalation product – the COPD therapy containing indacaterol/glycopyrronium (85 mcg and 43 mcg) - today marketed by Novartis as Ultibro®Breezhaler®. This directly follows the company’s announcement of the first European sales of its generic Tiotropium bromide 18 µg Dry Powder Inhaler, the generic version of blockbuster COPD treatment Spiriva®Handihaler®.
During clinical development Phargentis will cooperate with the same CRO organization it worked with on its Tiotropium product. The clinical development phase started with pharmacokinetic (PK) studies. Firstly, a routine pilot PK phases intended to understand the in vivo variability of the development candidates as well as of the reference product, to confirm safety and tolerability of the developed formulations and device, and, finally, to enable the selection of the best candidate for further development stages. Secondly, the pivotal PK phase will follow, which will test, establish and finalize bioequivalence. The pivotal phase for the new product is expected to take place during H2 2022, with EU filing in H1 2023.
Phargentis is already progressing well in its pilot PK program, dosing has been completed successfully in all the subjects without adverse events. The study was performed with development candidates already manufactured at commercial scale to assure full representativeness of the product and to expedite the subsequent stages of the project. For this type of complex product, the use in clinical studies of material already manufactured at commercial scale is key to controlling the risks linked to the scale up.
What’s so special about clinical development for inhaled generics?
The clinical development process for inhaled generic products with their own inhaler device is particularly complex. Bioequivalence and interchangeability must be proven not only for the strength and delivered dose of the active ingredient, but also for the design, handling and performance of the new inhaler device.
Mitigating risk from before day one
Phargentis’ Early Market Entry development strategy is a risk-mitigation based approach, designed specifically to identify and mitigate risks even before development begins. The risk mitigation strategy examines each aspect of the development and industrialization of the product. Initially the company analyses the existing patent constraints in meticulous detail, before selecting the most achievable, high-potential opportunities for development. Then, the Phargentis team evaluates technical, regulatory and market frameworks and implements comprehensive risk mitigation measures. In the risk mitigation process, continuous dialogue with the regulatory authorities is key to assuring a smooth development and approval pathway. Several scientific advice meetings are organized with the national authorities of the targeted markets to collect the most comprehensive and helpful feedback even before the pivotal clinical development phase begins.
What is the new indacaterol/glycopyrronium therapy?
indacaterol/glycopyrronium combination therapy is a fixed-dose bronchodilator for managing moderate to severe COPD. The most common market version of it is Ultibro® Breezhaler® which contains two active substances: indacaterol (85 mcg), a long-acting beta-2 agonist causing the muscles of the airways to relax, and glycopyrronium (43 mcg) a muscarinic-receptor antagonist which blocks the muscarinic receptors which control the contraction of muscles during inhalation. The therapy is designed to be taken once daily, at the same time each day, in its DPI device. Each capsule is a single dose.
The treatment relieves COPD symptoms (improving patients’ Forced Expiratory Volumes (FEV) and reducing flare-ups or exacerbations) (1). It has also been found to significantly boost lung and cardiac function in COPD patients with lung hyperinflation, a common occurrence in COPD linked to impaired cardiac function and worsening symptoms, particularly breathlessness. (2)
Phargentis CEO Andrea Tam announced: “Entering the clinical phase of development in our second generic inhalation treatment is a major milestone for us and a huge success for the team. This is such a highly valued and effective treatment, delivering positive benefits to patients and society, maintaining lives and outcomes whilst reducing healthcare and social costs. Once again, our Early Market Entry strategy allows us to move ahead confidently and safely. We look forward to the next important stage of this journey.”
Phargentis has a portfolio of three Active Development Programs (including Tiotropium bromide DPI and indacaterol/glycopyrronium and capsule DPI) that together address a market value exceeding 3.5b USD.