Developing an inhalable drug for hard-to-treat asthma

4 minute read

Internal architecture of the trachea and lungs, 3D printed in Frosted Ultra Detail plastic

Pieris Pharmaceuticals’ drug, which was developed in collaboration with University of Melbourne researchers, has successfully completed Phase I clinical trials.

Key points

  • An inhalable drug based on anticalin technology has been designed by Pieris Pharmaceuticals in collaboration with the University of Melbourne.
  • The drug is designed to suppress the immune response that causes severe forms of asthma, which often do not respond to current treatments.
  • AstraZeneca has reached an agreement with Pieris Pharmaceuticals to complete the testing and regulatory steps needed to bring the drug to market.

The outcome

An inhalable drug for treating moderate and severe asthma has successfully completed Phase I clinical trials. It is scheduled to undergo Phase II clinical trials in the near future. (Phase I trials test the safety of a new drug, while Phase II trials test whether it has the intended effects.)

The drug (PRS-060/AZD1402) was developed by international biotechnology company Pieris Pharmaceuticals in collaboration with the University of Melbourne. PRS-060/AZD1402 is designed to suppress the immune response that causes severe and hard-to-treat asthma.

In 2017, global biopharmaceutical company AstraZeneca reached an agreement with Pieris to license the drug and complete the testing and regulatory steps necessary for marketing it to consumers.

The need

Asthma inhalers (which administer beta-agonists or steroids) ease the symptoms of asthma. But these treatments are less effective in people who have severe asthma or develop steroid-resistant asthma.

More than 300 million people live with asthma. It is the most common chronic disease in children. As many as 250 000 asthma deaths are reported worldwide each year.

Estimates of the prevalence of severe asthma vary from less than 1 per cent of people with asthma to over 20 per cent. A study combining data from 11 countries showed that people with severe asthma cost the healthcare system around 30 per cent more than those with mild or moderate asthma.

Modern drug treatments have helped to reduce the disease burden for people with asthma – measured in number of years lost due to ill health, disability or early death per 100 000 population – by 36 per cent since 1990. But people with the most severe and poorly controllable forms of asthma need more drug options.

The research

In some cases, the inflammatory response in asthma becomes overwhelming and no longer responds to available drugs. A key reason for this is the overactivation of an immune response called T2 immunity. This overactivation occurs in about half of the cases of severe or steroid-resistant asthma.

In the 1990s, Professor Gary Anderson from the Lung Health Research Centre at the University of Melbourne and colleagues discovered the molecule responsible for this overactivation: interleukin 4 (IL-4). IL-4 and a closely related interleukin, IL-13, bind to IL4Ra, a receptor molecule on the surface of cells in the airways. This induces T2 immunity and inflammation.

The discovery created a new target for drug development. The pharmaceutical industry developed antibodies to block IL-4’s and and IL-13's access to IL4Ra, thus limiting the T2 immune response.

Although this strategy was effective, antibodies are not ideal for asthma patients. These large molecules are expensive to make and can be given to patients only via injection. They do not easily reach the surface cells of the lung airways. As a result, antibody treatments were reserved for the most severe and hard-to-treat asthma cases.

Professor Anderson recognised that an inhalable molecule would reach the lungs more quickly and efficiently than an injectable drug.

Technology development history

In the 2000s, Pieris Pharmaceuticals began investigating the therapeutic potential of lipocalins – proteins found in the lungs and human tears. The company created billions of variants of the lipocalin molecular structure, each of which could be a potential new drug.

In 2010, Pieris Pharmaceuticals partnered with a University of Melbourne research team led by Professor Anderson. The research team tested the lipocalin variants for their ability to bind and block IL4Ra.

The team identified a lipocalin with the desired properties in 2012 and named it PRS-060.

Learn more about how the drug works

Since both the inhalable lipocalin and injectable antibody work in a similar way, this new class of drugs are called anticalins. They are produced using Pieris Pharmaceuticals’ proprietary Anticalin® technology.

To develop PRS-060 for clinical use, Pieris Pharmaceuticals set up an Australian subsidiary in 2014.

The team undertook preclinical technical development and safety studies of PRS-060 between 2013 and 2016. They used funding from a 2015 NHMRC Development Grant of over $A550 000.

In 2019, the team completed a Phase Ia and Ib clinical trial in Australia. They showed that PRS-060 was safe to use, well tolerated and sufficiently bioavailable in people with mild asthma.

AstraZeneca reached a licensing agreement with Pieris Pharmaceuticals in 2017 to commercialise the drug, now called PRS-060/AZD1402. Under the terms of the agreement, which covers five anticalins, AstraZeneca will give Pieris Pharmaceuticals upfront and near-term milestone payments of $US57.5 million, development-dependent payments of up to $US2.1 billion, and royalties on sales of any commercial products.

Following the success of the Phase Ia and Ib trials, AstraZeneca is scheduling multicentre Phase II clinical trials of PRS-060/AZD1402 to begin in the near future.

Pieris Pharmaceuticals and the University of Melbourne are investigating the potential use of Anticalin® technology in other lung diseases, including cancer.

Partners

Pieris Pharmaceuticals
AstraZeneca

Funding support

NHMRC Development Grant (109338)

Publications

Bruns I et al (2019) Phase 1 evaluation of the inhaled IL-4Ra antagonist, AZD1402/PRS-060, a potent and selective blocker of IL-4Ra. European Respiratory Journal 54: OA5336. doi: 10.1183/13993003.congress-2019.OA5336

Anderson GP et al (2015) Discovery of PRS-060, an inhalable CD123/IL4Ra/TH2 blocking anti-asthmatic anticalin protein re-engineered from endogenous lipocalin-1. European Respiratory Journal 46: OA3256. doi: 10.1183/13993003.congress-2015.OA3256

Coyle AJ et al (1995) Interleukin-4 is required for the induction of lung Th2 mucosal immunity. American Journal of Respiratory Cell and Molecular Biology 13: 54–59. doi: 10.1165/ajrcmb.13.1.7598937

Image: Dave Farnham (CC BY 4.0)

People

Professor Gary Anderson
Dr Joe Ciccotosto
Dr Andrew Jarnicki
Dr Robert O’Donoghue

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