Drug development: a marathon not a sprint

Making advances in science is rarely a straightforward and linear process, and getting innovative therapies to the people who need them is no different. It takes time to build a body of evidence and behind every breakthrough there are a number of disappointments. It might surprise some to learn that the majority of experiments in research and development (R&D) don't actually work. It can often feel like the odds are against us, which is why the ability to treat each failure as feedback, and to use the learnings as fuel to adapt and improve our approach, is such an important aspect of our work in pRED.

At Roche we strive to design the right therapies for the people who need them, at the right time. Our cutting-edge R&D pipeline — including ophthalmic treatments — reflects our approach to innovation in the scientific discovery of new potential drug targets, personalised healthcare, molecular engineering, biomarkers and continuous drug delivery. However, ultimately, it takes 12 years on average for a molecule to become a medicine, and sometimes even longer. Taking a recent success in ophthalmology as an example, it was the culmination of over 15 years of efforts to launch a new medicine last year, offering people living with two of the leading causes of vision loss a new alternative to the anti-VEGF-only approach. It’s a long process that requires hours of work, countless experiments, and large teams of passionate and devoted scientists.?

However, it’s not all doom and gloom. The development journey is incredibly rewarding when, against the odds, the science comes together in a result that can really transform the lives of people living with ophthalmic conditions. Recently, my colleague Paulo Fontoura perfectly captured why our professional success can be such a personal highlight.?

From theory to practice?

So how do we do it??

At Roche pRED, we have a unique setup in that we have a dedicated ophthalmology group covering everything from initial ideas and drug development in the preclinical space, to clinical development and even biomarker development. In this way, we take a fully integrated approach that enables us to understand the needs of people living with ophthalmic conditions and develop medicines that meet those needs.

There are many steps in the Roche drug development process, and the ophthalmology pRED team is involved in the initial stages:

1. To start with, there are three things we must identify and understand: the unmet patient need, a potential molecule or pathway in the body that we can target and the therapeutic modality or technology we will use to target it. Usually, this is an iterative process that involves optimising potential drug molecules to get one with the profile we are looking for.?
2. Based on the drug molecule and the desired therapeutic effect, we then develop a biomarker strategy. This involves seeking answers to a number of clinical questions — such as ‘who are the people we hope will benefit from the treatment?’ —? enabling us to develop a robust clinical study.?
3. An important step is to test the safety profile of the drug molecule, which includes both in vitro (taking place outside of a living organism) and in vivo (taking place in a living organism) experiments, and ensure it does not cause any concerning side effects.??
4. We’re then ready to move into phase I clinical trials, which aim to demonstrate a potential treatment’s tolerability and safety in humans. In ophthalmology, this is often in people living with the target disease. We aim to observe initial efficacy or signals that the molecule is reaching the desired biomarker. The goal is to understand how the molecule interacts with the body and demonstrate that nothing unexpected happens. If a potential treatment is successful, it will progress to a phase II trial involving more people living with the condition we are trying to treat, to assess safety parameters as well as identify the best dose and treatment regimen.?

Phase III clinical trials follow, which aim to demonstrate the efficacy and safety of a potential treatment on a much larger scale. Only if all these different phases are successful, and following regulatory assessment and approval, can a medicine become available for the people it was designed for.

Current research goals and pipeline prospects

We have some really exciting ophthalmology molecules currently progressing through the drug development process. Currently, Roche has the broadest late-stage retina pipeline in the industry, including treatments for age-related macular degeneration, geographic atrophy, diabetic macular edema, diabetic retinopathy and retinal vein occlusion.?

In our clinical stage pipeline, a key focus is on targeting inflammation in retinal diseases and further increasing durability, so that people with these conditions can achieve even better vision gains than are currently possible, with fewer treatments, which in turn would reduce the treatment burden.?

Our early-stage pipeline also includes gene therapies and treatments for conditions affecting the anterior segment (front) of the eye. We've built up a very promising, industry-leading pipeline, and it remains a great privilege to have the resources to work on bringing the next generation of medicines to those living with vision loss.

To hear more about my thoughts on the future of eye care, take a look at another recent article I wrote here.?