The Advantages of Structure-Based Drug Design in Biopharmaceutical Discovery and Development

drug design
The failure of new drug candidates to live up to expectations can be disappointing when discovery and development requires companies to invest time and money. Can structure-based drug design lower the rate of failure?
Image source: Flickr CC user e-Magine Art

Developing a new drug requires that life sciences companies invest vast amounts of resources. Depending on the complexity of treatment, firms can devote over a decade to the R&D process. In terms of financial cost, a single drug can require hundreds of millions of dollars from start to finish. Considering how much time and money is involved, is it little wonder that organizations are keen on seeing their efforts recouped?

Unfortunately, that end goal appears to be getting more difficult. Recent estimates claim that the cost of creating a new drug approximately doubles every nine years. This wouldn’t pose a problem if drug approvals consistently kept up with that pace. Only recently has the FDA increased the number of biologics approvals with 11 in 2014 and 12 in 2015. While we can certainly hope this trend will continue, the current political climate may complicate matters, sending us back to the time period when biologics approvals averaged only 6 per year.1 A closer look reveals why approval rate has historically lagged behind the rate of rising costs: the failure rate of late stage clinical trials, which are considered by many to be the end of the R&D process. When a promising drug candidate fails to live up to expectations at this critical point, the money invested in the project is lost.

Let’s consider the case of solanezumab, a monoclonal antibody drug intended to treat Alzheimer’s disease. Initially hailed as a breakthrough in treating the neurodegenerative condition, the reality didn’t live up to the claims. In fact, despite showing that its usage slowed cognitive decline in some patients, the drug failed to meet the primary aims of two major clinical trials.2 Even with the mixed results, the inability to meet the intended endpoints severely impacted solanezumab’s chances of garnering FDA approval.3 In such cases as this, companies aren’t left with many options. They can abandon years of research and development, they can continue with more studies in the hopes that pursuing small signs of benefit will yield enough success to overcome the shadow of past failures, or they determine whether the drug can be used for other treatment applications. No matter what choice organizations make, however, the end result is that they will have to face financial repercussions—whether in the form of actual loss or requiring more capital investment.

The Argument for Using Structure-Based Drug Design in Biologics Development

Despite the difficulties, life sciences companies cannot stop innovating and developing new drugs. Many diseases have yet to receive a cure—such as the case with Alzheimer’s, which currently has drugs that treat only its symptoms, not its underlying cause. Since these remaining “cureless” diseases are notoriously complicated in terms of mechanism and manifestation, it only makes sense that we turn toward biotherapeutics as a potential answer.

But as the biologics field grows more crowded—doubly so with the emergence of biosimilars—life sciences companies will need to find ways to retain their competitive edge. One idea they can adopt is to streamline their workflow strategies. Not only would this maximize efficiency, it would also address the problem presented by rising costs of the R&D process. To streamline the process further, structure-based drug design can serve as the cornerstone for this strategy.

To increase the likelihood of success, companies can focus on designing candidate drugs with high-binding affinities to a biological target. Doing so would, of course, require the structural knowledge of the intended target, but by utilizing this type of direct drug design, organizations can minimize inefficiencies during the discovery phase. For example, laboratories can identify whether a candidate drug shows promise in treating a specific disease earlier in the R&D cycle. If it’s determined that a potential biotherapeutic shows low-binding affinity to a target, they can eliminate that candidate drug from their pool of options long before ever reaching the clinical trial stage. If they can utilize a 3D modeling environment, they can even discern this fact before the assay stage, which would further save on research dollars.

Focusing on structure-based design has other advantages as well. By having the ability to visualize 3D structures, researchers can screen more candidate drugs efficiently. It speeds up the development cycle, allowing them to bring the most promising ones to light faster. Not only can organizations screen for biotherapeutics targeting a specific disease, they can determine early on whether these therapies might have other applications. They then have the option to develop therapies with the potential to treat multiple disorders, which would diversify their catalog and protect their market edge should they prove successful on all fronts.

Focusing on structure during the drug design phase doesn’t only aid the screening process either. It can help later stages of the development process, too. For example, by modeling potential 3D structures, researchers can predict behaviors. Typically, this is most useful in determining binding affinity, but it can be used to ascertain any potential downstream issues. A biotherapeutic may be extremely promising in theory, but in reality may have problems during the isolation and purification stages that could affect manufacturing capacity. Armed with this information, firms can decide not to pursue the opportunity due to the difficulties involved and their associated costs.

As the biologics field grows more competitive, life sciences firms will need to adopt strategies to keep R&D costs down while increasing their chances of gaining marketing approval. The BIOVIA Biologics Solution supports biotherapeutics companies in their structure-based drug design efforts. Its many features enable users to analyze DNA and protein sequence information effectively, assess antibody candidates and utilize 3D structure modeling to predict physical properties and determine ways to optimize developability. Please contact us today to learn more.

  1. “New Drugs at FDA: CDER’s New Molecular Entities and New Therapeutic Biological Products,” Last updated 1/13/16,
  2. “Lilly Treatment Slows Alzheimer’s Course in Some Patients,” August 24, 2012,
  3. “Eli Lilly’s solanezumab faces grim prospects of attaining conditional FDA approval in mild Alzheimer’s,” September 4, 2012,

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