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Eisai Chief Medical Officer Stewart Geary On Clinical Trial Complexity

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Clinical trial costs are increasing, and there’s no clear sign that these increased costs are improving the clinical trials process.

Stewart Geary, the chief medical officer for Tokyo-based pharma company Eisai, believes that clinical trials are too complicated, in part because trials include too many measurements. Excessive measurements “make it difficult for companies to perform and difficult for the investigators,” and these measurements are contributing to increased clinical trial costs, Geary said in an interview while visiting Washington, DC as a speaker at a regulatory science conference.

Geary and Eisai’s leadership team are looking for ways to simplify trial design and reduce the burden of excessive testing during trials. “The industry accumulates more data in clinical development right now than we can use. All those tests cost money, and more importantly are a burden on the patients in trials and the investigators who are helping with clinical development.”

Streamlining clinical trials may start with reducing the list of entry and exclusion criteria for patients. Similarly, Stewart is looking for ways to simplify trials by reducing the amount of testing for each patient visit as well as reducing the number of trial modifications during clinical development, focusing on the critical data that needs to be collected.

As the industry looks for ways to improve clinical development, they are also looking for improvements in the way trials are designed. Adaptive or Bayesian design rethinks the way trials are done by applying different statistical tools to randomizing and tracking trial subjects.

In reality, regulators (and therefore companies) are reluctant to radically change the way trials are designed. The purpose of adaptive design is to be able to make mid-trial adjustments based on accumulating information, resulting in more efficient trials (i.e., shorter time or fewer patients) or more in-depth data. While appealing in principle, problems can arise when there are varying levels of comfort with the design between regulators and the drug company, according to Geary.

“If there’s any doubt about the trial and the regulator does not agree with the adaptive design in retrospect, you’ve just lost years of time and potentially millions of dollars in development.”

Because of this, companies can be risk-averse unless there’s significant assurance that the regulators will accept the trial design. “We hear regulators expressing interest in new designs, but it’s difficult to find good examples where there has been agreement about a dramatically new design that leads to shorter development,” Geary said.

Geary is also hopeful for regulatory changes outside of the United States that can help with global development. It’s becoming difficult to do clinical development exclusively in the U.S. due to the demands of enrolling enough patients for a study. As a result, companies attempt to conduct simultaneous development in several countries to support a clinical development program.

But Geary says the varying regulations in several countries makes it  almost impossible to conduct a trial along the same timelines as in the U.S. and Europe. In China, it can take up to two years to receive approval to start a clinical trial, compared to a few months in the U.S. or Europe. So while the U.S. and European sites will be ready to initiate trials, the China sites will have to wait more than a year before they receive approval to start a study.

Companies also face Phase IV, or post-marketing, requirements that vary by country. “We increasingly have to devote our budgets for clinical development to post-marketing commitments in U.S., Europe and Japan. These add significantly to the cost of maintaining the product on the market, and those are resources we cannot use to develop new compounds,” Geary said.

Eisai, like many drug companies, faces a problem of having more product candidates it would like to develop than it can find financial resources to use for development. To address this, Eisai is looking for ways to share risk with partners who can finance a portion of the trials.

For example, Eisai recently received FDA approval for thyroid cancer therapy Lenvima (lenvatinib), which was developed in partnership with SFJ Pharmaceuticals Group. The compound was discovered at Eisai’s labs, and the company developed the compound, but SFJ stepped in to wholly fund Phase III studies for the compound in return for royalties and milestone payments after the product is launched on the market.

Eisai also manages resource constraints by narrowing its therapeutic focus to two main areas: oncology and neurology. In neurology, Eisai is focused heavily on Alzheimer’s disease, in which the company has had success in the past with Alzheimer’s therapy Aricept (donepezil). Clinical trials for Alzheimer’s therapies are complex and long, but Eisai is committed from the top down due to the company’s history in this disease space.

In oncology, Eisai is focused on capitalizing on specific molecular mechanisms that can be shared across cancers, rather than focusing on specific indications such as lung cancer, breast cancer or prostate cancer. By focusing on molecular targets, the company can then put its focus on anticipating how clinical development programs need to be expand based on insight in the basic biology of the disease. In part, this means the company is trying to find markers of a drug’s efficacy that are more complex than oncology’s traditional measures of disease progression.

Eisai is facing an industry-wide challenge: understanding of diseases continues to increase, but so do clinical trial costs and complexities. As drug companies chase elusive disease targets, they are also seeking ways to improve the clinical trials process.  

[This article first appeared on Forbes MedidataVoice.]    

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