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Exclusive Life Science Feature trolled trial is not very appealing for someone seeking real therapeutic benefits. Garnett admits in early phases it is difficult to avoid the placebo problem. Though it can't always be eliminated, it can be mitigated through modeling via new statistical approaches. "These models allow you to create a very large virtual placebo group so the actual placebo group can be small." Garnett believes improving communication with participants can also be helpful — especially when you consider the likelihood of increased reliance on patient-reported outcomes. A means of doing this will be through the use of patient-friendly devices (i.e. their smartphone) to gather information and provide real-time feedback. Device familiarity and real-time feedback can create greater patient engagement. "As a result, it is a little easier to educate them about what the clinical research is all about," he states. "Further, they become an active partner, as opposed to a passive participant." He says another opportunity for improvement is the reduction of the number of pages in informed consent documents, which can range from 20 to 50+ pages. The key is to try new approaches and have a willingness to learn from failures as well as successes. positive Phase 3 results for Lilly have led to a record seven regulatory submissions of four molecules in 2013 and the expectation of launching three drugs in 2014 — empagliflozin, which was codeveloped with Boehringer Ingelheim for type 2 diabetes; dulaglutide, a once weekly treatment for type 2 diabetes; and ramucirumab. Just as Lilly continues to learn from its failures, it also does so from its successes. The company designed and conducted an adaptive, dose-finding, seamless Phase 2/3 trial study with dulaglutide. According to Garnett, the design was outstanding, something to be proud of, and probably saved the company about a year on the entire Phase 3 program. "But that savings was lost because we spent a year gaining agreement on the design with the FDA, as well as internally," he laments. Being one of the first companies to do a substantial Phase 2/3 adaptive trial design may have been one of the reasons why it took so long. "We need to take that learning and apply it to the next program. We paid a high price in terms of time because not only did we need to familiarize regulators to the approach, but internally, we needed to develop a level of comfort and confidence with the adaptive design concept," Garnett states. LEARNING FROM FAILURES AS WELL AS SUCCESSES "There were a lot of people within the organization who were "Like every other company, Lilly has had Phase 3 failures, which are nervous about it." The lessons learned from this success include extraordinarily expensive and demoralizing for an organization," gaining alignment on the design internally first, and communicatadmits Garnett. For example, the company announced in December ing your intentions with regulators clearly, frequently, and proacthat edivoxetine did not meet primary end points of Phase 3 clinical tively throughout the process. Garnett feels there is no question studies as add-on therapy for major-depressive disorder. Prior to the dulaglutide adaptive trial design saved the company time. In this, Lilly announced Phase 3 failures of enzastaurin for large B-cell addition, he suspects more companies will begin using adaptive lymphoma, solanezumab for Alzheimer's disease, and ramucirumab trial design because it provides high-quality data, reduces risk, for breast cancer. Despite these and other setbacks, the company and results in a much clearer direction for Phase 3 trials. "This is continues to plow forward, announcing an additional late-stage true as long as you aren't spending too much time on getting folks trial of solanezumab and an FDA priority review of ramucirumab internally aligned on the design," he concedes. Obviously, there is for the treatment of gastric cancer. The lesson to be learned here a fine line to managing the clinical trial paradox when determining isn't to fear failure, but rather to learn from it and overcome — a how much you need to slow down if you want to truly capitalize key longstanding compoon the possibility of being nent of the Lilly culture. able to speed up while For example, in 1999 Lilly improving productivity halted trials of an experiand performance. Having Since completing his medical degree, Lilly's chief medical officer (CMO), Tim Garnett, has mental chemotherapy drug, produced the strongest spent the bulk of his professional career working in the pharmaceutical industry. One of the Alimita, after discovering pipeline in its 137-year hisgreatest challenges he sees physicians face when making the decision to enter the industry is three significant adverse tory, Lilly appears to have adapting to the corporate culture. "Physician training and practice are based on the concept events. Many thought this struck the right balance. At of individual decision making and personal accountability," he attests. "However, pharma might be the end of Alimita. this writing, the company companies are based on collective decision making and joint accountability." This is a conHowever, researchers did had 13 potential medicines cept Garnett thinks many physicians struggle with when joining pharma companies. He says not want to give up on the in Phase 3, the final stage it also can prevent talented medical doctors from realizing their true potential to becoming drug because of the strong of clinical study, or under industry leaders. "I initially struggled with the decision-making processes of the companies evidence it could reverse regulatory review. In addiin which I worked," he admits. "But success in this industry requires an understanding of tumor growth. In this tion, Lilly has 26 more the corporate culture and your role within the company. Once I came to understand this, I case, persistence paid off projects in Phase 2, which became less frustrated with what I saw as slow or illogical decision making, and I was able with the drug gaining FDA is five times more than it to more constructively contribute to the organization's mission." If you want to be a sucapproval in 2004. Today, had a decade ago. For the cessful CMO, Garnett believes you need more than just the technical ability to perform the Alimita has four different time being, slowing down role. "Understand how decisions are made and influenced in an organization so you can best FDA-approved cancer indiand staying the course represent the medical function at the highest level," he advises. cations. More recently, seems a sound strategy. SO YOU WANT TO BE A CHIEF MEDICAL OFFICER? 30 LifeScienceLeader.com February 2014