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Rising costs and evolving compound developments underline need for understanding at every step.
Development of a compound in the oncology therapeutic area is constantly evolving, and costs are rising dramatically, making every step count. Three essential assets should be acquired before an oncology trial is launched.
Strong science. A potent compound originates from rigorous pre-clinical models, so these models should take several factors into account, including the selection of the patient populations, the mode of administration of the drug as well as the formulation. The use of pharmacodynamic markers (PD markers), which may lead to the development of a companion diagnostic tool, are also developed during this important first step.
The validation of the appropriate pre-clinical models is the first prerequisite in the development process. Those models will provide some efficacy and safety data and will generate interest in the new compound. This is followed by a series of toxicological studies as defined by ICH guidelines for pre-clinical studies that will define the toxicological profile of the drug to establish the initial dosage in humans. Having a strong model at the beginning of the process will lead to more successful translational studies, meaning more relevant and robust pre-clinical data, which has a direct impact on the potential commercialization of that compound.
Academic/biotech researchers are creative minds that must fit within stringent regulatory and commercial boundaries. This can sometimes be a challenge when faced with the competitive realities of compound development, where profit potential and opportunities for licensing deals may trump scientific interest. For small drug companies especially, the early stages of development are the most challenging from a financial standpoint as well as in terms of innovation. To avoid costly missteps along the way, it can be prudent to rely on the guidance of those who have been through the process before.
Visionary drug development plan. A robust scientific model alone will not guarantee success. The science behind the product must show more than a strong hypothesis in addition to reliable results. It also needs to be innovative and, more importantly, resistant over time.
Developers will see a much greater return if they invest time and money in adapting their technology to fit a long-term development plan. Scientists must see beyond the limits of good fundamental science and open themselves up to the clinical necessities and daily realities of both medical oncologists and their patients for a longterm,visionary drug development plan.
In the short run, a development plan should include the feasibility throughout all phases of clinicaltrials (from Phase I through III). Long-term development plans present the biggest challenge for developersbecause they not only need to define the product placementin today’s market but for as long as 10 years down the road.
This involves not just the product, but also the standard ofcare and comparator compounds to be used throughout theclinical development process to accurately assess the drug’sefficacy. Developers are increasingly likely to invest in comparativestudies to ensure they are launching accurate, state-of-the-art products. This will require help from marketing toforesee what the comparator drugs are likely to be over thenext 5-to-10 years. This long-term projection is also applicableto patent life, which also presents competition from genericequivalents that are impossible to avoid.
The National Cancer Institute is currently conducting multicenter trials to test a new method of monitoring patient adverse events through the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Event (PRO-CTCAE). The PRO-CTCAE provides a web-based platform to collect patient reports of symptoms they are experiencing while undergoingtreatment, for the purpose of enhancing adverse event reporting.1
PRO-CTCAE is based on findings that suggest the reporting of adverse events directly from the patients is significantly correlated with measures of functional performance and health status, as opposed to adverse events reported by clinical staff.2 This secure, web-based platform for patients, investigators, and clinicians is also thought to be more accurate and reliable than patient self-report questionnaires and allows adverse events to be directly reported by cancer patients taking part in clinical trials, instead of having them interpreted and modified by clinical staff to fit the CTCAE.
A visionary development plan that is open to more sophisticated patient-tailored tools and that shares long-term clinical goals with every stakeholder touched by the disease, i.e. developers, investors, medical and para-medical teams, patients and their relatives, will contribute greatly to the optimization of treatments against cancer.
Strategic advisors & strong leadership. Bringing together a strong leadership team that can pull in complementary experts and strategic partners to help get it all done on time and within budget is recommended.
These partnerships will bring different expertise to the multifaceted challenges faced during the drug development process. These can include, among other things: refining the technology; overseeing the regulatory requirements and ensuring quality assurance; managing pharmacovigilance; facilitating operations during clinical trials and accelerating the overall trial process; developing or advising on software; elaborating and launching the business and commercialization process; developing patents and providing legal advice; and promoting collaboration with Key Opinion Leaders in the industry.
The medical oncology community is key to helping drug developers uncover real-world needs of patients and are, therefore, essential throughout the drug development process. But, strong and trustworthy alliances with medical oncologists is not always a given for biotechnology companies. However, a CRO that specializes in oncology may deliver an added advantage as it already maintains strong relationships with oncologists, which will facilitate the collaboration between sponsors and potential investigators or other clinical oncology experts. CROs may also offer specific services in various activities from early to late stage product development. The expertise of both the medical oncologist and the CRO will combine to help transpose preclinical models into the reality of the clinical world and in doing so will optimize translational studies.
A CRO may also work closely with the developer’s scientific team in early stage phases to reevaluate the objectives of the trial and the protocol design according to the industry’s requirement, and taking into account trials that are currently active. They will also help select the most qualified research team to facilitate patient enrollment and improve the quality and integrity of the data.
Beyond the scope of clinical trials, there are a variety of other qualified experts that can help create strategic alliances with larger groups or pharmaceutical companies. It is important to note that the choice of the right partner, no matter what stage of drug development, can limit risk and improve the chances of compound success. With the right team and partners in place, early termination of a trial for reasons other than patient safety does not necessarily imply the end of the product. Strategic partnerships and strong leadership can often turn around a situation that was once considered a failure.
There is no silver bullet to curing cancer, just as there is no magic recipe for the success of a clinical trial. Every step along the drug development journey brings specific results that will contribute to the big picture and add to the advancement of clinical research. Knowledge, rigor, leadership, good judgment, open-mindedness, patient-centricity, and of course strategic alliances are all critical components in achievingsmall victories towards enhancing patient outcomes.
Catherine Ménard is a Lead Clinical Research Associate at Scimega Research Inc. She can be reached by e-mail at [email protected].
Roberto Lara* is Director of Business Development at Scimega Research Inc. He can be reached by e-mail at [email protected].
*To whom all correspondence should be addressed.
2. Basch et al. Electronic toxicity monitoring and patient-reported
outcomes. Cancer J. 2011; 17(4).