By Cindy Dubin
The success of companies that rely on outsourcing for the development of new pharma products can be intrinsically linked to the partnership with the CRO. Savvy life science leaders recognize this and, thus, revenue for U.S. CROs is set to soar from a total of $11.43B last year to $20.09B in 2017, forecasts a new report from Frost & Sullivan. While the economic downturn did take a toll on most markets in 2009, the CRO sector managed to buck the trend, growing 8.5%, says the study.
While the slowdown in funding for early-stage projects has dampened the CRO market’s prospects for the next three to four years, this lack of funding also has restricted companies from investing in in-house clinical trials, creating opportunities for CROs. Analysts are optimistic about continued growth due to interest shown by new sponsors, especially biotechnology and specialty pharmaceutical companies that are demanding full services from their CROs, from the preclinical to postcommercialization stages.
Getting The Right Fit
Selecting a CRO is not a one-size-fits-all proposition. The CRO should be specific to the project, have access to the correct patient demographic, be knowledgeable about the therapeutic area, and exhibit a level of expertise in project management.
These were the qualities that Galena Biopharma, Inc. (formerly RXi), a Portland, OR-based biopharmaceutical company, sought as it set out to begin a Phase 3 clinical trial. Galena develops targeted oncology treatments that address major unmet medical needs to advance cancer care. The company is developing NeuVax, an off-the-shelf peptide vaccine based on the concept of active immunotherapy. NeuVax targets patients who achieve a remission with current standards of care, but have no available adjuvant treatment for maintaining their disease-free status. The intradermal injection is given once a month for six months, followed by a booster injection once every six months. Based on a successful Phase 2 trial, which achieved its primary endpoint of disease-free survival, the FDA granted NeuVax a special protocol assessment (SPA) for a Phase 3 clinical trial in adjuvant therapy of women with low-to-intermediate HER2+ status. An SPA is a declaration from the FDA that a prospective Phase 3 trial’s design, clinical endpoints, and statistical analyses are acceptable for FDA approval.
According to the National Cancer Institute, more than 230,000 women in the United States are diagnosed with breast cancer annually. The currently approved Herceptin (trastuzumab by Roche-Genentech) monoclonal antibody treatment is indicated in women with tumors that over-expressed (3+) HER2, which represent 25% of patients, while NeuVax targets the remaining patients with low-to-intermediate over-expressing (1+/2+) HER2 tumors — representing a targeted personalized therapy for about 40,000 to 50,000 patients annually. NeuVax attempts to harness and boost the body’s immune system to seek out and fight off cancerous cells. Herceptin had revenue of more than $5 billion in 2010, approximately half of which was in the adjuvant setting. Mark Ahn, Ph.D., president and CEO of Galena Biopharma, expects NeuVax to satisfy an unmet medical need and that the drug has blockbuster opportunity.
The Nuances Of An SPA
Ahn admits Galena needs a little help achieving the goal of becoming a blockbuster. So while Phase 1 and 2 clinical trials of NeuVax were performed in-house, the management team at Galena decided that outsourcing the Phase 3 trial, expected to commence in the first half of 2012, was necessary. Much of this decision was based on the multinational nature of the study. One hundred sites will participate in the United States, Canada, and Europe.
As clinical trials become ever-increasingly complex and global, the competition for access to patients, new investigators, and fresh studies is heating up. The gap between patient access and trials has been rising consistently over the past decade and could affect future projects, states the Frost & Sullivan report. CROs enable access to an extensive patient pool.
Galena needed a CRO partner with global reach and locations in sites with the standards of care that would adhere to the protocol. “The results from each site have to be comparable, and the way to ensure that is to be certain the standards of care at all locations are similar,” says Ahn.
In addition, all of the 700 patients who will participate in the 36-month study must be appropriately screened, and their data must be easy to electronically access on a timely basis.
The selection process took about six months and included screening about 12 candidates, then whittling the list down to 4 who were sent detailed requests for proposal. “Galena conducted a very professional, rigorous, and thorough evaluation of clinical research service providers to conduct its trial,” says Gene Resnick, M.D., chief medical officer of Aptiv Solutions, a CRO headquartered in Reston, VA.
Galena provided a framework of specifications and requests in the RFP. In addition to providing the standard information regarding therapy area expertise, relevant study experience, global footprint, and staffing/resources, Aptiv Solutions provided information specifically focused on the Galena study. For example, the CRO provided detailed analysis of site distribution and enrollment projections, feasibility assessment for the trial, statistical modeling for adaptive design features, and regulatory timelines. These items proved valuable to Galena in study planning and provided a basis for discussions and study implementation.
During the assessment process, Galena also asked questions such as:
Does the CRO have experience in the same disease indication?
Is there a proven network of clinical sites?
Does its project management have a proven track record of handling a similar level of complexity in drug product?
Can it perform careful patient screening?
Will it perform CRA follow up?
Is there a database lock and data safety monitoring board?
Ahn says, “After a careful review of these details and an intensive in-person meeting, we felt Aptiv Solution’s knowledge in oncology and its international presence in more than 20 countries participating in the study made it a logical choice for handling the Phase 3 trial called PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment).”
Aptiv Solution’s clinical trial team will manage the PRESENT trial start-up and all related clinical trial activities for global implementation, including consideration of adaptive trial design strategies. This includes project management services, data management collection, statistical analysis and reporting, pharmacovigilance, and regulatory filing.
One of the biggest challenges the CRO will face in performing the Galena clinical trial is adhering to the established 36-month deadline of enrolling the right patients. “While breast cancer is unfortunately a common disease, only certain subsets are eligible for this study,” says Resnick. For instance, the patients cannot be eligible for treatment with Herceptin, and they also have to exhibit certain markers of potential immune responsiveness.
Galena also needs Aptiv Solutions to handle the study’s design nuances as they relate to the SPA. An SPA provides a significant advantage for companies because the rules of assessing safety and efficacy are prespecified, explains Ahn. “It is incumbent on the sponsor and the CRO to carefully adhere to the protocol to maintain the viability of this regulatory pathway,” he says.
Adherence to the agreed protocol specifications and processes will be essential. “The protocol is established and set, and no changes can be made during the course of the study,” reiterates Resnick. “Galena had to be sure that whatever CRO it chose could understand how to analyze the data of such a study and represent the findings to the FDA in a way that satisfied the protocol.”
Relinquishing Control ... Somewhat
Because NeuVax was developed at the University of Texas MD Anderson Cancer Center and the Brooke Army Medical Center in San Antonio, these facilities will comprise 2 of the 30+ U.S.-based sites for the PRESENT trial, making them important partners in this project.
Just as important is establishing a collaborative partnership with the CRO, agree Ahn and Resnick. The two groups will meet weekly throughout the study, and while Galena plans to actively manage the study, Aptiv Solutions will take ownership of the project. “Having this collegial partnership relieves the tension and helps work through the bumps that are sure to come down the road,” says Resnick. “If we work as a team with the same goal in mind, the relationship will work.”
“Hiring a CRO is not abdication, but a partnership, born of an assessment that using their operational infrastructure and experience is more efficient and less risky than creating a new multinational team,” says Ahn. “The collaboration of a biopharmaceutical and a CRO shows the best that this industry has to offer.”