17 March 2011. At the last of a series of preparatory meetings by the Alzheimer’s Prevention Initiative, held on 7 January 2011 in Washington, D.C., API scientists impressed the audience with the work the team had done over the past year. They have the patients; they are gathering the biomarker data; they are finding suitable cognitive tests. The regulators expressed interest in the proposed trials. Adaptive designs were discussed. Beyond that, however, the scientists will come to a standstill without knowing which therapies the biopharma industry will lay on the table for these trials. “We are in striking distance of concrete designs. It hinges on specific therapies,” said Pierre Tariot of the API. “Now the field is stuck at the drug choice question,” agreed Michael Grundman of Global R&D Partners.

So, what about it? As at the previous API meeting held in Phoenix in 2010, industry scientists were coy about the topic, and no drug name came up the entire day. Differently from that meeting, though, the biopharma contingent took some flak for that stance. In particular, William Potter, formerly of Merck but now a consultant for the Foundation of the National Institutes of Health (FNIH) and other groups, pressed his colleagues. “Let us be more transparent. I am surprised that companies are not sharing more here. We can at least discuss criteria for testing and choosing drugs for these trials openly.” Other industry scientists agreed that ways of assessing and presenting data could be defined pre-competitively without one company seeing another’s raw data.

When biopharma scientists cited resistance among their senior management to sharing data and advancing candidate drugs for preclinical populations, they were asked to stop hiding behind senior management. “I do not understand our throwing up that our immutable senior management is to blame. It is not true. If we believe sharing and collaboration is important, then we have to take up this fight internally,” said Potter. And this from Maria Carrillo of the Alzheimer’s Association, “We need to stop talking about what can’t be done and to start talking about what can be done. Be as open as you can and bring senior management to these discussions.” Collectively, the group knows sharing initiatives are possible. For example, the C-Path Institute’s Coalition Against Major Diseases has developed a shared trials database, and a similar ADCS/FNIH/Alzheimer’s Association project exists as well.

Some progress has been made. Since its own regulatory meeting in London last October (see ARF related news story), Dominantly Inherited Alzheimer Network (DIAN), whose own enrollment stands at about 150, has received 10 non-binding therapy nomination packages from pharma companies. In Washington, D.C., Randy Bateman of Washington University, St. Louis, told the audience that those 10 compounds are not discontinued has-beens, as some skeptics had predicted early on. On the contrary, Bateman, said, they are the lead therapeutic candidates in the field. “That there is this amount of support from the companies to offer up their best compounds for these treatment trials is very hopeful for DIAN, for the Alzheimer’s Prevention Initiative (API), and for the Alzheimer's Disease Cooperative Study (ADCS),” Bateman said. For its part, the API is talking individually with drug companies.

In the process, though, both API and DIAN—small operations run by teams of academic scientists and their administrative staff—have been burdened by having to execute dozens of confidentiality agreements. These tie up resources these groups want to put to better use. In discussion, suggestions came up for an independent group, such as CAMD or FNIH, to lend resources and expertise. CAMD has a track record in getting companies to share trial data and to adhere to, or even convert to, a shared data standard; FNIH’s Biomarker Consortium manages the I-SPY 2 trial that could serve as a model. The idea of data-sharing generated a buzz among researchers who noted that small populations such as the one in DIAN afford few opportunities to repeat tests, as well as others who want to move the preclinical trials project toward the I-SPY model.

“I-SPY is very exciting to me. Having several treatments in parallel is fascinating. The issue for us now is that 10 companies have submitted packages to DIAN, and companies are talking with API. Unless we know who they are, how are we going to move toward I-SPY? Let’s do this offline. Guys, you know my e-mail address,” said one senior pharmaceutical company scientist (name withheld).

Concluding the meeting, Eric Reiman of the Banner Alzheimer’s Center in Phoenix, Arizona, said, “Imagine one of you in this room had a drug to stop the development of a fatal disease and we did not know it. Now is the time when we have a unique opportunity to advance the evaluation of a range of pre-symptomatic compounds in the most rigorous and efficacious way. We are determined to move forward. We are heartened by the regulatory feedback. Now we look forward to engaging you.”—Gabrielle Strobel.

This concludes a six-part series. See also Part 1, Part 2, Part 3, Part 4, Part 5. View a PDF of the entire series.