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Michael Russo is a partner at the Bruckner Group, (www.brucknergroup.com) a consulting firm assisting pharma and biotech companies with strategic, marketing, and development issues.
The historic divide between academic research and the pharmaceutical industry is disappearing as new research collaborations, drug discovery programs, partnerships, and an evolution in attitudes erases the distinctions that have kept the two at arm's length.
The historic divide between academic research and the pharmaceutical industry is disappearing as new research collaborations, drug discovery programs, partnerships, and an evolution in attitudes erases the distinctions that have kept the two at arm's length. Partners HealthCare Systems (PHS), a non-profit healthcare provider in Boston that integrates primary and specialty care, community hospitals, and academic medical centers affiliated with Harvard University, is helping to lead that revolution with programs that are breaking new ground in the arena of academic–industry partnerships. (See "Academic Alliances," PE's Priming the Pipeline supplement, November 2002.)
Far-reaching changes in academia/industry interactions are underway, and the PHS model coupled with the peculiar problems of treating neurodegenerative diseases illustrates how those changes stand to benefit pharma and biotech companies. John Montana, business development manager at Partners' Research & Ventures group, fills in the details about the prototype initiatives and discusses the state of neurodegenerative disease treatment development.
Historically, academic research related to medicine focused on basic science, generally avoiding marketing decisions. Industry, on the other hand, has focused on drug discovery and product development. PHS is bridging the gap between those disparate roles, using its Program in Neurodegenerative diseases (PND) as a test model for promoting applied science and industry partnerships. (See "Discovery: Neurology," PE, February 2001.)
Representing more than 100 neuroscientists and clinicians, the program focuses on building industry relationships in four major disease areas: Alzheimer's, Parkinson's, ALS (Lou Gehrig's disease), and Huntington's disease. At the PHS hospitals, which include the Harvard-affiliated Brigham and Women's and Massachusetts General hospitals, investigators are doing cutting- edge research in basic neurology, neurodegeneration, neuroregeneration, and therapy development. "All of which," Montana maintains, "show promising results and the likelihood of making a quick jump to a drug discovery program." The best example of that translational style of academic research exists at the Laboratory for Drug Discovery in Neurodegeneration (LDDN), a unique academic neuroscientific drug discovery facility founded in 2001 by the PND and now operating within the newly established Harvard Center for Neurodegeneration and Repair.
Montana explains, "Until recently, assay miniaturization, high-throughput screening, medicinal chemistry, and lead compound optimization have been the exclusive province of biopharmaceutical companies. LDDN is one of the earliest-if not the first-academic drug development programs to encompass all of those components and to seek viable lead compounds for eventual clinical testing. We aren't just looking for interesting science; we are developing novel therapeutic agents for currently untreatable diseases."
In contrast to industry drug-screening programs, which address conservative targets that have been rigorously investigated, LDDN focuses on alternative approaches and targets that, though high-risk, offer high rewards in potential breakthrough discoveries. Although the approach, from a market perspective, is too perilous for the pharmaceutical industry, Montana and the LDDN leadership believe that its intellectual merit, benefit to society, and potential fiscal rewards are great enough for an academic center to justify its use. (See "Spreading the Risk," page 72.)
With LDDN, PHS and its affiliated institutions have almost all of the components in place to bring a medication to market, excluding manufacturing, which could be subcontracted. "Although it is the dream of many at PHS to bring a drug to market by ourselves," says Montana, "the most important thing for LDDN is the quick transition of our discoveries into marketed treatments for disease."
To that end, the Research and Ventures group is developing a variety of commercialization models, including the traditional industry partnership. Montana has begun discussions with several pharma companies about a variety of options and is emboldened by their responses: "We're exploring a range of forms for these partnerships to take," he says. One approach is to develop a strategic alliance with a single company, providing it with an exclusive "first look" at LDDN's pre-publication data, while PHS retains the intellectual property rights, publishing rights, and the ability to build its drug library.
Another paradigm has LDDN identify and approach companies on the more typical case-by-case basis, depending on the disease state and lead compound involved. In that model, the collaboration would reflect the development state of a specific project. A late-stage lead compound could be out-licensed directly, while a promising early- stage compound could be jointly developed through an industry-like partnership between the company and LDDN. Companies are eager to buy validated leads that can fit directly into their pipeline, but they appreciate the decreased costs of collaborating on early-stage projects. Montana says there is room for both at LDDN.
Montana is excited by the recent high-profile developments taking place in the field of neurodegenerative diseases. "The first wave of testable neuroprotective agents for Alzheimer's and Parkinsons's are in the clinic." That is relevant because, until now, the treatments available for those diseases have been palliative in nature, not curative. Many clinicians argue that existing treatments do nothing to stall the diseases' progress. And eventually, when much of the brain has been destroyed, symptomatic treatments simply stop working.
"Neuroprotection is the big thing in neurodegenerative disease research at the moment," Montana says. What is extremely interesting to scientists at PHS are the incredible similarities in the pathogenesis of all the neurodegenerative diseases. Although completely different in genetic pathway and clinical manifestation, each disorder appears to involve an abnormal protein aggregation in the brain. The proteins are different in each case, but the chemistry is similar. One theory is that a therapeutic strategy that is effective in one disorder may prove effective in the others.
"We're all holding our breath for the release of the first product with an indication for neuroprotection," Montana states. "How that medication is received by patients, payers, and the public, and how doctors use it, will set the stage for all those next-generation treatments that follow and will tell us if these neuroprotective strategies will be effective."
He is concerned about more than just the efficacy of this first generation of drugs. He points out a major barrier to commercial success beyond "simply" bringing new therapies for the disorders to market: "Neurologists believe strongly that the efficacy of treatment for neurodegenerative diseases will be proportional to how early the disease is diagnosed, and diagnosis in this field is a major problem."
Currently, by the time Alzheimer's is diagnosed, patients have already lost a formidable portion of their brains' critical neurons. For newly diagnosed Parkinson's patients, the loss of dopaminergic neurons is more than 50 percent. Although neuroprotective therapies prevent further neuronal loss, they cannot regenerate the neurons that are already dead. So treating patients when the disease manifests itself is generally too late for maximum effectiveness. Therefore, early diagnosis is critical to the therapeutic process-and to the financial success of the therapies.
Having neuroprotective drugs available will ultimately change how doctors diagnose and treat the diseases. And, given that symptomatic treatments already sell well, Montana believes, "neuroprotective treatments that really work will sell through the roof." It is only a matter of time before they are available. (See "Disturbing Growth Predicted.")
Despite solving significant medical problems, such treatments are likely to cause a slew of payer issues. The diagnostic tests for Alzheimer's, Montana notes, are extremely expensive and relatively unvalidated. Once early-intervention neuroprotective agents become available, developing and making validated diagnostic tools are unlikely to be inexpensive. Given that the Alzheimer's patient population is elderly and, therefore, largely covered by Medicare and Medicaid, some difficult funding issues will have to be resolved.
Although some people view dealing with a funding problem as the main barrier to treatment as a luxury rather than dealing with a lack of treatment options, what remains is that the pathway to treatment availability is changing as a result of new approaches such as PHS'. "The formerly hostile division between industry and academia is quickly and quietly disappearing," Montana says, "and these developments are being well received in both industry and academia."
Montana observes that attitudes have definitely changed, as "academics no longer see having industry ties as 'selling out.'" He indicates that a large number of academic scientists sit on the advisory boards of companies and participate in both worlds. "Doing a post-doc fellowship in industry is no longer seen as career suicide," he says. "It used to be that once an academician went into industry, he or she never returned to academia, and that's not necessarily the case now. Academia is beginning to see industry more on a peer level, and I think you'll continue to see a blurring of the divide between the two as we move forward."
What is being lost as those two worlds increasingly overlap? Montana says it is clear that academic research is becoming more market-driven, and, as industry becomes a more significant funder of academic research, the for-profit sector's influence on what gets studied will grow correspondingly. What is needed, he suggests, is stepped up funding from the National Institutes of Health and private foundations to support basic scientific research, especially in diseases with low market potential, to prevent market forces from redirecting critical and limited academic resources elsewhere.
"I believe that academia will always remain a safe haven for risk-taking and alternative approaches to scientific problems, and that industry recognizes the innate value in preserving that role for academia," Montana says. He adds that there is real value, from an industry perspective, in letting academia absorb the risks and costs of critical upfront work and stepping in at a later stage to in-license or partner on significant developments.
Yet, Montana believes that the trend is clearly for greater collaboration between academic and industry researchers and that the opportunities for significant disease breakthroughs are much greater as a result.