The early bird may get the worm, but it has little chance of competing in the technologically explosive world of neurological biologics. The bird hatched from its shell with the worm gripped firmly in its beak is the one that will survive and be successful. With some of world's most desperate patients looking to the industry to cure a host of devastating conditions, effective marketing strategies and communications plans must be hatched during research.

The experts agree that the super-customized treatments of the future will make blockbusters a thing of the past. All in all, the top ten marketing challenges facing any company planning to license, manufacture, or distribute any of the most exciting therapies in neurology cannot be ignored. They're on their way-ready or not.

Targeting Multiple Stakeholders

The key to building a solid foundation for marketing in the Bio Age is balancing the urge to excite newly redefined audiences with the caution needed to avoid overselling the potential of new research and treatments. "Professionals" might be key investigators who need special attention up front just to be persuaded to recruit clinical trial patients, according to Anne Devereux, president and COO of Merkley Newman Harty Healthworks. She says the role of "patient" will often be played by family caregivers when patients themselves are unable to make their own medical decisions. So, although that group is traditionally a focus of early marketing plans, it is unusually well informed and may not need as much promotional contact as other therapeutic areas. Patients and their caregivers are likely to influence others in the hierarchy, every step of the way.

"The biggest challenge for marketers in this field will be to design meaningful clinical endpoints to accomplish multiple tasks for multiple audiences," says Larry Star, chairman and CEO of the Harrison and Star Business Group. "Until now, endpoints for new treatments for ALS, for example, were death and time to intubation. Those were acceptable for FDA, but what does that say to patients? What about quality of life and other measures that are clinically relevant to patients and their doctors?"

Massive education efforts must accompany the continuous monitoring and refining of messages that will be simultaneously delivered to those audiences to ensure the messages are received by informed ears, especially within the investment community. As sophisticated as analysts may be, many still fail to grasp the complex fundamentals of biological research, such as vector selection, immunologic side effects, and risk management.

"I liked the idea behind Maxim's drug Maxamine," wrote Lissa Morgenthaler, who runs the Monterey Murphy New World Biotechnology Fund, in a December column for RealMoney.com. "But I couldn't wrap my brain around 'subcutaneous administration of histamine,' so we never recommended the stock in our newsletters and didn't own any this week."

The challenge is to gently demystify the mechanics of biologics for a varied and fragmented audience that might not rapidly embrace the technology otherwise. But the messages must be clear and consistent.

Star recommends that companies "take a long, hard look at what they're telling everyone and paint a realistic picture of what they'll be able to deliver. Otherwise, the drug will be deemed a failure, no matter what happens in the future."

Navigating FDA

Demonstrating medical necessity will not be a problem in the areas of degenerative brain disease, spinal cord injury, demyelinating diseases, or other severe neurological conditions. The safety of any potential breakthrough is paramount at this early stage of the game, and that's what researchers are working to demonstrate before they prepare regulatory submissions or even consider human trials. Other concerns are speculative, according to Jeffrey H. Kordower, PhD, professor of neurological scien-ces and director of the Center for Brain Repair at Rush-Presbyterian-St. Luke's Medical Center in Chicago.

Although he has yet to submit an application to FDA, Kordower anticipates that the first hurdle will be showing the agency that his gene therapy for Parkinson's disease has an established regulatable promoter-that it's possible to turn off the gene that is turned on during treatment if something goes wrong. He's also concerned that FDA will support therapies for advanced- or end-stage disease, whereas his research focuses on early-stage patients, for whom the clinical implications could mean neuroprotection and, possibly, regeneration. But the promise of early intervention is diluted by the risk of toxicity to patients who are not yet disabled by the disease and who still have some palliative options with currently marketed medications.

"Essentially, what we're talking about is asking FDA to let us operate on not-too-sick patients and inject them with inactivated AIDS virus," says Clif Hotvedt, vice-president of medical and scientific affairs at Ketchum Public Relations.

That characterization is an oversimplification, and it's unlikely that patients themselves will be reluctant to enroll in trials if their prognoses are bleak. Kordower generally doesn't worry about public concern for the perceived risks of administration vectors such as viruses, which are molecularly restructured to be safe.

"As long as FDA allows us to do it, patients' physicians can explain how it works, and that it's safe," he says. "They can explain that the potential risks are small and that the potential benefits are great, and if that's accurate at the time that we're in trials, I don't think it will be a problem."

Managing Expectations

Assuming that regulatory hurdles are jumped and clinical trials begin, the industry must prepare for an overwhelming flood of volunteers virtually begging to enroll-not to mention their emotionally driven caregivers whose expectations might exceed even those of their loved ones.

"Of course patients and families are going to be driven to enter these trials," says Denise Bottiglieri, PhD, chief operating officer for Health Science Communications-CME. "The challenge is to manage excitement levels and set up realistic expectations for them, so that the company doesn't have a public relations nightmare from the start."

Overselling any technology or its promise can backfire with physicians, resulting in a serious consequence-their abandonment of patient recruitment for the trials. Again, thorough education concerning mechanism of action, study design and methods, and realistic outcomes are key to filling study rolls and maintaining solid relationships with the customer-to-be, the referring physician.

Minimizing the Impact of Public Rhetoric

Never was the double-edged sword as sharp as it is now, with the advent of the Bush Administration. On one hand, it promises to make the political climate veritably balmy for the industry, according to pharmaceutical and biotech analysts at Merrill Lynch. They predict significant revenue and earnings growth, and most important, the relegation of price controls to the back burner of national debate. On the other hand, biological research is faced with the devastating threats of restrictions on federal funding for stem cell research.

In the face of those threats, researchers will have to simultaneously educate and lobby confused legislators to maintain their vital sources of human biological materials. According to an essay posted at BrainTalk.org by Parkinson's disease patient and advocate Michael J. Fox, the opposition's support for a ban is based on the inaccurate entanglement of stem cell research with the abortion issue:

"Mr. Bush favors a ban on stem-cell research, one aide said, ?because of his pro-life views.' Yet stem cell research has nothing to do with abortion. It is not the same as fetal tissue research. Currently more than 100,000 embryos are frozen in storage-most of them are microscopic clumps of cells destined to be destroyed, ending any potential for life."

Thus, researchers will have an uphill battle to teach misinformed decision makers about the realities of their research methods, to protect their current sources of material and lobby for funds for the discovery of alternative sources of stem cells from adults.

A similar but more comprehensive public relations effort is necessary for those involved in genomics, where the public's fear of the industry "playing God" poses a legitimate threat to research-if those voices are heard loudly enough on Capitol Hill.

Educating Customers-to-Be

Most office-based neurologists have some grasp of the science behind breakthroughs in genomics and biologics, but not nearly enough to enable them to identify or refer patients with confidence. The industry will have to take responsibility for providing them with the fundamentals they need to appropriately dispense advice and explain complicated concepts to intimidated patients.

"Right now, the level of understanding about genetics on the primary and specialty care level is on par with nutrition," says Charles Marshall, one of a group of geneticists who launched GeneSage. "Those are two areas in which they refer patients out, but the problem is that questions are coming up so rapidly that there just aren't enough geneticists out there to handle the demand."

GeneSage's online programs aim to translate the complex language of genetics for primary care physicians so they can understand the underpinnings of diseases and their gene-therapy treatments and pass the information on to their patients. Pharma companies can sponsor CME programs that give doctors a basic genomic education, databases of clinical trials, patient education materials, and content demonstrating how applicable a company's therapy is to the treatment of their patients' conditions.

"Specialists and even primary care physicians and general practitioners will have to learn about genomics and the other new technologies that will revolutionize the practice of medicine," says HSC-CME's Bottiglieri. "They'll be working in an entirely different environment in which genetics counselors play much larger roles, and patients have much greater financial responsibility for their own care."

Influencing Reimbursement Policy

Actuaries may already be calculating the tremendous costs associated with the sophisticated surgical procedures necessary to deliver some of the gene therapy, stem cell, and growth factor treatments. Their conclusions may already mean trouble for patients and their families, who will inevitably bear most of the cost burden for their care.

NeuroInvestment editor and publisher Harry M. Tracy, PhD, predicts that companies won't bother to tackle the issue until they absolutely have to. "They have years to conquer so many other battles before this one comes up," he says. "But they might have to come up with a strategy to convince the powers that be to look more at the long-term savings that offset the front-end costs."

Although the Bush Administration's urgency to address the Medicare prescription drug benefit issue is unlikely to impact neurology therapeutic areas, in which so many patients are elderly, Tracy foresees the involvement of government subsidies in both the self-pay and managed-care markets.

Reaching Out to Patients

Given the activist nature of the patient/caregiver group in the neurological area, they're unlikely to be the focus of mass promotional activity, as is the case with DTC plans for traditional pharmacologic treatments. They are generally well-educated, well-informed, and well-connected, getting their information from support networks, scientific journals, and their many sophisticated online exchanges with the research community.

The big question is: Will it be possible to craft custom-made messages for the masses? The beauty of many of the treatments coming out of Bio Age research is their ability to target the needs of individuals, according to their condition, needs that are perhaps unlike any other patient's. Experts will be crucial in advising their pharma clients how to target individuals with messages designed specifically for them.

According to Devereux, the first step is identifying the best communications vehicle to bridge the gap between the physical and emotional impacts of breakthroughs. "For example, a nurse in the doctor's office or the hospital may be the best marketer," she suggests. "We've seen this in oncology as well as in multiple sclerosis, where the nurse is the manager of the patient's care and is often the most reasonable person to educate patients, make sure they understand the treatment, and tell them what to expect."

"The ideal continuum of care would include communications as part of the therapy," says Andrew Schirmer, executive vice-president and creative partner at Merkley Newman Harty Healthworks.

Choosing Partners

The financial news is full of stories about tiny preclinical labs announcing licensing deals with small and midsized biotech companies that invested in their research to bring promising compounds to clinical trials. So far, Big Pharma has been reluctant to make what they consider risky entrepreneurial arrangements, according to NeuroInvestment's Tracy. He says that small researchers will continue to ally themselves with small pharma and biotech companies and might need to partner with the big boys only when they're ready to sell products.

In the meantime, resourceful scientists like Rush-Presbyterian's Kordower are well on the way to ensuring their legacies by identifying opportunities that help pay the bills and pave the road to human trials. Simultaneously, smart companies are on the lookout for opportunities to be active partners in the breakthrough business. Their challenge is to find the right researchers who need what they have-or want-to offer, such as materials, facilities, or manufacturing support.

Kordower is a founding scientist of a newly formed company called Ceregene, which recently became a subsidiary of Cell Genesys, a cancer vaccine and gene therapy developer that also acquired the biotech company Chiron. That multifaceted partnership offers Cell Genesys more depth in gene therapy without diluting its core focus. It offers Kordower and his team access to Cell Genesys' patented gene delivery systems and resources, which he needs to move his research forward.

"The main reason we got into this is that we couldn't bring gene therapy into the clinic in the way that we'd want to or with the speed that we'd want to by ourselves," Kordower explains. "Almost anyone who has technology that puts them in a leadership position and is really looking toward clinical trials has already allied themselves with a company or has started their own company."

Managing the Message

Everyone in the organization must speak the same language. In other words, the message should be the same no matter who's delivering it or receiving it. "The same words being spoken by the president of the company to an investor should be spoken by the public relations people talking to reporters," says Star. That is much easier said than done, however, because audiences vary in their levels of understanding, their emotional and/or financial investments, and their dispositions toward the subject.

Preparing for Litigation

The phrase "informed consent" may well be the industry's best friend when it comes to preventing the inevitable costs of personal injury claims and other litigation. Michael Welner, MD, a forensic psychiatrist and chairman of the New York City based Forensic Panel, believes that patients are best recruited for clinical trials through doctors' offices rather than through public information or general solicitation.

"For doctors treating a certain patient population that may be right for these trials," he says, "it's important that they introduce the potential for the technology and the experimental protocol availability to the patients and make appropriate referrals rather than solicit referrals from the community."

Welner suggests that pharmaceutical companies may not only be responsible for the quality of their treatments, they'll have to meticulously train doctors to use appropriate language when recruiting trial subjects to avoid paying for the mistakes of their investigators, who might oversell results to potential study recruits.

"You can't get around the information that's out there, so companies will have to know that if someone comes through a broader net, they'll need to be handled more carefully," Welner says. "A finer net makes sure that the subjects attracted to the study are prepared to engage and to deal with all of the potential outcomes."