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Pharmaceutical companies routinely sinkmillions of dollars into common diseases,hoping for a multibillion-dollar payoff from thenext blockbuster drug. But for orphan diseaseswith a small market, there are few takers.

An emerging model for medical research—exemplified by the Cystic Fibrosis (CF)Foundation’s approach to drug discovery—relies on collaborative efforts betweenpharmaceutical companies, academicresearchers, physicians and patients to propeltest tube discoveries to the clinic.

“There is not a lot of incentive forcompanies to invest in orphan diseases likecystic fibrosis,” says Robert Beall, president ofthe CF foundation.“By funding CF drugdiscovery, we ensure that our pipeline ofpotential therapeutics is continuously fed.”

At a conference held in March inWashington, DC, Elias Zerhouni, director ofthe US National Institutes of Health, said thefoundation’s model exemplifies thecollaborative efforts described in his Roadmapfor Medical Research (Nat. Med. 9, 1335;2003). Other organizations, such as theJuvenile Diabetes Research Foundation andthe Institute for the Study of Aging, are

following similar paradigms.Developing a drug from concept to

approval can cost up to a billion dollars. Usingunconventional strategies designed toencourage companies to develop medicines atminimal financial risk, the foundation hopesto lower the cost to about $100 million.

In addition to funds, the foundation givescompanies access to a network of 18 CF carecenters and a patient registry.“The largestproblem in the research of orphan diseases isthe lack of centers with enough patients toenter into a trial,” says Bruce Montgomery,chief executive officer (CEO) of CorusPharma.“The care centers, by standardizingand centralizing care, help solve this problem.”With financial support from the foundation,Corus is conducting a phase 2 clinical trial ofan inhaled antibiotic for treatingpseudomonal infections in CF patients.

The foundation supplies initial funding tocompanies in the form of awards andcontracts and matches companies’ investmentin CF drug research. In return, companiesmust meet certain goals before they receivethe next payment. The foundation typicallyhelps fund phase 1 and phase 2 trials.“Once

they’ve completed those successfully,” Bealladds,“it’s much easier for them to getadditional sources of funding for thedevelopment of a phase 3 drug.”

This integrated model of drug developmentis a “one-stop shop,” says Ed Field, CEO ofInologic, Inc., which is developing acompound to improve the function of CF-struck lung cells. Apart from reducingfinancial risk for companies, Field says, themodel also cuts clinical risk in terms of accessto patients, centralized data management,academic researchers and protocols.“Thefoundation’s integrated network makes it easyfor a company like ours to plug in to,” he says.

Another aspect of the model is findingcompanies with potential CF drugs already intheir pipelines. For example, InspirePharmaceuticals had a drug that wasoriginally targeted for sinusitis. Because someexperts thought the drug might haveapplications in CF, the foundation gave thecompany $1.7 million to develop the drug forCF. The drug did not test well for sinusitis, butInspire recently announced promising phase 2results for its efficacy in CF.

Amy K Erickson, Washington, DC

Collaboration may be the cure for what ails drug development

558 VOLUME 10 | NUMBER 6 | JUNE 2004 NATURE MEDICINE

Columbia University’s medical center is underfire from the People for the Ethical Treatmentof Animals (PETA), which has alleged that theschool’s treatment of research primates violatesNew York state laws.

PETA’s complaints have prompted investiga-tions by the US Department of Agriculture andthe US National Institutes of Health into theuniversity’s potential violations of the federalAnimal Welfare Act. In March, PETA also filed acomplaint against the medical center with theoffice of the Manhattan District Attorney.

PETA began an intense public awarenesscampaign in 2002 after veterinarian CatherineDell’Orto, a former postdoctoral fellow atColumbia, went public with complaints aboutthe treatment of baboons she had observed inseveral Columbia laboratories, particularly inthe stroke therapy research of neurosurgeon E. Sander Connolly.

The study to test potential neuroprotectivedrugs in a baboon model of stroke involvedremoving an eye from each animal to allowtechnicians to clamp an artery and artificiallyinduce a stroke. Dell’Orto reported that anes-thesia was not administered to some baboon

Animal activists take aim at Columbia University’s primate program

subjects, while others were left to die in theircages without being euthanized.

Laboratories are generally exempt from NewYork animal cruelty laws, but scientists may beprosecuted in cases where experiments are“improperly conducted,” says Mary BethSweetland, PETA senior vice president. PETAsays Connolly and his staff failed to observe theresearch protocols and that the experiments“lacked any ‘reasonable scientific justification’.”

Also named in the complaint were membersof the medical center’s Institutional AnimalCare and Use Committee, which evaluates

animal research protocols. Mark Underwood,chairman of the committee, says an internalinvestigation turned up several “deficiencies,”including incomplete documentation andinsufficient post-operative veterinary observa-tion.“Columbia University took the allegationsvery seriously and made immediate and appro-priate corrective action,” says Underwood, whowas not named in the complaint.

Connolly, who did not respond to interviewrequests, has voluntarily suspended the strokeexperiments, Underwood says, adding thatConnolly and others who conduct animalresearch have the university’s full support. “Wefeel that the research is of vital importance tothe mission of saving lives and finding cures,”Underwood says.

PETA and others were buoyed by a recentcritique of animal research, which reported thatmuch of the research is inapplicable to humanmodels and is subject to significantly lowerstandards than clinical trials (BMJ 328,514–517; 2004). The authors concluded that“the contribution of animal studies to clinicalmedicine requires urgent formal investigation.”

Bruce Diamond, New York

Monkey business: Columbia U is under investigationfor potential violation of animal welfare laws.

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