[It is interesting to see PBS & NPR cited as the business model for a pharmaceutical company.]
July 31, 2006 A Small Charity Takes the Reins in Fighting a Neglected Disease By STEPHANIE STROM NY Times http://www.nytimes.com/2006/07/31/health/31charity.html?ei=5094&en=ab1f6edfebb0ef03&hp=&ex=1154404800&partner=homepage&pagewanted=print PATNA, India The drug that could have cured Munia Devi through a series of cheap injections was identified decades ago but then died in the research pipeline because there was no profit in it. So Mrs. Devi lay limp in a hospital bed here recently, her spleen and liver bulging from under her rib cage as a bilious yellow liquid dripped into her thin arm. The treatment she was receiving can be toxic, and it costs $500. But it was her best hope to cure black fever, a disease known locally as kala azar, which kills an estimated half-million people worldwide each year, almost all of them poor like Mrs. Devi. Soon, however, all that may change. A small charity based in San Francisco has conducted the medical trials needed to prove that the drug is safe and effective. Now it is on the verge of getting final approval from the Indian government. A course of treatment with the drug is expected to cost just $10, and experts say it could virtually eliminate the disease. If approval is granted as expected this fall, it will be the first time a charity has succeeded in ushering a drug to market. This novel way of helping people whose needs have not been met by for-profit pharmaceutical companies is gaining traction. Several partnerships are working to develop drugs to fight neglected diseases, underwritten by the Bill and Melinda Gates Foundation, Doctors Without Borders and other groups. Another nonprofit agency, the Aeras Global TB Vaccine Foundation, is searching for a means to prevent tuberculosis. For its first project, the San Francisco charity, the Institute for OneWorld Health, focused on reclaiming the all but abandoned drug, paromomycin, which research found promising in the 1960s. That was the easy part. Its hurdles lay elsewhere. The Internal Revenue Service at first denied the charity nonprofit status, concerned that it looked too much like a for-profit enterprise. The World Health Organization, which controlled the drug, was reluctant to hand over the data needed for further development. And OneWorld Health had to set up clinical trials matching United States and European standards in one of the poorest parts of the world. Nor was it obvious where the money would come from. The idea of a nonprofit drug company struck many as folly when Dr. Victoria Hale, a former Genentech executive and Food and Drug Administration official, founded OneWorld Health in 2001. So Dr. Hale and her husband started the project using their own money, though they have since won support from the Gates foundation, among others. My colleagues and mentors in the pharmaceuticals industry told me it was a wild idea, that it would never work out, that I was jeopardizing my reputation, Dr. Hale said. I started this organization knowing our first project had to be a winner or we wouldnt survive. An Ambitious Goal Dr. Hale hopes to stamp out black fever eventually, a goal that many doctors regard as impossible. The last disease we truly eradicated was smallpox, she said. Theres no urgency to eradicating diseases anymore. Why not? Black fever is the second-largest parasitic killer in the world after malaria. It is spread by sand flies, and Banthu, the squalid village about an hours drive from here that Mrs. Devi calls home, is an ideal breeding ground for them. The flies multiply in the cow dung that Mrs. Devi uses as fuel for cooking. They relish the sap in the banana groves and bamboo stands, and they thrive in the thatch used to make the tiny houses. Flies that have bitten infected humans transmit the disease when they bite another person. Smaller than mosquitoes, they can pass through most netting. Roughly 90 percent of black fever cases worldwide are found here in Bihar State in India and in Bangladesh, Nepal, Sudan and northeastern Brazil. Mrs. Devis daughter was the first in the family to contract the disease, and she died from it. Then Mrs. Devis youngest son, Rajesh, got it, and she brought him to the Rajendra Memorial Research Institute of Medical Science here, where he was treated and recovered. Now she, too, is receiving treatment. It is at the Rajendra Institute, a government research facility, that OneWorld Health set up one of the trials needed to make paromomycin widely available. Many Early Battles Dr. Hale first set her sights on the drug after she attended a conference in Belgium in 1999, where Dr. Shyam Sundar, an expert on black fever, was railing against the worlds failure to fight the disease. The tragedy, maybe even the crime, is that we have known that this drug is an effective treatment for kala azar since the 1960s, said Dr. Sundar, whose free clinic in Muzaffarpur was also a site for a trial by OneWorld Health. We could do something, but we were choosing not to. After visiting Dr. Sundars clinic in 2000, Dr. Hale, who was doing consulting work at the time, hired a law firm to help her get the tax exemption necessary to create a nonprofit drug company. The I.R.S. turned her down three times over 10 months, suspicious that her plan was a scheme by the drug industry to shelter profits. The tax agency challenged her to find an example of an existing charity that mirrored a for-profit business. It took me five days, and then at dinner, it hit me: N.P.R. and public television, she said. They look an awful lot like for-profit radio and television, but they serve a different audience with programs that their for-profit counterparts dont provide because they cant profit from them. Two weeks later, OneWorld Health received I.R.S. approval and set out to tackle black fever. The immediate challenge was financing. For a time, OneWorld Health survived on the largesse of Dr. Hale and her husband, Dr. Ahvie Herskowitz. They put up $100,000, signed a $315,000 promissory note, used the ground floor of their house as offices, and worked without pay for two years. The Gates foundation, which at the time was primarily underwriting vaccines and other preventive strategies, eventually offered a grant of $4.2 million that grew to $47.2 million for the development of paromomycin. Dr. Hale also got help from others, including the Skoll Foundation, which has provided financing to underwrite salaries for new senior executives. An Abandoned Drug An initial, formal test of paromomycin, an antibiotic sold in some countries as an oral treatment for diarrhea and as a topical treatment for cutaneous leishmaniasis, which causes lesions, was done in the late 1980s in Africa, two decades after it was identified as a simple, cheap, effective cure for black fever. Through a series of company mergers it was consigned to the corporate shelf and forgotten, ending up with the World Health Organization, which lacked the money to develop it beyond the Phase II clinical trials. But negotiations with the World Health Organization to hand over the data that would allow OneWorld Health to organize the Phase III clinical trials necessary for regulatory approval dragged on for almost two years. At the time, the W.H.O was developing another drug for black fever with Zentaris, a large pharmaceutical company, and the Indian government. That drug, miltefosine, has the advantage of being an oral treatment, while paromomycin is administered by injection. But miltefosine, an anticancer drug, also has drawbacks. In trials, it caused gastrointestinal problems in one-third of the patients. And patients must be strictly supervised to ensure that they take the full 21-day course of treatment and that women of child-bearing age are using birth control. By contrast, paromomycin has shown almost no side effects in trials. With a price of $100 to $200 a treatment, miltefosine is out of reach for most patients and government purchasing programs. Dr. T. K. Jha, a specialist in black fever who oversaw one of the OneWorld Health trials, said the W.H.O. wanted to make sure miltefosine made it onto the market before handing over its data on paromomycin. Commerce got in the way, Dr. Jha said. But Dr. Robert G. Ridley, director of the W.H.O.s special program for research and training in tropical diseases, disputed that. Dr. Ridley wrote in an e-mail message that the time lag had to do with getting financing from the Gates foundation and the process of negotiating an agreement with OneWorld Health. The subject of the commercial aspects of drugs is a difficult one for OneWorld Health, which is careful to avoid criticism of its for-profit cousins, as well as competition with them. We look a lot like each other, Dr. Herskowitz said. But we fill a gap pharma companies cannot because they have to make a profit. But given the choice of paying more than $100 for Zentariss miltefosine or $10 for paromomycin, governments and most patients will no doubt choose the cheaper drug. OneWorld Health does not intend to gain income from the drug. It has given a license to Gland Pharma, an Indian drug company that has agreed to manufacture the drug and sell it at cost when it is approved. But Dr. Hale can foresee a time when, say, a drug OneWorld Health hopes to develop to treat childhood diarrhea could be sold to travelers by a for-profit drug maker in exchange for royalties that would help sustain her organizations charitable work. Still More Difficulties Approval of paromomycin will not end OneWorld Healths challenges. Distribution looms as the next hurdle. In Patepur, a somewhat more prosperous village than Mrs. Devis, Dr. Syed Misbah Hassan, a clinical research coordinator for OneWorld Health, diagnosed kala azar in one boy after another. Dilip Manjhi, who is about 15, lay listless on a string bed as Dr. Hassan examined his abdomen for the telltale signs of the disease, a swollen spleen and liver. Dilips spleen extended eight centimeters below his rib cage and was rock hard. His liver protruded three centimeters below his ribs. Getting paromomycin to remote villages like Patepur at the end of pothole-pocked roads will be difficult. Dr. Hale is trying to enlist a British nonprofit group, Riders for Health, to help. The group uses motorcycles to connect poor people to medical services. In Zimbabwe, for instance, it has taken pregnant women in need of Caesarean sections to hospitals. My thinking, Dr. Hale said, is that we could equip a motorcycle with a cooler to transport the drug and equip the driver to give the injections and maintain records. But first, the Bihar State government and Indias central government must create a system that encompasses diagnosing the disease, buying and administering the drug, keeping records and spraying to reduce the sand fly population. Some experts wonder whether the government has the will to create such a system, when hundreds of thousands of Indian children die each year of measles, which can be prevented with a 15-cent vaccine. But Dr. C. P. Thakur, a former Indian health minister who oversaw a OneWorld Health trial of paromomycin, noted that black fever was one of five insect-borne diseases the Indian government had pledged to eliminate. India has also signed an agreement with the governments of Nepal and Bangladesh to eradicate the disease, and the Bihar State government has shown a willingness to work with OneWorld Health. The government will be the biggest challenge, Dr. Thakur said. But I believe the opportunities to end this disease have never been better, and also that the governments will has never been stronger. ================================ George Antunes, Political Science Dept University of Houston; Houston, TX 77204 Voice: 713-743-3923 Fax: 713-743-3927 antunes at uh dot edu Reply with a "Thank you" if you liked this post. _____________________________ MEDIANEWS mailing list [email protected] To unsubscribe send an email to: [EMAIL PROTECTED]
