5) Description of health product/service offering: OneWorld Health is focusing on 3 diseases of poverty at this time – VL (India and Horn of Africa), malaria (Subsaharan Africa and Asia, primarily), and secretory diarrhea (Asia, Africa and Latin America). Our most advanced project is VL. Visceral leishmaniasis (VL) is second only to malaria as a parasitic cause of mortality. Most of the 500,000 new cases of VL each year affect the rural and resource-poor populations of India, Bangladesh, Nepal, Sudan, and Brazil. In the Bihar state of India alone, 31 of 38 districts are currently in the grips of the disease. If left untreated, VL is nearly almost fatal.

Currently available drugs to treat VL are either toxic (antimonials, amphotericin B, pentamidine, miltefosine), prohibitively expensive (liposomal amphotericin B, miltefosine), or ineffective (antimonials, pentamidine). New therapies to treat the disease are urgently needed.

OneWorld Health has developed paromomycin as a new cure for visceral leishmaniasis. Paromomycin is an off-patent aminoglycoside antibiotic that was previously approved by the U.S. FDA and is still marketed in the U.S. as an oral formulation to treat intestinal parasites. Paromomycin is an old drug made new again, so it has great efficacy and no safety surprises.

In June 2003, OneWorld Health initiated the largest phase 3 clinical trial ever performed for VL, treating 667 VL patients in India. The clinical trial concluded in November 2004 and OneWorld Health is submitting an application to the Indian regulatory agency for review in June 2006.

Regulatory approval of paromomycin is the first step to a comprehensive Indian control and public health disease elimination strategy. OneWorld Health is in the planning stages for a Phase IV Pilot Access Program designed to expand access of paromomycin treatment for patients with VL, focusing on providing outpatient treatment in rural, resource-constrained settings in the Bihar region of India. The goal is to take VL treatment from the hospital to the village, and to demonstrate that public health impact on a large, rural scale is possible.

To construct an effective and sustainable delivery strategy, OneWorld Health is formalizing partnerships with local government, primary healthcare centers and nongovernmental organizations (NGOs). Under the leadership of OneWorld Health, the partners will conduct studies administering paromomycin in rural field conditions, to provide further data on the safety and efficacy of the drug.

6) Description of innovation: We will focus on the VL program because it is the most advanced one in our portfolio. VL affects only the poorest of the poor who live in rural areas. These regions are resource-constrained and lack any reasonable medical system to manage this fatal disease. While paromomycin can be used safely and effectively in urban specialty hospitals, access to this affordable treatment needs to be expanded to people in rural and resource-constrained areas where VL occurs. The objective of the Pilot Access Program is to expand patient access to paromomycin treatment for VL in rural and resource-constrained settings by providing local outpatient treatment and referral.

The VL program is unique because it combines a clinical drug development program with a public health component through a large-scale disease elimination program.

7) Operational model: The Pilot Access Program seeks to provide lower cost, effective treatment for VL with paromomycin as outpatient therapy in resource-constrained settings. A gradual roll-out of delivering treatment into resource-constrained areas is planned, allowing for consistent, continued protection of patient safety, and helping to avoid development of drug resistance.

The program will expand access, and the delivery system by adding the capacity to provide this newly-established outpatient treatment for the first time in resource-constrained settings closer to the homes of subjects.

The ultimate goal of the project will be the safe provision of appropriate, affordable treatment close to the patient’s home, reducing or eliminating the need for the subject to travel long distances for treatment and to be admitted for a lengthy inpatient hospital stay.

8) Human resources: OneWorld Health will manage this project with its internal scientific, regulatory, and public health staff, who possess expertise in drug development process and assessment, monitoring and evaluation. They are also responsible for designing and overseeing all clinical studies and compilation of regulatory approval documents. OneWorld Health will outsource clinical monitoring and manufacturing to local partners.

Human Resources in India:

Kala-Azar Centers of Excellence: Based on their prior experience with VL and their previous involvement in the Phase 3 paromomycin trial and currently involvement in the clinical label change/expansion study for paromomycin, the principal investigators and their centers will play a key role in this Pilot Program. The principal investigators will train and advise other participating healthcare practitioners. The centers will be the referral centers for severe cases of VL or for patients with treatment-related severe adverse events who require higher levels of care, and they will provide second-line treatment to subjects who relapse or do not respond to paromomycin treatment. Four principal investigators (MDs), each with a staff of 25, with a total of approximately 100.

Government of India/Bihar: Final site selection for the participating government sites will be made in conjunction with the appropriate GoI authorities.

Nongovernment Organizations: The Janani Franchise system consists of two separate levels of service delivery. Surya Clinics are urban-based formal medical centers with full-time medical doctor on staff and Titli Centers, are the rural, village-level, non-medical healthcare facilities where the staff has had no formal medical training. Hundreds of Titli centers in Bihar; dozens of Surya medical clinics.

9) Key operational partnerships: OneWorld Health has decided, after careful evaluation during our work in Bihar for several years, that the government alone cannot be relied upon to deliver VL cures. The private system is capable in some urban areas, but has limited capacity and is absent in rural settings, where the majority of patients live. So IOWH is pioneering a distribution system with a social marketing agency that is very highly respected in Bihar.

Janani operates an innovative, health services delivery and management system which includes healthcare workers and facilities at all levels. Janani, along with the Government of India, will be key implementing partners for the Pilot Access Program. But a disease elimination program cannot occur without the partnership of the Government of India. So we will also partner with GoI to make this program receive national funding, World Bank funding, and have accountability to the Government and Bank.

Overall, the design of the Pilot Access Program promotes technical, institutional and operational capacity-building in Bihar, in both the public and private sectors. The design also builds upon the current system—the Surya Clinics (SC) and Titli Centers (TC) within the Janani franchise system are presently highly respected for the delivery of reproductive health services for both men and women, for their innovative management and delivery systems, and their community education and awareness experience. However, Janani facilities do not currently provide VL diagnosis or treatment services. The Pilot Access Program provides an opportunity to expand services by responding to this lack of VL experience. The design will enable a slow ramp-up with sufficient time for training, supervision and assessment and with increasing levels of involvement and responsibility.

10) Financial Sustainability

          • Fees charged to clients?: Yes

          • How do you assure affordability?: We have been strongly advised to not make this program totally free to people – that people will not value it (Muhammad Yunus and others). We believe that a small cost should be applied (a few dollars?), but the Government of India will make this decision.

          • Earned incomes as a percentage of operating costs: N/A

          • Other funding sources: The program, as it was originally negotiated, brings no funding to OneWorld Health – it is our first new drug program and its value is proof that IOWH can develop a new medicine and get it to poor people in rural settings. All other IOWH programs bring some revenue back to IOWH through tiered pricing sales in urban settings.

The Pilot Access Program itself is funded by a US$30 million grant from the Bill & Melinda Gates Foundation. The comprehensive control and public health disease elimination program will be financed through a collaboration between international donor agencies (World Bank) and the Government of India with implementation through local government health infrastructure and the integration of established local non-governmental organizations with expertise in rural healthcare provision.

          • Strategy for long-term sustainability: World Bank funding, Government of India commitment and engagement.

11) Current and Future Impact

          • Total number of clients: 700 patients in clinical trials to date and 1200 in next large phase IV trial.

          • Clients in the past year: 700 in clinical trial

          • Percentage of low-income clients: 100%

          • Impact: To better ensure effective treatment, subject safety, and expanded access, the Pilot Access Program includes extensive training programs for health care providers, rural healthcare workers, and the population at risk. The training and education will not only respond to the needs of this Pilot Program, but also will be a valuable contribution to the overall Indian visceral leishmaniasis control strategy by contributing to the health workforce with experience in VL diagnosis using new diagnostic tools, paromomycin treatment, and increasing community understanding and awareness of VL.

The Pilot Access Program assumes that intense levels of education and awareness for both doctors and villagers (a Janani expertise) will begin as early as possible. Moreover, the design allows Janani, the Government PHCs and medical colleges, and relevant labs to become integrated and involved at a pace they can manage. Sustainable capacity-building, as is crucial for any large-scale roll-out, will be implemented and assessed throughout this Program.

          • Overall "market": Leishmaniasis is a parasitic disease currently affecting some 12 million people in 88 countries, primarily in the developing world. Up to 350 million people are at risk of infection due to transmission of the parasite by its vector, the sand fly, small biting insects which breed in moist soil, forest areas, caves or the burrows of rodents, and feed from infected animal reservoir hosts or humans. Visceral leishmaniasis (VL) is the most serious form is nearly always fatal if left untreated.

In Eastern India, all districts of Bihar and regions of Jharkhand, West Bengal and Uttar Pradesh are facing the worst VL epidemic since the late 1970s. On the order of 200,000 - 250,000 people are believed to have contracted the disease in 1993 (five times the official figures), and because of the rapid spread, an alarming situation exists (Desjeux 1996). It has been estimated that 80% of the global burden of VL is present in the Indian continent. Epidemics of VL do also occur elsewhere, for example in southern and eastern Sudan. Currently, the risk of epidemics exists continually in the Horn of Africa, at the junction of Eritrea, Ethiopia, and Sudan, an area highly endemic for many years where tens of thousands of refugees, returnees and agricultural workers have been resettled.

12) Scaling up strategy

          • Stage of the initiative: Start Up stage.

          • Expansion plan: The overall goal of the Phase IV Pilot Access Project is to expand patient access in resource-constrained settings to paromomycin injection treatment for VL by providing appropriate referral and outpatient treatment systems.

The Pilot Project is set up into three modules and has a staggered roll-out to ensure control for safety and appropriate training of all health care workers involved, with approximately 1000 patients total included in all three modules (more patients in first module, progressively less in last two modules). The first module seeks to expand access while continuing to assess the safety and efficacy of paromomycin injection in an outpatient setting. The second module seeks to expand the outpatient network and incorporate village referrals. The third module seeks to expand treatment and referral network to more resource constrained settings. This Project will also form part of the Government of India’s National Vector Borne Disease Control Program.

13) Policy change: VL is a disease of poverty, and affects the poorest populations in rural, resource-poor parts of India. The Government of India’s National Vector Borne Disease Control Program will help to drive real public health and social policy impact through this massive disease elimination program. OneWorld Health works locally in collaboration with local governmental (Indian government) and nongovernmental partners (World Bank) and local manufacturers to deliver the drug to the people who need it most. Until now, this type of model that combines clinical drug development with drug delivery and public health intervention has not been attempted.

14) Origin of the initiative: Fueled by a growing recognition of global health inequities, pharmaceutical scientist Dr. Victoria Hale spent the late 1990s trying to envision how pharmaceutical science could most impact the lives of millions suffering from infectious diseases in the developing world. New medicines for most tropical infectious diseases did not exist, and older therapies, if they were available, were often toxic, difficult to use, or increasingly ineffective due to drug resistance. Supported by a group of dedicated and resourceful pharmaceutical peers, Dr. Hale led a worldwide effort to uncover potential new medicines for diseases of poverty and pursue their research and development. In July of 2000, Dr. Hale founded the Institute for OneWorld Health, the first nonprofit pharmaceutical company in the United States. Its mission was to develop safe, effective, and affordable new medicines for those most in need. Our mission is the identification and development of affordable new medicines to treat parasitic and other neglected infectious diseases in the developing world.

Contact Information:
Seemin  Pasha
Ashoka Fellow
Director of Executive Operations
Institute for OneWorld Health
(NGO)
50 California Street, Suite 500, San Francisco, California 94111
United States
Tel: 415-421-4700, ext. 422
Fax: 415.421.4747
Email: spasha@oneworldhealth.org
Website: www.oneworldhealth.org