Access to antiviral stockpiles for pandemic use – an industry perspective Dr. David Reddy, Pandemic Influenza Taskforce Leader, F.Hoffmann-La Roche Ltd, Switzerland

Topics covered by this presentation Status update –Role of antivirals in a pandemic –Manufacturing capacity for influenza antivirals –Magnitude of existing Government pandemic stockpiles Strategy for balancing decline in government orders with need to maintain pandemic production capacity Addressing key outstanding issues –Ensuring rapid deployment of antiviral stockpiles –Policy for allocating antiviral stockpiles in a pandemic –Maintaining government antiviral stockpiles –Special populations

“Once a pandemic has been declared…the role of antiviral drugs is unquestionable” “Pending the availability of vaccines, antiviral drugs will be the principle medical intervention for reducing morbidity and mortality” “Stockpiling drugs in advance is presently the only way to ensure that sufficient supplies are available at the time of a pandemic.” Avian influenza: assessing the pandemic threat. WHO January 2005 Role of Antivirals in a Pandemic

Utility of antivirals (Tamiflu) in the management of human infection with a novel influenza virus (H5N1) Adapted from: Writing Committee of the Second World Health Organization Consultation. Update on Avian Influenza A (H5N1) Virus Infection in Humans. N Engl J Med 2008; 358; Survival (%) n =

Production capacity for antivirals has increased government orders have dramatically declined Production capacity now outstrips demand Roche has fulfilled orders from the governments of > 85 countries, accounting for ~225 million treatment courses Generic sub-licensees facing same issue

Sources: Media / National pandemic plans and GeoHive.com (as of May 2008) Government antiviral stockpiles are sufficient to cover only <5% of the world’s population

Strategy for balancing decline in government orders with need to maintain pandemic production capacity Adapt Tamiflu supply chain output in accordance with demand Maintain a buffer stock of intermediates and final active ingredient (oseltamivir) at company’s cost/risk Gearing up of production will be triggered by one of two events 1.Roche inventories drop below target levels 2.WHO declares pandemic phase 4 (human to human transmission) Communicate that surge production will not meet demand at the time of outbreak of a pandemic

Policy for allocating antiviral stockpiles in a pandemic Roche’s guiding principles Maximize benefit to society by supporting WHO’s and national governments´ pandemic efforts Balance the needs of Roche’s shareholders, employees and society as a whole Base decisions on the strength and integrity of the scientific and medical information available Communicate Roche’s approach in a transparent manner Maintain a dialogue with the WHO and other international agencies

Policy for allocating Tamiflu during a pandemic Phase IV – Focus on implementation of pandemic containment measures Deliver WHO Rapid Response Fulfill existing pandemic orders, from both governments and other groups Increase rapid response effort for containment Roche will suspend new corporate orders and normal retail sales until the requirements of the WHO and governments are met

Policy for allocating Tamiflu during a pandemic Phase V/VI – Containment measures have failed Continue to seek the input of WHO and international agencies/experts to provide maximum possible health benefit in the allocation of Tamiflu Where clear priorities for allocation cannot be developed and agreed upon, Roche will consider the “first come, first served” principle for fulfilling government orders

Tamiflu in the management of human H5N1 infection highlights importance of rapid intervention 1 / 1 6 / 16 4 / / / 15 4 / 5 5 / 7 1 / 12 Indonesia 1 Egypt 2 1. Adapted from Nyoman Kandun et al. Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series. The Lancet. Published online August 14th Adapted from Abdel-Nasser Abdel-Ghafar. Working On the Front Line with H5N1. Perspectives in Interpandemic Influenza, Madrid, Spain. 2007

Ensuring rapid deployment of antiviral stockpiles Rapid response and regional stockpiles established –Regular meetings between Roche and WHO logistics teams Roche & GSK recognize the role of the private sector in a pandemic for maintaining critical infrastructure –Providing information on potential impact of a pandemic on business continuity –Providing specific plans for corporations to purchase antivirals, and to help maintain antiviral stockpiles Many government plans still lack detailed information regarding allocation and delivery of antivirals and guidance for the private sector

Maintaining government antiviral stockpiles Options offered by Roche to governments Stability testing – Roche provides data and governments extend shelf life at own discretion Re-processing – developing method for re-claiming active drug from expiring government stockpiles Regulatory approval – shelf life extension for government pandemic stockpiles

Special Populations Children –Relenza approved in children ≥5 years –Tamiflu approved in children ≥1 year Pediatric dry suspension – 2 year shelf life 30 and 45 mg capsules recently approved (5-7 years shelf life) Extemporaneous preparation Development program in children <1 year ongoing Critically ill patients –Reduction in mortality with early administration of Tamiflu to H5N1- infected patients –Intravenous NAIs in development – oseltamivir, peramivir, zanamivir –Case series from Hanoi 1 reported that Tamiflu was well absorbed after nasogastric administration in 2 patients with severe H5N1 disease 1 Heiman FL Wertheim ISRVI 2008

Summary Experts agree continued planning for a pandemic is critical Antivirals will play a crucial role Stockpiling in advance is the only way to ensure that antivirals will be available at the start of a pandemic Pandemic preparedness requires co-ordinated multi- sectoral response Roche has developed strategies to maintain government pandemic stockpiles over time