Perspectivas de la industria farmacéutica en el patrocinio y financiación de estudios clínicos Jorge Pignataro Otman TALLER INTERNACIONAL SOBRE ENSAYOS CLÍNICOS SIMPOSIO “BARRERAS PARA LA INVESTIGACIÓN CLÍNICA EN AMÉRICA LATINA” 24 al 26 de marzo de 2011 - Conrad Resort Hotel - Punta del Este

Estudios clínicos en el ciclo de vida de un medicamento $

Entorno regulatorio cada vez más estricto El número de aprobaciones de nuevas moléculas por FDA 2010, demuestra el estado crítico de caída de la productividad. $Billions Source: US FDA’s Center for Drug Evaluation and Research and Drugs@FDA. Graph represents NME and BLA approvals by year. Source: PhRMA Statistics

La tasa de éxito es baja El modelo tradicional de desarrollo clínico debe cambiar porque el largo proceso de lanzar un nuevo medicamento se transformó en una proposición insostenible para la industria Phase 2 Pre-clinical Phase 1 Phase 3 Launch *R&D Spending by Research-Based Pharmaceutical Companies Fuente: Parexel’s Bio/Pharmaceutical R&D Statistical Sourcebook 2009/2010

3/24/2017 El desarrollo biofarmacéutico está liderado por los tratamientos para el cáncer Fuente : PhRMA 2010

Las “…ómicas” han influido en el diseño de las plataformas de Inv Las “…ómicas” han influido en el diseño de las plataformas de Inv. Clínica March 14, 2011 Study suggests long-term tamoxifen use reduces breast cancer deaths, medical costs Last Updated:March 14, 2011 17:14 Study results published Monday in the journal Cancer suggests that for certain women at an increased risk of breast cancer, tamoxifen can protect against the disease for a decade after treatment ends. March 21, 2011 Roche, Curis drug vismodegib meets goal of mid-stage skin cancer trial Last Updated:March 21, 2011 16:59 In the ERIVANCE BCC trial, 104 patients with advanced basal cell carcinoma received the Hedgehog Pathway Inhibitor once daily until disease progression. Results showed that vismodegib shrank tumours in a predefined percentage of patients in the study.

Oportunidades para el desarrollo de estudios clínicos en LA O.M.S. April 2010 E.M.A. Nov. 2010 F.D.A. (2011 ?) ANVISA Mar 2011 $ S.B.P.s C.E.R. Estudios Fases I - III C.E.R. : Comparative Effectiveness Research S.B.P.s : Similar Biotherapeutic Products

Algunas conclusiones La inversión en investigación clínica en Oncología alcanza aproximadamente el 20% del total de la inversión en I+D farmacéutica. Se estima el costo de desarrollo de un nuevo fármaco en 1.2 billones de dólares pero la preocupación de las empresas es como ser más eficientes, incrementando la seguridad, aportando diferencias tangibles, reduciendo costos y tiempo al mercado. Latinoamérica ha avanzado en la mejora de marcos regulatorios y recursos humanos, con ventajas competitivas frente a países emergentes (China) y Europa Oriental. Surgen nuevas áreas de diseño de estudios clínicos dentro del ciclo de vida de un medicamento que son especialmente atractivas para LA. Fuentes: PhRMA; DATAMONITOR, Spectrum, PharmaVenture

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Oncología requiere diseños de estudios clínicos de mayor complejidad

Increasing duration of clinical trials Evaluation of clinical trial duration by indication and phase of development, 2001–06 In 2002–04, the average time taken for a drug entering Phase I clinical trials to completing Phase III was 7.0 years, a rise of 1.2 years over calculations made in 1999–2001, in part driven by the heightening safety concerns of the FDA. The Agency’s advisory panel has recently recommended that the FDA demand additional cardiovascular testing for all new diabetes drugs, and that companies conduct long-term studies to rule out unacceptable cardiovascular risks for new diabetes compounds. Similar recommendations could conceivably be made across other therapy areas in the future, further prolonging clinical trial durations. Source: Datamonitor adapted from Pharmaprojects Pharmapredict (2006) 14 14

Growing size of clinical trials Numbers of enrollees by therapy area for Phase III clinical trials conducted in the US in 2007–08 The size of clinical trials is increasing due to the requirement for growing quantities of clinical data in response to more stringent regulatory scrutiny, and concerns over drug safety. In order to increase the power and potential statistical significance of a study, a larger number of enrollees are required. However, increasing patient recruitment is directly linked to study duration and cost. Drugs to treat cancer, cardiovascular disease, diabetes and endocrinology recruited a considerably larger number of enrollees than for the remaining therapy areas. This is likely to be attributed to the large patient populations within these therapy areas and therefore ease of recruitment of such patients. Source: Datamonitor adapted from Thomson Pharma (August 23 2008), Copyright Thomson Scientific 15 15

The cost of R&D is increasing The growing complexity of clinical trial protocols has resulted in patient recruitment rates dropping from 75% in 1999–2002 to 59% in 2002–06, while volunteer retention rates fell from 69% to 48% over the same period. Increasing the size, complexity and duration of clinical trials generates a greater volume of data, which increases the time and costs of data capture and analysis, as well as management of the clinical trial process. Clinical trials with a high degree of complexity are more costly, 2006 Source: Datamonitor adapted from Fast Track Systems (2006) 16 16

Clinical trial success rates are declining Evaluation of clinical trial to launch success rates by indication and phase, 2001–06 Pharma will have to become more astute when selecting which compounds to progress to Phase III development. This is further hampered by falling success rates for clinical trials. The success rates for drugs entering a clinical development stage (Phase I, II, and III) and progressing to actual launch has fallen by 23%, 20% and 11%, respectively (2001–06), an observation common to all individual indications analyzed and at every stage of clinical development. Source: Datamonitor adapted from Pharmaprojects Pharmapredict (2006) 17 17

Why Phase III drugs fail? Why Phase III drugs fail – therapy area analysis Approximately 58% of Phase III clinical trials are unsuccessful, with the primary cause for failure being the inability of the trial data to demonstrate efficacy of the tested product against placebo. Success, or rather failure of a Phase III trial is also dependent on the following two factors: whether a drug has an established or novel mechanism of action; whether trial endpoints are objective or subjective. Source: Datamonitor adapted from Why products fail in Phase III? (2006) 18 18