Combination tactics for orphan drug manufacturers

By Marc Botteman, Pharmerit

The number of new compounds in R&D with an orphan drug (OD) designation has steadily increased over the past decade. In 2000, only 12 compounds in R&D had received an OD designation by the EMA. But by 2009, that number had increased to 105. Overall, during that decade, 615 OD designations had been granted – yet, fewer than 10 percent of these agents received an authorisation over the same decade.

Success in bringing any drug to market is fraught with numerous challenges. However, regulators have tried to facilitate this process for ODs. For example, unlike other drugs, ODs are always authorised via the centralised European procedure. Moreover, due to the small number of patients with, and the severe or life-threatening nature of most orphan diseases, EMA authorisation can often be filed immediately after conducting phase II clinical trials rather than waiting for phase III results. However, one hurdle that has not been streamlined for OD is many countries’ requirement to demonstrate cost effectiveness for reimbursement.

Even in European countries where cost-effectiveness is not (yet) mandatory, the available cost-effectiveness evidence can help with pricing negotiations. Ironically, since many OD authorisations are based on limited data (i.e., small sample sizes for clinical trials and phase II study design), the body of evidence available to develop cost-effectiveness analyses at the time of market access is often incomplete. In addition, cost-effectiveness guidelines vary per country, resulting in the need to conduct analyses in each individual country for which market access is sought.

Besides clinical and health economic research, companies can conduct several types of strategic research that can help optimise the OD reimbursement process. First of all, landscape analyses help to identify the epidemiology and available drugs for the corresponding indication, their prices, safety and efficacy profiles and reimbursement status. Secondly, value messaging includes interviewing key opinion leaders to test the target product profile (TPP) and to identify most important value messages and unmet medical needs.

The utilisation of payer research should involve conducting interviews with local, regional and national payers to assess their perceptions regarding the TPPs (including price points) and value drivers. Identify requirements for OD market access and reimbursement and select comparators, data to be delivered and analyses to be conducted. Finally, initiate dialogue between regulatory and payer communities in order to align payer expectations with regulatory data.

For ODs, the timing of conducting this strategic research is critical given the relatively short authorisation time-frame. The same is true for health economic assessment. Hence, to optimise drug pricing and market access, strategic and health economic research should be conducted in tandem as early as possible.

There are also areas in which strategic research could benefit from health economic information. To begin with, optimise the output of strategic research by including early health information in TTPs tested during payer research. Quantifying the identified value drivers in monetary terms and testing at an early state of development the cost-effectiveness of the drug based on numerous pricing scenarios and TTPs will also play a pivotal role.

Another type of research increasingly conducted by pharmaceutical companies during drug development is trial simulation, which helps to minimise risks and guide decision-making by formalising assumptions and quantifying uncertainties about the drug and upcoming trials.  Trial simulations are especially valuable for ODs as there is often very limited data available due to the limited number of patients and comparisons mostly with placebo. This information could be used for registration but potentially also when designing subsequent trials, which might be a sine qua non condition to obtain preliminary approval and data necessary for reimbursement dossiers and pharmacoeconomic analyses. For instance, by imputing early clinical results in a health economic model, the optimal dose and best patient subgroup can also be identified to ensure the new drug’s cost-effectiveness.

With its international reach and multidisciplinary staff, including experts in OD regulations, payer research, market access and health economics, and trial simulation, Pharmerit’s mission—and passion—is to help manufacturers seamlessly integrate pricing/reimbursement and pharmacoeconomic evidence and strategies to ensure that patients have access to needed treatments.

Biography

Marc Botteman, co-founder of Pharmerit International in Bethesda, MD, has been conducting health economic, outcomes, market access, payer and pricing research for global sponsors since 1995 and has authored over 50 publications in peer-reviewed journals. He holds  a Master’s degrees in economics from Namur’s FUNDP, Belgium and demography, Georgetown University.