Launch sequencing of pharmaceuticals with multiple therapeutic indications: evidence from seven countries

Abstract

Background New medicines are increasingly being identified as efficacious across multiple indications. The impact of current pricing and reimbursement policies on launch decisions across these indications remains unclear. Objective This paper, first, maps marketing authorisation and HTA coverage recommendation sequences of multi-indication medicines across Germany, France, England, Scotland, Canada, Australia, and the USA, and, second, evaluates the clinical characteristics, clinical development time and coverage recommendation time of multi-indication medicines, drawing comparisons between the first and subsequent indications of an approved molecule. Methods Medicine approvals by the Food and Drug Administration between 2009–2019 were screened to identify multi-indication products with approved oncology indications. Data on clinical trial characteristics, clinical performance and HTA outcomes were extracted from publicly available regulatory approval and HTA reports. Results Relative to subsequent indications, first indications were more likely to receive conditional marketing authorisation, have an orphan designation, have a single arm phase II pivotal trial and lower MCBS score. Subsequent indications had faster HTA coverage recommendation times in England and Canada. While the majority of first indications received HTA coverage recommendations across all settings, the proportion of subsequent indications with HTA coverage recommendations was lower and uptake varied considerably across settings. Conclusions Discordance in the value of first versus subsequent indications can pose major challenges in systems that define price based on the initial indication. Current pricing and reimbursement systems generate significant fragmentation in the approval and availability of multi-indication products across settings.

Timely, Cheap, or Risk-Free? The Effect of Regulation on the Price and Availability of New Drugs

“…For example, this could be the strategy pursued by the producer of pembrolizumab to enter the market for oncological drugs without direct competition with nivolumab [82]; a similar strategy might have been put forth by the producers keytruda, an immuno-oncological drug [21]. It also turns out that personalisation is the optimal strategy for the entrant rather than the incumbent, a result in line with the empirical evidence [75]. There may also be a trade-off between access and personalisation.…”

“…Finally, when there are large differences in cost effectiveness among patients treated with the same active principle, the literature proposes the use of indication-based prices (IVBPs), where the price may be indication-specific [ 22 , 24 , 25 , 47 , 53 , 72 , 73 , 74 ]. The use of IBP stems from the observation that some active principles used to treat cancer are listed for so many indications [ 72 , 75 , 76 , 77 ] that a single price may not be appropriate.…”

The impact of willingness-to-pay threshold on price reduction recommendations for oncology drugs: a review of assessments conducted by the Canadian Agency for Drugs and Technologies in Health

“…Mills et al looked at the launch sequencing of drugs with multiple indications in seven countries and noted that HTA coverage recommendations tend to be quicker for subsequent indications of the drugs when compared with the first indication for the drug. They speculated that this could be due to more robust clinical trial designs in the subsequent indication submissions and also first indications generally face higher barriers to entry [ 108 ]. Also, another aspect to be considered regarding quicker access to new cancer drugs is the expedited approval by regulatory agencies.…”

Special FDA designations for drug development: orphan, fast track, accelerated approval, priority review, and breakthrough therapy

“…In 2019, seven of the top ten grossing drugs were commercialized for an orphan and a non-orphan indication. Particularly drugs that are first approved for their orphan indications and then extend their marketing authorization to non-orphan indications ("orphan-first strategy") are criticized for benefiting from high orphan price premiums [72][73][74]. Scholars proposed patient (e.g., < 200,000 US inhabitants) or revenue thresholds (e.g., < $200 million), indication-specific pricing, and indication-specific formularies to control the usage and expenditure on partial orphan drugs [68][69][70][71].…”