Are Canadians Missing out on Innovative Medicines?

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 A review of the approvals for New Active Substances and Biologicals in Canada and the US has identified that the gap between new drugs (New Active Substances, NAS) available in the US and those available to Canadians could be widening.  Multinational companies have been consistent in delivering relative equity in the NAS availability between the US and Canada.  The difference seems to be increasing with those NAS whose submissions are sponsored by US based companies that do not have a presence in Canada. A comparison of these types of approvals in the US between a three-year period (2014-2016) and 2018 shows a 250% increase. This shift illustrates an immediate opportunity for partnering with these companies and reducing the gap in the availability of new medicines between Canada and the US. There are currently 84 NAS approved by the FDA that have yet to be approved by Health Canada and 60% of them were approved more than a year ago. This creates a uniquely Canadian opportunity for companies who have an infrastructure in Canada and are looking to expand their portfolios. 

 There is a relatively new phenomenon called FOMO. (Fear of missing out). It is generally thought to be an effect of social media, but recently the latest report from the Patented Medicine Prices Review Board (PMPRB) and The National Prescription Drug Utilization Information System (NPDUIS) has pulled on this emotional thread. They reported in “Med Entry Watch 2017” that only 48% of New Active Substances (NAS) approved in the US & EU are approved in Canada. An analysis of the Notices of Compliance (Health Canada’s (HC) issuance of marketing authorization) and the US Food and Drug Administration’s (FDA) approvals lead to similar conclusions.  There are some nuances that suggest the situation is not that dire and that a greater effort to work with US companies to bring valuable medicines to Canada might be increasingly beneficial to Canadians and the pharmaceutical companies that bring them those medicines.

Globalization has been an ongoing pursuit in industry for decades and the pharmaceutical / biotech industry is no different. Multinationals want to have consistent portfolios across their territories to limit the risks and optimize their efforts. This makes sense and it's working.  Looking at the data from a Canadian perspective, 94% of NAS approved by Health Canada were also approved in the US.  84% of these medicines were to the same company or a subsidiary. The reverse perspective of looking at approvals from outside Canada and of looking in, gives a much different story.  When the timeframe is limited, there is a suggestion Canada is being left out. The Canadian pharmaceutical landscape is not identical to that of the US or the EU, as it is highly regulated from a pricing and reimbursement perspective and it is much smaller in terms of number of patients and limited access. These factors might not be enough to deter global healthcare companies from seeking approvals in Canada but how do these factors impact the decisions of smaller national companies developing medicines for their own populations?

Will we see more alignment between which NAS are approved in Canada versus the US and EU or less?  With a change in how drugs are being developed, is there a growing trend or will the status quo remain? Given that “slightly less than half of all New Products in the US and the EU” make it to Canada should we be worried? This paper is an analysis of the data with the hope that in the end, a match can be made between products not coming to Canadians and companies able to facilitate them.

 To identify if there is any commonality in those products which are not approved in Canada but were approved in the US by the FDA. Secondarily to identify any trends with respect to this commonality. 

Data was taken from the Health Canada Notices of Compliance website including all approvals for New Active Substances, Priority Submissions, Priority New Active Substances, Biological New Active Substances, Biological Priority and Biological New Active Substance Priority for the years 2014 to February 2019. These uniquely defined terms on the HC website are hereafter referred to collectively as New Active Substances or NAS. Data was also retrieved for earlier dates for products approved in the US that did not fall into this timeframe. Similarly, approvals from the FDA were downloaded from the FDA website on all NASs during the period 2014-2018. The FDA website was also searched for products when the Canadian NAS didn’t match the FDA data. A review of the Patented Medicines Pricing Review Board (PMPRB) publication “Med Entry Watch 2017” was also undertaken to identify similarities and differences from the publication as it was released within a close timeframe of the work.   The PMPRB is a Canadian government agency working in the field of pharmaceutical evaluations.

 Companies that have a presence in at least Canada and the US seem to be the most successful in gaining approvals for NAS between these two countries (Figure 1). One would expect that multinationals are effective at working with multiple government agencies at the same time to attempt relatively concurrent approvals. Generally, there is a coordinated approach to the health authorities, local and global resources working in concert to ensure timely communication and filings . 

 When the same company seeks approval for a NAS in both Canada and the US and the NAS is approved, Canada follows the US within 1 year, 66% of the time (Figure 2).  When the looking at FDA approved NAS, where the US company sponsor doesn’t have a Canada affiliate or subsidiary, the delay is on average 19 months (Figure 3), or 12 months longer than the average approval time of 7 months when the Company entity exists in both countries. There are many possible reasons why this is the case, not the least of which is that companies without a presence in Canada are not focused on submitting their dossier to Health Canada.   

 57% of the NAS approved in the US in the past 5 years have been approved in Canada (Figure 4). Of the ones that haven’t, 63% are for companies that do not have a presence in Canada. As one might expect, the proportion of NAS approved between the two countries goes up over time.  By limiting the timeframe to NAS approved by the FDA before Q2 2017 and considering NAS approved by HC until Feb 2019, then the number of NAS approved by HC increases to 71%.  

What of the 43% of NAS not yet approved? It turns out that 63% of those NAS' are for companies without a presence in Canada. The story doesn’t end there though, so far, the focus has been on data reported on an average over the last 5 years. A more in-depth analysis reveals a striking potential evolution in the US that could negatively impact Canada.

 With the success of small pharma and biotech companies in the US there has been a drive for some companies to hold onto their potentially successful NAS and either wait for licensing and partnership with multinational pharmaceutical companies or proceed to approval on their own. The trend suggests a change in the types of sponsors who are gaining approval for NAS in the US. What is striking is that there is a 250% increase in US only approved NAS in 2018 relative to the average over a three-year period 2014-2016. (Figure 5).

There is an increase in the number of new medicines approved in the US to companies that don’t have a presence Canada. With a global focus that does not necessarily put Canada as a priority for these companies, an increase in effort will likely be needed to ensure valuable innovative medicines reach Canadians in a timely manner. Globalization on the other hand by larger pharmaceutical companies is centralizing business development efforts and de-emphasizing regional priorities in favour of global ones. This leaves a tremendous opportunity for smaller companies, or multinational companies with a freedom to act regionally to fill the gap and to help bring valuable medicines to Canadians that might otherwise not make it here. Whether evaluating differences between countries and the approvals or the availability of medicines, the fear of missing out can lead to conclusions based on bias and assumptions. There is value in a solution which closes the gap and that leads to the better health for Canadians.