In Vivo: 医療用医薬品・医療機器産業の経営層向けニュース
By Deanna Kamienski 06 May 2021
During Q1, biopharma merger and acquisition value reached $34.8bn and drew in $35bn in potential deal value (PDV) from alliances...
Biotech and pharma’s response to the COVID-19 pandemic has been nothing short of exceptional. While rapid repurposing efforts have yielded relatively few solutions, innovative R&D has produced multiple therapeutics and vaccines across different classes, all within 12 months of the novel coronavirus first being identified. With the whole world affected by COVID-19, the biopharma sector is seeing more public interest and engagement than ever before.
This now leaves the industry in the challenging position of sustaining this positive momentum. There are undoubtedly lessons from pandemic successes when it comes to wider best practice in R&D, and these should be celebrated and adopted where possible. This article discusses three general areas as a starting point: the pace of R&D, clinical trial diversity, and the profitable legacy of pandemic investments.
One year on from the World Health Organization declaring COVID-19 a global pandemic on 11 March 2020, editors across Informa Pharma Intelligence publications are taking a closer look at its impact and possible lasting implications for the biopharma and medtech industry.
However strong the temptation to rewrite the rulebook completely, there are many more actions that were uniquely enabled by the pandemic that are simply impossible in usual times from an ethical, regulatory or commercial standpoint. It is in the communication of these nuances where any positive long-term reputational legacy from the pandemic will lie. Get it wrong, and the industry will face a whole new set of criticisms from a newly engaged and better-informed consumer base. Once you have shown that it is possible to develop new drugs within 12 months, how do you go back?
“Less haste more speed” is a common admonishment, thankfully proven to be entirely wrong in the case of coronavirus vaccine development. Innovative biotechs such as Moderna, Inc., BioNTech SE and Novavax threw caution to the wind and stand to be rewarded handsomely, while the traditional big vaccine players have languished. Merck & Co.’s failure in Phase I was as much due to its vaccine platform as its reluctance to embrace urgency and a flexible mindset in the speed of R&D. Even if its early-stage clinical trials did show sufficient immunogenicity, cautious development meant that any meaningful supply would have come too late to have a substantial effect on global recovery. While Sanofi CEO Paul Hudson said in a recent interview with Barron’s that the French pharma is taking a conservative stance in downplaying the potential of mRNA technology in the flu vaccine setting. Considering how rapidly novel vaccines can now be developed, Sanofi’s stance may need to evolve quickly.
This conservatism of incumbents is tied to many decades of experience in R&D. A recently published study by BIO, Pharma Intelligence, and QLS Advisors revealed that the old commonly cited benchmarks around clinical development success rates and timelines still hold true. As shown below, the likelihood of approval for a new drug entering Phase I trials remains stubbornly low at 7.9%, while the mean drug development program requires 10.5 years to successfully navigate through every clinical and regulatory hurdle.
The reconciliation between past (10-year timelines) and present COVID-19 reality (1 year) requires deeper levels of understanding than can be expected of the public. There have been ample well-meaning commentators suggesting that rapid development is the new normal. This misses the point that such timelines require the convergence of many different factors that will never all be present at the same time again. This includes:
Incredible investment landscape, both direct spend and indirect platform development enabling running start
Pressure and engagement within multiple stakeholders, including industry, governments, regulators, NGOs and the public
Re-writing of the regulatory rulebook, enabling INDs, clinical trials and regulatory reviews at record pace
Good fortune, as unproven technologies yielded 90%+ efficacy with excellent safety
Part of the solution lies in public education of the rigor of conventional R&D, all of which is done within a painstakingly strict regulatory framework. While drug programs may seem slow moving, each calculated step is being done with patient interest uppermost. Yet industry must also be compelled to modernize where possible, with a large debt of gratitude owed to the hundreds of thousands of volunteers that helped to accelerate COVID-19 research. There are key lessons around disease-agnostic platform development, clinical trial design, patient recruitment and public engagement that must be adopted into best practice. The solution must therefore be two-fold: improve upon historical 10-year average timelines while also retaining and communicating the rigor that protects patient wellbeing. Whether incremental improvements in the pace of R&D is enough to sustain a halo effect remains to be seen, but the industry must also be seen to be trying.
The lack of minority representation within trials is a long-standing issue. Despite years of effort, a lack of authority by the US FDA means that proposed standards and guidance documents amount only to encouragement and not enforcement.
Accordingly, trial sponsors have largely failed to self-regulate, resulting in study populations that are not wholly representative of real-world patient demographics. Analysis by the Tufts Center for the Study of Drug Discovery, described in Exhibit 2, shows the overrepresentation of males, and stark underrepresentation of black participants, or participants of African descent in US trials. Disparities in the expected number of Hispanic or Latino volunteers, and the “Other” category comprising of Native American, Native Alaskan, and Hawai’ian or Pacific Islander participants, were also notable. Data were gathered by comparing reporting of patient subgroups in clinical trials submitted as part of NDAs or BLAs over the 2007–17 period to the expected enrolment based purely on epidemiology and census data. With participant subgroup reporting optional, these disparity calculations may even be underestimates of the true picture.
The Black Lives Matter movement has shone a spotlight on the many faces of discrimination, triggering long-overdue introspection and action within the clinical trial community. This can also be seen through the lens of the pandemic, where health and economic outcomes for minority groups are consistently poorer and existing inequalities have been exacerbated. In the early stages of COVID-19 research, the NIAID-funded ACTT platform trial was criticized for failing to adequately enroll black Americans, despite this demographic bearing a disproportionate number of cases.
As research pivoted toward vaccine development, the medical community expressed concern that repeat performances would promote vaccine hesitancy among patient groups that were also at the highest risk. To the credit of Pfizer Inc. and Moderna, the two pioneering mRNA vaccine developers that were the first to enroll large Phase III trials in the US, diversity was prioritized at the expense of overall recruitment speed. Both companies committed to weekly enrolment updates, including transparent assessments of the proportion of volunteers from diverse backgrounds. The final minority representation within their trials was 41.4% (Pfizer) and 37.0% (Moderna). In particular, Moderna essentially closed recruitment to white participants in later weeks in order to achieve this diversity, as traditional patient acquisition channels proved inadequate to reach priority minority groups.
This awakening must have a long-lasting legacy in order for biopharma to rebuild public trust. One silver lining of the pandemic is the acceleration of tools and capabilities that enable study sponsors and investigators to recruit diverse populations. Trial designs that lower the burden on participants will also improve overall diversity, a key benefit of the wider trend towards decentralization of clinical research. These advances mean that there is not a direct cost associated with focusing on diversity, but rather the potential to build a virtuous circle whereby smarter trials produce representative clinical data, resulting in engaged participants and investigators.
Biopharma must also lead this change and not wait for regulatory enforcement to catch up. It is uniquely placed to do so, influencing its peers and the ecosystem around it. Diversity can become a requirement for due diligence when selecting contract research organizations and biotechs with which to partner.
In 2020, just as the pandemic was beginning to surge and national lockdowns were enacted, Pharma Intelligence published its annual snapshot of the industry pipeline. () The general picture was one of rude health, with impressive 10% annual growth outstripping the rates of prior years. This expansion however was not shared equitably, as the unrelenting focus on oncology came at the expense of other therapy areas. The collective oncology pipeline grew 14%, now accounting for a dominant 37% of all development assets. Conversely, the number of infectious disease programs has stagnated against this backdrop of wider growth. As Exhibit 3 shows, this remodeling of the pipeline has been slow and inexorable, as investors and drug developers prioritize commercial returns over a holistic view of unmet need.
When one area dominates so much, as oncology does in the pharmaceutical industry, there is always a trade-off and a price to pay. Historical underinvestment in infectious disease and pandemic preparedness left governments and vaccine manufacturers in a poor starting position. It is perhaps unsurprising that several of the incumbent big vaccine players – GlaxoSmithKline, Merck, and Sanofi, have collectively struggled to meet the demands of a pandemic threat. Their cash cow vaccine businesses have faced relatively little threat, protected by high competitive barriers and unattractive returns, reducing the need to innovate to stay ahead. We therefore owe a huge debt of gratitude to biotech and academic groups, whose novel vaccine platform development has bailed out the wider vaccine effort. This has coincided with extremely buoyant capital markets, providing the fundraising environment that will catapult innovators in mRNA, viral vector and protein subunit vaccines into standalone and sustainable commercial entities. These companies are now protected by sky-high market capitalizations, which in turn will breathe fresh life into the stagnant vaccines sector.
Years of investment into disease-agnostic platform technologies have been richly rewarded, and this is a lesson that must be heeded in the long-term. The industry cannot continue to prioritize oncology above all else, and a wider rebalancing towards unmet need is sorely needed. It might be naively assumed that the pandemic has jolted the pipeline into a new order, although a preliminary look at the numbers for Pharma Intelligence’s upcoming 2021 pipeline review shows that peak oncology has not yet been reached – the share has grown again to 37.5%.
While pharma certainly needs to pay close attention to its portfolio balance and be mindful of the collective unmet need across all of human disease, help from regulators, governments, and markets is also needed. Sustainable development requires incentives, and the dominance of oncology is simply a reflection of where the return on investment is highest. For a new, healthier research agenda to follow, pharma must be allowed to profit in new disease areas. COVID-19 is certainly an immediate opportunity – Pfizer estimates sales of $15bn for its vaccine this year – and a positive legacy of this profit resulting in new successes in other infectious diseases will be important. This will help bring the public on board and protect the future of our industry, as its emphasis moves away from treating illness and toward promoting health and wellbeing.
This article is based on a series of presentations prepared by Daniel Chancellor, thought leadership director, Pharma Intelligence and Duncan Emerton, custom intelligence director, Informa Pharma Consulting in February 2021. It also complements a prior analysis of COVID-19’s negative effect – or scarring – of biopharma R&D, available here. If you have any questions about any of the themes discussed in this article, or would like to learn more about Pharma Intelligence’s products and consulting offerings, please contact Daniel or Duncan.
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