The Great Coronavirus Collaboration And The Future Of Drug Discovery – Forbes

The Great Covid R&D Collaboration - Cooperation accelerating drug development

Pharma battles coronavirus with a mega-collaboration; its own health requires competitive balance.

Pharmas search for a vaccine or drug to prevent/treat Covid-19 has fostered collaboration among companies on an unprecedented scale.The new business model brings together the best minds in the industry to compress into months the search for a drug or vaccine and subsequent clinical testing that typically take decades.While there is no guaranty that any of the candidates chosen will achieve a timely cure, the scale of the effort has led even conservative experts like Dr. Anthony Fauci to predict that a vaccine could be available as soon as yearend, compared to the current world record of six years for the Ebola vaccine.

The worlds expectations pose a serious challenge for pharma.Industry observers, like Bernard Munos and Jack Scannell, have documented a decades long decline in productivity.One might reasonably ask, if collaboration is able achieve these results in a crisis, could it do the same against the major diseases, like cancer and Alzheimers disease, which together kill more each year than Covid-19?Could a cooperative industry be more productive than a competitive one?

The Power of Collaboration

In the last eight months the pandemic has emerged with stunning suddenness to infect more than 6.5 million people world-widekilling nearly 400,000.Cambridge University estimated that losses over the next five years would total nearly $27 trillion, more than 5% of global GDP.As the world hopes for salvation, how pharma responds will have a profound effect on its future.

Though related to predecessors like SARS and Ebola, the CoV2 virus has a unique structure and genetic signature that will likely require new medicines from an industry with an unimpressive track record at innovation.The era of modern molecular medicine began only 40 years ago and is still in relative infancy.Over the last five years, pharma have brought to market an average of 44 new drugs, costing over $2.5 billion each and many taking more than a decade.Pharma will need all their collective wisdom and resources to stop this viral firestorm before it runs is course.

In response, industry leaders have created a mega-collaboration within the commercial research community.Safi Bahcall, writing in the Wall Street Journal, explained that nearly all the major players in drug discovery and development have[established an] insider-only collaborationcalled Covid R&Dto accelerate creation of a vaccine or cure.In these unprecedented discussions, sworn competitors have shared proprietary data from promising drug candidates that they ordinarily would guard like prized jewels.Representatives of the Food and Drug Administration have even joinedto offer assistance.

With businessmen and attorneys out of the room, scientists across the industry can identify and advance projects at rates far faster than any single group. We dont need four companies with four versions of the same drug running redundant clinical trials at the nations hospitals, yet thats what we have today. In normal times, thats how business is done. But these arent normal times. Either industry leaders should empower their consortium to decide which companies should sacrifice their redundant programs, or the federal government should step in and do it for them.

Tahir Amin, Co-Executive Director of Initiative for Medicines, Access & Knowledge and Rohit Malpani, former policy director for Medecins Sans Frontieres, writing in STAT, claim that pharma could be better prepared for pandemics and more responsive to global health-care needs, if existing research [took] place in a more open and transparent manner, even if it is protected by intellectual property. The pharmaceutical industry sits on libraries of patented molecules and research, some of which originates [sic] from public funding, but which is [sic] not developed unless market opportunities arise.[In the case of remdesivir a] more transparent and open science platform could have motivated broader research participation earlier and potentially saved valuable time andimproved collective understandingof the drug.

The Problem With Collaboration

The Covid R&D collaboration focuses, not on drug discovery per sethere is no time for thatbut on selecting or modifying the best of candidates already on the market or in development and accelerating their path to the bedside.This is engineering on a grand scale.But can it help with invention, which is needed to sustain the industry in normal times? Are the competitive friction and apparent inefficiency of business-as-usual impediments to progress or essential elements in a productive commercial ecosystem?

While required in a crisis, cooperation fails as a sustainable foundation for the pharmaceutical industry, because it dilutes incentive and does not support the quantity and diversity of research required for a strong, responsive industry.Innovation does best with many competing high-risk, high-reward projects, rather than a single coordinated effort.Competitive costs are more than covered by the value of the breadth and flexibility of the industry that a collaboration eliminates in the interests of speed.

Drug development is experimental innovation, based on trial-and-error.In a world where nine-candidates-out-of-ten fail in clinical trials and only one-in-five approved drugs is a commercial success, researchers do not know what will work against CoV2 or any pathogen.When outcomes cannot be predicted in advance, likelihood of success is proportional to the number of candidates tested and the degree to which they are differentiated from one another.

In the collaboration, senior team members set an agenda based on their expert judgment, narrowing the range of research to accelerate the development of a few of the most promising candidates.In the case of Covid-19, it means picking winners without clinical or market data, i.e. guessing.

With Covid the strategy has a good chance of yielding results, because the technology for targeting viruses is relatively advanced; the target is well characterized and, according to Michael Farzan at The Scripps Research Institute, more druggable than most targets; the timeframe is short; the scope is enormous, encompassing many candidates; and the cost of failure or delay is so high that it justifies massive spending, regardless of risk.

The problem for innovation is not in streamlining but making decisions based on expert opinion.A 2013 article in Nature Reviews Drug Discovery showed that the single factor that correlated most closely with success in drug development was managements willingness to kill candidates early, based on data.The Covid R&D alliance has no choice but to rely on judgment, given the timeframe.In contrast, normal drug development is true scientific research.Knowledge evolves through the Darwinian selection of candidates, based on experimental outcomes.Failures play at least as important a role as successes in guiding development.Second-tier performers may find uses in other indications.Knowing only what works gives developers no indication of where to go next when they encounter a block.An unexpected toxicity can eliminate an entire generation of drugs with a similar mechanism.

Expert opinion is not a substitute for the time and cost of competitive studies.Rather than choosing winners, researchers should aggressively cut weak performers early in development.By testing more drugs, more quickly with greater diversity, developers can improve productivity.

Though the scale of the collaboration can reduce the risk somewhat with more shots-on-goal, the lack of time diversification limits the technological base to the ideas and molecules available at the moment, excluding newer, untested and often unorthodox approaches.Should the current solutions prove inadequate, the collaboration would essentially have to start over.

If It Looks Like Collaboration

The threat of consensus thinking doesnt require the formal structure of a collaboration.The infatuation of the industry with the amyloid hypothesis of Alzheimers disease caused a similar narrowing of the industry focus to a single idea.Pharma has spent well over a decade and billions on the assumption that amyloid plaques and tangles caused the disease but have no approved products or even positive clinical results to show for the effort.Rather than assuming that the experts knew the answer, despite having no data proving causation, the industry would have been better served by testing as many different hypotheses as possible.With the presumed mechanism a bust, the industry have few promising alternatives and are essentially back where they were 10 or more years ago.

Contrary to Amin and Malpani, forcing access to proprietary molecules and data would not accelerate a treatment for Covid and would compound the collaboration problem longer term.Without the results of the phase II trials, it is unlikely that, out of hundreds of potential projects, investigators would have chosen in advance to work on remdesivir, a drug that had failed in HCV and Ebola and may offer only limited protection against Covid 19.Making available proprietary data that Gilead had spent tens of millions to acquire, along with the rights to the molecule, would destroy any incentive to invest in early stage research.

The commercial innovation machinery with all its redundancy and friction has provided a remarkably quick initial responselittle more than 8 weeks after the declaration of the pandemic, the FDA issued an emergency use authorization for remdesivirand set the stage for a more complete solution in the coming months.With ninety vaccines of eight different varieties in clinical trials as reported by Nature at the end of May and more on the way, competitive excess has enabled the industry to mount a robust response to Covid threat.One hopes it will be enough.

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The Great Coronavirus Collaboration And The Future Of Drug Discovery - Forbes