Among the five permanent United Nations countries, the one that invented the vaccine is the only country not to have found one against Covid-19, notes professor Frédéric Bizard, the President of the Institut Santé (Health Institute), in an op-ed published in Le Monde. France’s ally and competitor in the European Union, Germany, will have developed two with the winning messenger RNA technology before the end of the first half of 2021.

A sign of an irreversible decline in French medical research for some, an accident linked to any research process for others, this disappointment should be analysed without demagoguery and must lead to action without further delay. The process of medical innovation is typical of the complex thought dear to Edgard Morin, which requires distinguishing the elements that make it up and linking them in order to understand their interactions. Let’s draw up a diagnosis and an action plan to relaunch medical innovation in France.

Three loopholes and a mess

The first flaw lies in fundamental research, therefore at the genesis of the innovation process. While France already has a lower overall public research budget than our European neighbours (2% of GDP vs 3% in Germany), the country has made the surprising choice to reduce the share of this budget dedicated to the sector of health. From 2011 to 2018, loans fell by 28% to $ 2.5 billion while they increased by 11% in Germany to more than $ 6 billion over the same period.

France thus shot itself in the foot, condemning its research to decline. This is a strategic error in a period of technological paradigm shift with the transition that has been taking place for more than 20 years from chemistry to biology and genomics. One in two innovative drugs today comes from biotechnologists. It is basic research that generates the first discoveries from which the process of innovation leads to a drug or a vaccine. It therefore conditions this process and its chances of success.

The second flaw is organizational. The creation of the National Research Agency in 2005 did not create the expected impetus to boost innovation, not simply because of a lack of resources but because of an overly bureaucratic operation and a poorly thought out link with existing institutions (Inserm, Cnrs). Insufficient cooperation between universities and businesses is also a French weakness. In 2017, France was ranked 35th in the world in the World Bank ranking for this collaboration (Germany was 7th, the USA 4th) which is decisive for the successful transformation of fundamental research into applied research, and therefore that of discoveries into products.

This organizational flaw undermines France's attractiveness to the best researchers. If France has not succeeded in bringing 2020 Nobel Prize winner Emmanuelle Charpentier back to her country despite numerous attempts, it is for financial reasons but also for the bureaucratic organization of our research ecosystem. The stars of global research need to be attracted with a specific financial package, and to be able to organize their teams around them. Research is driven by a few brains that you have to know how to attract, otherwise innovation takes place elsewhere.

In addition, as biotechnology and genomics skills are insufficient in big pharmas, the key to the success of applied pharmaceutical research now lies in biotech companies, which are small in size and whose ability to finance themselves is a major issue. We are touching the third flaw in our ecosystem. 72% of biotechs were looking for funds in 2019 in France, but the venture capital market is too underdeveloped there. The biopharmaceutical sector is indeed characterized by a very high initial capital requirement, for a long development period (more than 10 years) and a high risk of failure (more than 95%). Thus 82% of the capital of biotechs comes from national funds in the USA, against 11% in France. Without these funds, there is no salvation for biotechs!

These flaws are a real waste, as France has been a pioneer in genomics and retains world-renowned researchers in this sector. From 1965 Nobel Prize winner Jacques Monod, discoverer of messenger RNA to Emmanuelle Charpentier, via 1980 laureate Jean Dausset, France has the three Nobel Prizes who have shaped genomic research. The talent of our researchers, the rarest and longest research resource, is an essential factor of hope for rebounding.

An industry plagued by an archaic ecosystem

The industry has been facing a radical change in business models since the 2000s. The former model (known as the blockbuster) has developed since the 1980s through the standardized mass production of innovative chemically-based drugs protected by worldwide patents that ensured funding for internal research and high profits. The new model (called custombuster) is characterized by the use of biological and genetic processes and the customization of the use aimed at targeting the most responsive patients. This development has been accompanied by a very sharp increase in drug R&D costs. From 2003 to 2016, the average drug development cost tripled (from $ 800 million to $ 2,558 million).

In spite of this situation, there has been a slowdown in the growth of R&D investments in France over the last ten years. The share of turnover invested by pharmaceutical firms in R&D in France decreased from 12.5% in 2008 to 9.8% in 2017. French leader Sanofi moved from 4th place in 2007 in investments in R&D, to tenth place in 2020

In addition to research, France's dropout is also very marked in pharmaceutical production. After having been the European leader from 1995 to 2008, France is now behind Germany, Italy and Switzerland. The most damaging thing is that the French production tool is 80% dedicated to chemical drugs, which are very largely outsourced to low-cost producing countries, such as China and India. This positioning is incompatible with structurally high production costs in France, which requires positioning on the high end, the production of biotech and genomics.

The regulatory ecosystem for health products is ineffective with the intervention of several agencies (ANSM, HAS, CEPS) whose missions are entangled, and the use of archaic evaluation criteria. The time to market access is 566 days in France vs. 127 days in Germany, which illustrates the ineffectiveness of the system. If we add that the French market has lost its attractiveness due to lower prices (-9% vs Germany), high taxes (10.7% of turnover) and zero net growth since 2009, we better understand the decline of our national pharmaceutical industry.

Finally, the pharmaceutical industry has been the victim of an economic policy for thirty years which has led to greater deindustrialisation in France than in other developed countries, with a drop in the share of GDP from 24% in 1980 to 12,5% in 2018, and a loss of 2.5 million jobs in industry.

An Airbus and a systemic overhaul

A way out of this situation of failure exists for the French industry, and the health crisis can serve as a leverage effect. First, the country of Pasteur and Monod can legitimately create an Airbus of messenger RNA which would bring together a consortium of public and private actors dedicated to the research and production of innovative products based on messenger RNA (an initiative proposed to the French state by the Institut Santé). The development and massive production of multivalent messenger RNA-based vaccines will probably prove necessary to put an end to the pandemic, and require pooling several resources and expertise that are scattered today. This messenger RNA-based technology park, a technology of the future for many treatments, will be the biotech flagship that France lacks. It is also intended to accommodate French biotech companies working on other innovative health technologies.

Second, systemic reform is needed in health products research, governance and financing. Doubling the annual public funding of basic research and improving university-business collaboration are essential. Funding through calls for fundamental research projects should be upgraded to give greater autonomy and to be more attractive to the most efficient researchers. National funds must further finance the capital of promising biotechs. The various existing regulatory agencies are to be brought together into a single innovation agency, endowed with the skills necessary to regulate the new pharmaceutical business model. A 5-year health planning law is to be introduced to give stakeholders a long-term vision.

This knife blow received in our national pride should make us realize the gravity of the situation, but also our ability to bounce back. The latter requires acting quickly and applying the measures proposed above, which are within France’s reach if the political will is strong. The stakes are high for the future of the country!

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