CureVac Story of a disappointed hope

Status: 06/17/2021 8:30 p.m.

While the world is now being vaccinated with BioNTech, the vaccine from CureVac has proven to be ineffective. How could the two great German hopefuls develop so differently?

By Thomas Aders and Sebastian Deliga, SWR

At first it was a German head-to-head race between the Mainz-based pharmaceutical company BioNTech and the Tübingen researchers from CureVac. Both use the same technology “Messenger RNA”, the share prices of both companies initially took off on the stock exchanges, and both have professional and global partners. The Mainz-based company was able to bring the US pharmaceutical giant Pfizer on board, while the Tübingen-based company found what they were looking for at Bayer. And not only that: At the beginning of September, a man came to visit Tübingen, whose name makes technology enthusiasts, e-mobility enthusiasts and stock market speculators enthusiastic: Tesla boss Elon Musk. Even before he paid his respects to Chancellor Angela Merkel in Berlin, he stopped by CureVac. For the production of their vaccines, the people of Tübingen used the technology of the medium-sized company Grohmann in the Eifel, which in turn has been part of the Tesla empire since 2017.

The field of support from both companies was also in competition: in Tübingen, SAP boss Dietmar Hopp became the majority owner, in Mainz the twins Thomas and Andreas Strüngmann, who had become rich in the pharmaceutical business, and the Bill & Melinda Gates Foundation were behind BioNTech boss Ugur Sahin. From the outside, it was still the duel between digitization pioneer Hopp and oncology professor Sahin. Both were believed to be successful.

But since the beginning of 2021, the people of Baden-Württemberg have stumbled in the race against the Rhineland-Palatinate; while the BioNTech drug was approved by the authorities, CureVac has still not fully completed the third phase of its vaccine testing. Today’s publication of the inferior efficacy of the Tübingen vaccine candidate CVnCOV of only 47 percent – in contrast to 90 percent for BioNTech / Pfizer – was the end of hopes for mass production soon and the end of hopes for strong profits on the stock market; the price of CureVac has more than halved.

Why does the vaccine protect so poorly against Covid-19?

When the Tübingen-based company delayed the crucial phase 3 and tested the vaccine, there were already several mutations of the corona virus. That made research much more difficult. Virologist Martin Stürmer from the University of Frankfurt also sees this as one of the problems: “BioNTech, AstraZeneca and Co. – they only had to deal with B.1.1.7 (the Alpha variant, first developed in England).” In addition, it was the Tübingen’s unwritten law to administer RNA as pure as possible and not chemically treated. This also had fatal consequences for CureVac, because the competition achieved a much higher concentration by modifying the messenger RNA. The head of the CureVac vaccination study, Peter Kremsner: “BioNTech and Moderna were able to dose three to ten times as high because they chemically changed the RNA. At CureVac, the dogma was that the RNA should be injected as unchanged as possible, which is basically correct, but unfortunately it did not work.” The goal of the Tübingen was a noble one. And the SPD politician and epidemiologist Karl Lauterbach is talking about the company’s fate today tagesschau.de “terribly sorry”. He always admired the particularly ethical and moral standards of the Tübingen population. But Lauterbach no longer sees any basis for hope either. Even if CureVac starts all over again, the competitors from BioNTech or Johnson & Johnson, for example, have made further progress in their research. So the Tübingen train left for many.

What does this mean for the vaccination campaign in Germany and Europe?

Epidemiologist Lauterbach very much regrets the bitter fate of CureVac, but he sees the German vaccination campaign as hardly endangered in the Tübingen disaster. Several other vaccines worked to a great extent in his opinion, and in his view today’s setback would result in a delay of no more than three weeks. “By the end of September we will probably have a vaccination rate of 70 percent, and thus herd immunity.” The Federal Ministry of Health is also anything but panicked. Got the latest news about CureVac “no impact on the pace of our vaccination campaign”. Brussels does not want to comment directly on the CureVac disaster, that is a matter for the European Medicines Agency (EMA) in Amsterdam, which decides on the approval of vaccine preparations. However, the EU has apparently taken precautions in the event that CureVac fails: The contract with the Tübingen region includes “Termination clauses in the event that the vaccine is not approved by the EMA”. There are also rather composed comments from Parliament: of course, the results at CureVac are inadequate “a big disappointment”, said MEP Peter Liese. “The goal of offering people in Germany and Europe a vaccination offer by the end of the summer is still realistic.” This is due to the positive developments at BioNTech and Johnson & Johnson. Additional information is interesting in Peter Liese’s statement: CureVac CEO Franz-Werner Haas had already promised him in December that his company would work with other manufacturers, “if your vaccine doesn’t work”. With today’s publication of this conversation note, the pressure on the Tübingen-based company and its partner Bayer should now have increased rapidly to cooperate quickly with successful competitors from Mainz and to convert their own capacities to the production of BioNTech.

Did the state lose money promoting CureVac?

“The federal government is participating in this promising company because it expects it to accelerate developments and to enable CureVac financially to exploit the potential of its technology.” Federal Minister of Economics Peter Altmaier said that almost exactly a year ago. The federal government then invested 300 million euros in the Tübingen-based company. In addition, there was the Federal Ministry of Research, which made a commitment for funding of 251.6 million euros.

All in all, a good half a billion euros. So is the money gone now? The answer: only in part. On the one hand, the federal government received a share in the company for its investment. And although CureVac’s price has slumped by more than half today, the value of that portion is still likely to be significantly higher than when the company went public. And on the other hand, of the promised 251.6 million, only 102.8 million euros have actually flowed so far, as the Ministry of Research tagesschau.de confirmed today. The rest will probably be withheld as the payout “depending on the progress of the project” is. Regardless of the possible “Losses” The question arises, however, what would have happened if the federal government had not invested a cent in promising companies such as CureVac or BioNTech. An outcry would probably have gone through the republic, even though an alleged takeover offer by ex-US President Donald Trump turned out to be a hoax. The situation in the crisis year 2020 was dramatic, according to SPD health expert Lauterbach. “It was an extremely noble attempt by our German companies to develop a new type of Covid vaccine and make it available to the whole world. The investments were right, although in the case of CureVac there was no success.”

CureVac vaccine not very effective Crash of a Bearer of hope

Status: 06/17/2021 12:31 p.m.

CureVac’s vaccine proves far less effective than hoped, with the biotech company’s stock plummeting. What does this mean for the vaccination campaign and German taxpayers?

From Angela Göpfert, tagesschau.de

For the company CureVac and its owners, dramatic scenes have taken place in the past few hours. The price of the Tübingen-based company listed on the US technology exchange Nasdaq had already halved in after-hours trading on the US stock exchange on Wednesday. This morning, the CureVac share then rushed in German retail by up to 52.4 percent.

Eight billion euros destroyed on the stock exchange

This destroyed around eight billion euros in market value within a few minutes. This melted down from over 15 to a good seven billion euros. The drastic course reaction shows how surprisingly, despite all previous doubts, such devastating study data as CureVac has now presented, came in the end – and how serious the consequences could be.

On Wednesday night, CureVac announced that its first-generation vaccine candidate was CVnCoV only an effectiveness of 47 percent against a Covid 19 disease of any severity. The company thus missed the intended statistical success criteria for approval.

Completely out of the vaccination campaign?

The study is to be continued, and the degree of effectiveness could change with higher case numbers. However, if the current trend continues, approval is unlikely. In this case, experts say CVnCoV would be a total flop for the company. For the German vaccination campaign, CureVac is therefore canceled until further notice. “According to these study results, it will be extremely difficult for CureVac to play a role at all in the current vaccination campaign”, told LBBW analyst Timo Kürschner tagesschau.de . According to the federal government, the setback for the Tübingen company does not upset the vaccinations in Germany. “This announcement has no effect on the speed of our vaccination campaign”said a spokesman for the federal health ministry.

Other manufacturers are still catching up

Industry observers believe that speed is just as important in vaccine development as it is in drug development. “Late bloomers like CureVac only have a chance if they have a better effect profile or fewer side effects”, explains pharmaceutical expert Kürschner.

“The more time that elapses, the more efficient the production of vaccines that have already been approved will be”says the pharmaceutical expert. “BioNTech & Co. are then more and more able to serve the required delivery quantities.” His conclusion: “We could get to a point where you actually no longer need the CureVac vaccine because the vaccination campaign is already so advanced.”

Hundreds of millions from the federal government

The severe setback for CureVac meanwhile has effects beyond the current vaccination campaign. It meets the German taxpayers – after all, the federal government has a stake of around 16 percent in the company and has supported vaccine development with a special program worth several hundred million euros. It is also a debacle for SAP co-founder Dietmar Hopp, who holds almost 50 percent of the shares.

Last but not least, the CureVac price disaster hits the countless private investors who have invested their money in the share. The paper of the company, which is legally based in the Netherlands, has been one of the most traded foreign stocks in the past few weeks on the Stuttgart Stock Exchange, where many private investors cavort.

Recently increased warning signs

Recently, there had been more and more indications that the CureVac vaccine could fail for the time being. Even when Health Minister Jens Spahn, according to media reports, deleted CureVac from the federal government’s planning for the current vaccination campaign, this could hardly affect the share.

The high market capitalization compared to rival companies was also a warning sign: Before the current price crash, CureVac had a higher market value than Novavax. The US manufacturer had already reported a Phase III study on Monday, according to which its vaccine had a has a high effectiveness of 90 percent .

Often high risk in the industry

For CureVac and its owners this is now the “Worst case” of a biotech company. At the same time, the CureVac case also shows the general risks facing the industry. Companies in this industry usually have very few active ingredients in their pipeline. If one then fails – for whatever reason – it often has fatal consequences for the entire company.

LBBW expert Kürschner also sees CureVac “a prime example of the risks involved in investing in biotech companies”. However, Kürschner does not fear negative consequences of the CureVac events for the German biotech industry. After all, there is a positive counterexample in the country. “I’m sure: BioNTech’s success story will outshine the rather negative course at CureVac.”

From Angela Göpfert, tagesschau.de No question about it: digital photography has many advantages. There is no longer any need to buy, change or develop films, and the result can be viewed immediately. And yet there are quite a few photo lovers who miss the charm of analog photography. Both amateurs and professionals then and now really only had the choice between Fujifilm or Kodak. While Eastman Kodak had to file for bankruptcy in 2012, Fujifilm, which was founded in Tokyo in 1934, was able to assert itself in the market – not least thanks to various other pillars, for example in medical technology and pharmaceutical research.

Fujifilm has long since ceased to manufacture only film rolls. One of the pharmaceutical products from Fujifilm has been causing new bursts of hope, but also disappointment, at least since the outbreak of the corona pandemic: Avigan. A Fujifilm subsidiary originally developed the drug as a flu drug.

Shortened illness time

The new Phase III study, launched today, is to review the effectiveness of Avigan in treating Covid 19 patients who are over 50 years old or who are at high risk of a severe course. This is a so-called double-blind study; so neither the investigator nor the patient know whether the drug or a placebo is being administered in a specific case. Fujifilm had already presented the results of a phase III clinical study with 156 Covid-19 patients on Avigan in autumn 2020. Accordingly, the duration of treatment when using Avigan was reduced by three days.

Virus replication is blocked

But how does Avigan actually work? The active ingredient, favipiravir, inhibits the viral “copying machine”, the so-called RNA polymerase. This blocks virus replication. At first glance, it is similar to Remdesivir – the first corona drug that was approved in Germany. However, according to new studies, remdesivir cannot completely stop viral reproduction. Avigan has demonstrated effectiveness against a wide range of viral pathogens, including many types and subtypes of influenza viruses. In 2014 it was successfully used against Ebola. In 2016, the Japanese government delivered the funds to Guinea as emergency aid to fight the Ebola epidemic. Medical professionals assume that the drug can also inhibit coronavirus RNA polymerase. After all, like influenza viruses, these belong to the RNA viruses.

In most countries only reserve drug

Today, Avigan is already approved as a Covid-19 treatment in some countries such as Russia, India, and Indonesia. In many other countries, it is only used as an emergency drug for sick people for whom there is no other treatment option. In Germany, according to the Federal Institute for Drugs and Medical Devices, it can be used as part of an individual healing attempt. By the way: Even when it was originally used as a flu remedy, Avigan has not yet been able to meet the high expectations. Hopes that Avigan could even replace the well-known flu drug Tamiflu should not come true. This is not least due to the serious side effects of the drug. Avigan has been shown to be “teratogenic” in animal experiments: It led to fetal malformations and could even be detected in sperm. Avigan is therefore only used as a reserve drug against influenza in his home country Japan, so it is only used when alternative drugs fail.