The first domestic new crown "special drug" has come, but the pricing has become a problem

Text/Shi Hanxu

A new variant, Omiljung, which has appeared in 77 countries and territories and is "spreading at a speed we have not seen in any of the previous variants" (in the words of WHO Director-General Tedros Adhanom Ghebreyesus), is still coming.

On these two days, Tianjin and Guangzhou successively reported that they were infected with the Aomi Kerong variant strain imported from abroad.

The good news is that the first domestic COVID-19 "special drug" has just passed the emergency approval of the State Food and Drug Administration, and clinical data shows that it can reduce the risk of hospitalization and death of patients by 80%. A few days ago, one of its research and development parties, Tengsheng Bo Pharmaceutical, announced that the neutralization data in vitro trials showed that the new crown neutralizing antibody combination therapy maintained the neutralizing activity of Omicron.

Domestic vaccine companies Zhifei Bio and Kexing have also announced that they have completed three injections of vaccination, which still has the ability to neutralize Aomi Kerong.

At this point, the "seedling + medicine" is both in hand, and the current tense form of epidemic prevention seems to be alleviated.

It is quite interesting that the price of this first approved "special drug" does not seem to be too cheap. Previously, some media reported that the price of the combination therapy was 8,000 yuan / person.

However, Tengsheng Bo Pharmaceutical did not recognize the pricing at the press conference. Luo Yongqing, president and general manager of greater China, said that "discussions have been held on the government's strategic reserves and procurement, and they are still in progress."

"At present, it is basically a national procurement possibility, however, from the research and development, preparation, production costs of neutral antibodies, and the number of confirmed cases retained and newly added in China today, the pricing of the therapy is ultimately unknown," industry insiders revealed. At the same time, how to purchase, or the proportion of self-payment after entering the medical insurance catalog, etc., still needs to wait for the government's calculation results.

The industry insider speculated that after the government intervened, the price of 8,000 yuan may drop by 70%. "It may not even be more," the head of pricing and market access at a biopharmaceutical company told China Newsweek.

There is finally a "special drug" in China

At present, the proportion of the population covered by the full covid-19 vaccine in China has reached 82.5%. However, in recent rounds of the epidemic, the continuous emergence of breakthrough cases (that is, those who have been diagnosed with infection after completing vaccination) and the appearance of new variants have made people expect a new coronavirus special drug to appear.

Internationally, Merck's oral COVID-19 drug Molnupiravir has been approved for marketing in the UK, and Pfizer's Paxlovid's recently updated clinical final analysis data shows that the drug can reduce the risk of hospitalization or death by nearly 90%.

Domestic pharmaceutical companies have also developed new crown drugs through a variety of technical routes, and have entered the clinic. Under the expectation of all, China's first independent intellectual property rights of the new crown drug finally passed the emergency approval of the State Food and Drug Administration last week, suitable for the treatment of adults and adolescents mild and ordinary type, accompanied by the progression of severe high-risk factors of the new crown virus infection.

Specifically, the "special drug" is composed of two neutralizing antibodies - amphavir monoclonal antibody and romimavir monoclonal antibody - which are isolated and screened from the serum of patients who have recovered from new crown pneumonia.

According to Luo Yongqing, the two antibodies of the combination therapy bind different epitopes of RBD in the binding region of the new coronavirus spike glycoprotein receptor, in addition to preventing the new crown virus S protein from binding to the human ACE2 receptor, it can also prevent the cell membrane fusion after the collection of the two, thereby blocking the virus from entering human cells to a greater extent.

The clinical phase III results of this neutralizing antibody combination therapy are more impressive. After a randomized, double-blind controlled trial of 847 mild to moderate patients at risk of progressing to severe (hospitalization or death) WITH COVID-19 in six countries around the world, the results showed that the therapy reduced the risk of hospitalization and death by 80%, with no deaths in the medication group compared to nine deaths in the placebo group.

You know, a newly released clinical data from Merck shows that monupipipvir only reduces the risk of hospitalization and death by 30%.

Since the outbreak of the epidemic in Shenzhen in May this year, Tengsheng Bo Pharmaceutical has donated drugs to Guangzhou, Ruili, Nanjing, Yangzhou and other regions, with nearly 900 cases of clinical treatment. "Clinicians have responded positively, and after taking the drug, the patient's symptoms are alleviated, the virus declines, and immune indicators rise," Luo Yongqing said.

More impressively, the half-life of the therapy can be from 76 days to about two or three months, which means that its effective concentration in the blood is maintained for a long time. This means that the protection provided to the human body will be more long-lasting.

A few days ago, Tengsheng Bo Pharmaceutical issued an announcement that the new in vitro chimeric virus test showed that the combination therapy maintained the neutralization activity of Omi kerong.

Pricing dilemmas

However, there have been previous reports that the price of the combination therapy is 8,000 yuan / person, which has caused the public to express concerns about its accessibility.

Although Li Ankang, chief financial officer of Tengsheng Bo Pharmaceutical, said that the pricing is "not yet determined, and it is still communicating with the government." Factors such as pricing and government procurement are related", but the price is not cheap and not surprising.

If the United States is used as a reference, the government-procured regeneration yuan new crown neutralizing antibody combination therapy, the average price of each dose reached 2100 US dollars, which is more than 13000 yuan.

It should be known that the cost of clinical phase III trials alone may be as high as hundreds of millions of yuan in the removal of investment in early research and development. In September this year, Tengsheng Bo Pharmaceutical also announced an additional US$100 million to promote the global registration application and commercialization process of the combination therapy, which shows the large investment in research and development.

At the same time, the process of antibody drugs from cell culture, purification to preparation is more complex, and the production cost is also very high.

According to relevant people, WuXi Biologics, which produces drugs for Tengshengbo Pharmaceuticals, has a production cost of less than 80 US dollars per gram of antibody drugs under the scale of 12,000 liters, and "the larger the production scale, the lower the price". The combination therapy of Tengsheng Bo Medicine is to inject one dose of 1 g of amphavenumab + 1 g of romizumab per person, and ideally the production cost will exceed 1000 yuan.

"The cost-scale benefits of biopharmaceuticals are significant," the head of price and market access told China Newsweek. In the epidemic prevention stage of China's dynamic clearance, even if the current round of epidemics from Manchuria and then the recent epidemic in Zhejiang have fluctuated, the patient base is still very small, and the domestic demand for neutralizing antibody drugs is probably very limited, which will make it difficult to further reduce costs and the market size is very limited.

Considering the particularity of being a new crown treatment drug, the possibility of national procurement is extremely large, but the industry insiders believe that the purchase volume will not be too large. The extent to which prices can be reduced is still unknown.

Combined with the price of the previous PD-1 medical insurance negotiations, some insiders believe that the purchase price of Tengsheng Bo's combination therapy may also fall by more than 70%.

The person in charge of price and market access believes that the price reduction may be even greater. In his view, the national procurement should do pharmacoeconomic testing to see how much benefit the drug brings, how much it can shorten the course of the disease, and how much to save the original treatment cost of new crown patients.

"At present, from a clinical point of view, neutralizing antibodies are not revolutionary therapies and cannot replace all previous treatments," the person in charge said.

Because of this, for patients, it is not clear at what price and in what way the drug will eventually be used.

For enterprises, lower prices, limited markets, their financial pressure is obviously very large. But such a dilemma is not completely out of the way.

AstraZeneca's long-acting COVID-19 neutralizing antibodies, which are authorized for emergency use by the U.S. Food and Drug Administration (FDA), are approved for pre-exposure prophylaxis in specific adults and adolescents. "Although they are all neutralizing antibodies, the application of treatment and prevention varies greatly in terms of market size, and in China it may even be a gap of hundreds of people and tens of millions of people," the person in charge said.

In fact, Tengsheng Bo Pharmaceutical revealed that the company is also exploring clinical evidence in terms of prevention indications to meet the needs of prevention and protection of people with urgent prevention needs, immunodeficiency or poor response to vaccines.

This is also an advantage of neutralizing antibodies over small molecule oral drugs, "it is unlikely that a healthy person can take small molecule drugs for a long time as a prevention, but a long-acting antibody injection can protect at least 6 to 9 months, and the potential in prevention is great," Li Ankang said.

In addition, according to Li Ankang, Tengshengbo Drug's new crown neutralization antibody combination therapy has submitted an emergency use authorization application to the US FDA in October, and it is expected to be approved in the near future. Once approved, its pricing in the United States will be benchmarked at the current $2100 per person, and international sales may alleviate its significant cash flow pressure.

Of course, in the current situation that there are 3 neutralizing antibodies or combination therapies in the United States that have obtained emergency use authorizations, how the latecomers will cut a piece of cake is another story.