New crown prevention and control trilogy (part 2) - Inventory of global new crown oral drug research and development progress

The new coronavirus that continues to mutate and evolve has become increasingly contagious, posing a serious threat to human life and health, and the strict quarantine and control policies have intensified the downward pressure on the econo.

At this moment, the "special drug for the new crown" has become the focus of attenti.

New crown drug development ideas

New crown drug development ideas

The new coronavirus is a single-stranded positive-stranded RNA vir.

At present, new crown drugs mainly focus on the three targets of spike (S) protein , 3CL protease , and RNA polymerase

Spike (S) protein 3 CL protease RNA polymerase

Neutralizing antibodies bind to the receptor binding domain of the spike (S) protein on the surface of the new coronavirus, thereby blocking the binding of the virus to ACE2, preventing the virus from entering cells, and playing a therapeutic effe.

The development of neutralizing antibodies is fast and can be approved for marketing first, but it is easy to weaken or lose efficacy due to immune escape caused by the mutation of the S protein on the surface of the new coronavir.

FigureThe life cycle of the new coronavirus and the mechanism of action of small molecule drugs, source: Sinolink Securities

US has approved new crown drug inventory

US has approved new crown drug inventory

According to incomplete statistics, a total of 10 new crown drugs have been approved or emergency authorized by the US FDA, including 4 small molecule drugs , including 1 3CL protease inhibitor, 2 RNA polymerase inhibitors, 5 neutralizing antibodies; antibody drugs 6 , including 5 neutralizing antibodies and 1 IL-6 receptor inhibit.

4 types of small molecule drugs and 6 types of antibody drugs

FigureThe US FDA approves or emergency authorizes a new crown drug

Paxlovid

Paxlovid

In the hot new crown oral drug track, Pfizer's Paxlovid is the most eye-catchi.

Paxlovid is composed of the 3CL protease inhibitor nematevir (PF-07321332) and ritonavir nelmatevir ritonavir

On April 14, the Phase II/III clinical data of Paxlovid were published in the New England Journal of Medici.

On April 21, the WHO issued new treatment recommendations for new coronary pneumonia, strongly recommending Paxlovid for the treatment of patients with mild or moderate new coronary pneumonia at high risk of hospitalizati.

FigurePaxlovid Phase II/III Clinical Trial Results

After obtaining the FDA's EUA approval on December 22, 2021, Pfizer immediately won an order of 20 million courses of treatment from the US governme.

On May 3, Pfizer announced its first-quarter resul.

Paxlovid's first-quarter sales of $47 billion were well below expectatio.

Monupavir

Molnupiravir, developed by Merck in cooperation with Ridgeback Biotherapeutics, is an RNA polymerase inhibitor that can bind to the RNA polymerase of the new coronavirus and introduce wrong nucleotides into newly synthesized RNA molecules, thereby inhibiting or The role of virus remov.

The drug is the world's first new oral drug approved for the treatment of mild to moderate adult patients

On November 26, 2021, Merck announced the phase III clinical data of monupavir, which showed a 30% reduction in the risk of hospitalization/death (8% vs 7.

In 2022, Monupiva is expected to generate sales revenue of US$5 billion to US$6 billi.

remdesivir

Remdesivir is the only drug officially approved by the FDA for use in hospitalized patients with COVID-1 Although its efficacy is controversial, the global sales of Remdesivir will reach US$56 billion in 2021, a year-on-year increase of 9
In the first quarter of 2022, Remdesivir sales increased by 15% year-on-year to $5 billi.

On April 25 this year, the FDA approved remdesivir as the first new crown therapy for infants and young children, which can be used for pediatric patients 28 days and older, weighing at least 3 kg and positive for the new coronavir.

Remdesivir is the only FDA-approved drug for hospitalized COVID-19 patients

Baricitinib

Baricitinib

Eli Lilly's autoimmune drug baricitinib is the only drug approved to treat severe cases of COVID- 19, reducing the risk of death by 3
The drug's annual sales in 2021 will reach US$115 billion, a year-on-year increase of 7
It is currently conducting a Phase III clinical study for the treatment of alopecia areata, and is expected to become the first FDA-approved drug for the treatment of alopecia area.

Baricitinib is the only drug approved for severe COVID-19

FigureStatistics on the distribution of new crown drugs in the United States, source: Huachuang Securities

Domestic new crown oral medicine is about to come out

Domestic new crown oral medicine is about to come out

There are currently 3 new crown drugs in China that have been approved by the Food and Drug Administration, namely Lianhua Qingwen Capsules/Granules from Yiling Pharmaceuticals, Neutralizing Antibody Ambavirumab/Romisevirumab from Tengsheng Biopharmaceuticals, and Pfizer's Small molecule oral drug Paxlov.

In view of the weakened efficacy of neutralizing antibodies in the face of mutant strains, the price of Paxlovid for a box of 2,300 yuan is hi.

In the face of the severe epidemic situation, we urgently need to have safe, efficient and affordable oral drugs for the new cro.

According to incomplete statistics, there are a total of 14 domestic new crown oral drug products under development, including 8 3CL protease inhibitors and 4 RNA polymerase inhibito.

FigureSome domestic new crown oral drug research projects

Azvudine

Azvudine

Real Bio's Azvudine is widely believed to be the first domestically produced oral drug for COVID-1 On April 2, the current status of the application for the real biological class III communication meeting on the website of the Center for Drug Evaluation was changed from "processing" to "reporte.

Azvudine is the world's first innovative anti-HIV drug approved for marketing in July 202 It has an antiviral effect by inhibiting the RNA polymerase of the new coronavir.

On April 16, Academician Jiang Jiandong introduced the research and development progress of Azvudine in the treatment of new crown indications at the China Medical Development Conferen.

From the clinical results of Phase II to Phase III, the patient's nucleic acid turned negative for 3-4 days after oral administration of azvudine, the average medication time was 6-7 days, and the average was 9 days for dischar.

The treatment effect of severe and mild cases was simil.

Compared with remdesivir, azvudine is orally 5 mg per day, compared with 100 mg of remdesivir injected daily, the clinical effect is significantly better than that of remdesivir

At present, the Phase III clinical trials of Azvudine in China, Brazil and Russia have ended, and it is in the stage of application for marketi.

It is worth noting that Azvudine has been specially approved to various embassies, volunteers for the Beijing Winter Olympics, troops stationed in Hong Kong, e.

, to provide more space for imagination for preventive medici.

The clinical effect is significantly better than that of remdesivir

On the evening of May 8, China Resources Shuanghe, who "still holds a pipa and half-covered his face", announced that the company signed the "Strategic Cooperation Agreement" and "Azvudine Film Entrusted Processing and Production Framework Agreement" with Real Life, and then China Resources Shuanghe May 9 and 10 ushered in a strong daily limit for two consecutive days, and Xinhua Pharmaceuticals, which had previously announced a strategic partnership with Real Bio, had a daily daily limit for nine consecutive days, which shows the enthusiasm of the capital market for "new crown oral drug.

In yesterday's article, Yaodu reviewed Azvudine and Xinhua Pharma in detail, Azvudine's "money capability", and brought Fei Xinhua Pharma: the daily limit rose for 9 consecutive days, and the stock price hit a new high! For readers' referen.

Azvudine's "money capability", with Fei Xinhua Pharmaceutical: The stock price has risen to a new high for 9 consecutive days!

VV116

VV116

On April 19, the website of the China Clinical Trial Registration Center announced the head-to-head, multi-center, single-blind, randomized, controlled phase III clinical study of Junshi Bio/Wangshan Wangshui VV116 and Pfizer Paxlovid in the early treatment of mild to moderate new coronary pneumon.

One stone stirred up a thousand wav.

The choice of VV116 is directly compared with the world's most effective new crown oral dr.

Once the result is non-inferior, it will greatly help VV116's approval and market prospec.

VV116 is chosen to be directly compared with the world's most effective new crown oral dr.

Once the result is non-inferior, it will greatly help VV116's approval and market prospec.

VV116 is jointly developed by Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Wuhan Institute of Virology, Chinese Academy of Sciences, Wangshan Wangshui Bio-Pharmaceutical .

, L.

and other institutio.

Clinical development and industrialization on a global sca.

On December 30, 2021, VV116 obtained emergency use authorization in Uzbekistan, which was based on a clinical trial of moderate and severe new coronary pneumonia completed by VV116 in Uzbekista.

And significantly reduce the risk of critical illness and dea.

Currently, a number of international multi-center Phase III clinical studies of VV116 for mild to moderate and moderate to severe COVID-19 patients are underw.

Studies have shown that VV116 can improve the clinical symptoms of patients, shorten the time to negative nucleic acid, and significantly reduce the risk of critical illness and dea.

FigurePhase III clinical study of Junshi Bio/Wangshan Wangshui VV116 and Pfizer’s Paxlovid

Prokluamide

Prokluamide

Prokalutamide is an androgen receptor (AR) antagonist, which may prevent the virus from entering host cells by inhibiting the expression of ACE2 and TMPRSS2, and activate the Nrf2 pathway to inhibit inflammatory facto.

In March 2021, Kintor announced that a clinical trial of severe new crown patients in Brazil showed that proclutamide could reduce the death risk of severe new crown patients by 92% and shorten the average hospital stay by 9 da.

The data is eye-catchi.

However, on December 27, 2021, Kintor Pharmaceutical announced that the Phase III clinical interim trial did not reach statistical significance, causing its stock price to drop by 8

On April 6 this year, Kintor Pharma announced the key data of the global multi-center Phase III clinical trial of proclutamide in the treatment of patients with mild to moderate COVID-1 The results show that proclutamide can effectively reduce the hospitalization/mortality rate of new crown patients, and the corresponding protection rate is 100% for the patient population who completed the medication for more than 7 da.

At the same time, proclutamide can significantly and continuously reduce the new coronavirus load and improve the symptoms related to the new cro.

Prokalutamide can effectively reduce the hospitalization/mortality rate of new crown patients, and the corresponding protection rate is 100% for the patient population who completed the medication for more than 7 da.

Entering the second half of the new crown epidemic, Azvudine from Real Bio, VV116 from Junshi Bio/Wangshan Wangshui, and Prolutamide from Kintor Pharma are the troikas running at the forefront, who will be the final Stand out, let's wait and see!

Outlook - seeking balance in dynamic adjustment and optimization

Outlook - seeking balance in dynamic adjustment and optimization

Up to now, the cumulative number of infected people in Shanghai has exceeded 600,000, which is equivalent to 3 people per 50 people living in Shangh.

Although we see hope for improvement, we have also paid a heavy pri.

We have to admit that after three years of tug-of-war with the new coronavirus, we still have not found an effective means to curb the spread of the epidemic, and there are still many unsolved mysteries waiting for researchers to unear.

"Dynamic clearing" is the current general policy of China's new crown pneumonia epidemic prevention and contr.

Its essence is speed and precisi.

"Dynamic" refers to not pursuing absolute zero infecti.

"Clearing" means finding and eradicating together, and guarding against outbrea.

The bottom line of a massive rebou.

How to effectively protect people's basic living needs while preventing and controlling the epidemic, and avoid the occurrence of "secondary disasters" and the negative impact on the economy to the greatest extent, it is necessary to coordinate closely with various departments, quickly and efficiently mobilize all available resources, and it is necessary to track the outbreak of the new coronavir.

Variation characteristics, to achieve "dynamic" adjustment and optimization of epidemic prevention strategi.