5 highlights of the national talk preliminary examination list! PD-1 opened a "roll" of large indications, and the sky-high price of CAR-T once again chased deer, focusing on rare diseases and pediatric medication

After the battle of the enterprise declaration stage, the list of drugs that passed the preliminary examination of the 2022 version of the national medical insurance catalogue was finally released

From this list, it can be seen that the adjustment mechanism of the national medical insurance catalogue, which is being optimized every year, has shown more and more scientific and refined characteristics

Among them, the first mention of children's drugs and rare disease drugs in the declaration conditions, and the relaxation of the corresponding access conditions and the cancellation of the condition of "approval after 2017", highlight the characteristics of

The domestic new crown oral drug azifrodine tablets and Pfizer nematvir tablets / ritonavir tablets appeared in the list of preliminary drug lists at the same time has become a "unique landscape", but it is worth mentioning that the azvedine is not declared as a "new crown drug", and its drug information shows that the indications for this drug are high viral load HIV-1 infection

According to the data of the National Medical Insurance Bureau, from 9:00 on July 1, 2022 to 17:00 on July 14, 2022, the national medical insurance information platform received a total of 537 enterprise declarations, involving 490 drugs; Among them, 344 drugs passed the preliminary form examination, and the proportion of passing was 70%; Compared with 2021 (271 of the 474 drugs passed), the number of drugs declared and passed the preliminary form examination has increased to a certain extent; In terms of pass rate, the proportion of drugs outside the list is 60%, and the proportion of drugs in the list is 91%.

Off-list drugs have always been the most likely areas for "sharp price reductions" in future health insurance negotiations, so they have also attracted much attention

What are the highlights of this year's preliminary list? The E drug manager sorted out

01 Focus on "small groups that don't give up"

To what extent can rare disease drugs benefit the population when they enter medical insurance?

After the 2021 medical insurance negotiations will be Bojian's "550,000 yuan a shot" spinal muscular atrophy (SMA) drug Nosinasan sodium "soul bargaining" to 33,000 yuan a needle, the newly released "China SMA Patient Quality of Life Study" shows that 76.

The attention to the rare disease group has also accelerated the speed of rare disease drugs entering the medical insurance list significantly, from approval to entry into the medical insurance directory the time from 87 months to an average of 18 months, and some drugs are even included in medical insurance

In 2022, with the relaxation of access conditions and the increasing clarity of rare disease policies, the enthusiasm of enterprises to participate in negotiations has also become increasingly high

In the preliminary review list of this year's medical insurance catalogue, there are 19 types of rare disease drugs that meet the conditions, including Laronise concentrated solution for injection and Aidou sulfase ß injection for mucopolysaccharide storage disease, offatumab injection for multiple sclerosis, dimethyl fumarate enteric-coated capsules, etc.

At the same time, in order to enter the medical insurance, the willingness of enterprises to reduce prices is also

Still taking SMA drugs as an example, after Bojian's Nocinachona sodium "fractured" into medical insurance last year, Roche, another pharmaceutical company approved as the "only two" in China, obviously can't sit still

Like rare diseases, children's medicine is a market

Since August 2011, the state has successively issued more than 30 policies involving the research and development of children's drugs, and issued three batches of lists to encourage the research and development of children's drugs, and the national medical insurance has also given a lot of policy preferences

The data shows that in 2017, 91 new pediatric drug varieties were added to medical insurance, and the number of drugs or dosage forms clearly applicable to children in the drug list increased to 540, further strengthening the protection of children's medication; The 2019, 2020 and 2021 editions of the medical insurance catalogue adjustment plan are also clear, focusing on adjusting and prioritizing the inclusion of pediatric drugs, and the average price of the 34 exclusive pediatric drugs negotiated and admitted in 2021 has reached 55.

In this preliminary list, there are also 11 children's drugs
.
The dosage forms are mainly oral solutions, granules and inhalants; In terms of sub-categories, anti-epileptic drugs, immunosuppressants, and anorexia drugs are the mainstays
.

02 CAR-T, ADC again set off a storm?

In addition to rare disease drugs, whether another type of CAR-T cell therapy, which can also be called "sky-high price", can enter medical insurance has also attracted much attention
.

Like last year, CAR-T also appeared again in this year's preliminary list, but the difference is that this year's preliminary list is WuXi Junuo's Ricky Olense injection (trade name: Benoda), not Fosun Kate's Agironsa injection (trade name: Ikeda).

This may be good news
for the recent WuXi Junuo.

On September 5, the Shenzhen Stock Exchange issued an announcement on the adjustment of the list of securities subject to the Hong Kong Stock Connect under the Shenzhen-Hong Kong Stock Connect, and WuXi Juno-B became one of the three Biotech companies that were transferred, the other two being Hebo Pharmaceutical-B and Genor Bio-B
.
Affected by this news, the share price of WuXi Juno fell by more than 30%
on the same day.

As the only company that has been listed on the market of three Biotech companies, WuXi Junuo recently disclosed in its financial report that the company's revenue in the first half of 2022 was 66.
007 million yuan, and a total of 77 Benoda treatment prescriptions were issued in the first half of the year, and 64 patients were reintroduced
for r/r LBCL patients.

Previously, it was reported that Benoda was priced at 1.
29 million yuan
.
Judging from the revenue disclosed by WuXi Junuo, the price of Benoda is indeed not low
.
It is not easy for high-priced drugs to enter the medical insurance directory, and the logic of "price for volume" in medical insurance negotiations may not be feasible
for CAR-T cell drugs.
At present, the approved CAR-T cell drugs are all autologous CAR-T cell therapies, which cannot achieve the production of multiple drugs at one time, and the cost cannot be reduced by mass production, and there are difficulties
in significant price reductions.
I don't know if Yi Kaida has not succeeded before, whether Benoda can achieve it
.

For some high-priced drugs to enter the preliminary examination list, the National Medical Insurance Bureau said that some of the more expensive drugs passed the preliminary formal examination, which only meant that the drugs met the declaration conditions and obtained the qualifications
for entering the next link.
Whether such drugs can eventually enter the national medical insurance drug list also needs to be strictly evaluated in many ways, including economy, and the exclusive drugs that pass the review must be negotiated, and the non-exclusive drugs must be bid, and only after negotiation or bidding can they be included in the list
.

In addition to CAR-T, the ADC dispute is also quite interesting this year
.

Among the ADC drugs that were listed in China last year, only Rongchang Bio's vidicetitizumab was successfully negotiated, Roche's enmetrytolizumab did not pass the preliminary list, and Takeda's vibutuximab was shortlisted but the negotiation failed
.

This year, Enmetrotolizumab also appeared on the preliminary list, and like Risperlan, Roche lowered the price of Enmetrotozumab twice as early as March and June of this year, with a cumulative decrease of more than 56%.

This means that it may be expected to compete with Takeda's vibutuximab for this year's health insurance negotiations this year, along with Takeda's vibutuxib, which is also on the preliminary list
.

03 PD-1 "Four Little Dragons": Concentrated "volume" large indications

In the 2022 PD-(L)1 negotiations, multinational pharmaceutical companies are all absent, and the competition
between the "Four Little Dragons" and the new ones is about to usher.

According to the information published in the preliminary medical insurance review list, the products of PD-1 "Four Little Dragons" Hengrui, BeiGene, Cinda and Junshi have all entered the preliminary review list of the medical insurance catalogue adjustment with the conditions 2 in the catalogue (drugs with major changes in indications or functional indications approved by the national drug regulatory authorities from January 1, 2017 to June 30, 2022
).

In terms of indications, this year is more volume than last year, the four companies hold 2-4 new indications declarations, the degree of competition is comparable to previous years, and this year's competition is more concentrated on the large indications, and the esophageal squamous cell carcinoma indications have become the "must-compete place"
for the four enterprises.

In addition to Junshi, the other three are intensively laying out various indications
for non-small cell lung cancer.
It is worth noting that from the end of 2021 to May this year, the four companies have successively approved the first-line treatment indications for advanced esophageal squamous cell carcinoma, which has also become the indications declared by the four companies in the adjustment of the medical insurance catalogue, and the fierce competition can be imagined
.

According to the Data of China Commercial Industry Research Institute, the number of new cases of esophageal cancer in China will reach 299,000 in 2021, with a compound growth rate of 3.
3% from 2017 to 2021, and it is expected that the number of new cases will continue to increase to 309,000 in 2022, with a compound annual growth rate of 3.
2%.

In addition, BeiGene, Hengrui and Junshi will compete on the same stage for the first-line treatment indications for nasopharyngeal carcinoma, of which Hengrui declared a first-line treatment
for patients with locally recurrent or metastatic nasopharyngeal cancer when the medical insurance catalogue was adjusted in 2021.
The first-line treatment indications for nasopharyngeal cancer in BeiGene and Junshi were only approved
in the first half of this year.

In addition, BeiGene has declared adult advanced solid tumor patients with non-resectable or metastatic microsatellite unstable (MSI-H) or mismatch repair gene defect type (dMMR): patients with advanced colorectal cancer who have developed disease progression after previous treatment with fluorouracil, oxaliplatin, and irinotecan; Indications for other advanced solid tumors that have developed disease progression after previous treatment and are not satisfactory with alternative treatment options
.
No PD-(L)1 inhibitors are available for this
indication.

Innovent also differentially reported first-line treatment
for non-resectable locally advanced, recurrent or metastatic gastric and gastric-duct junction adenocarcinomas.
The indication was approved
on June 23 this year.

In terms of price, the cost of PD-1 treatment dropped to an average of 40,000-45,000 yuan / year after the medical insurance negotiations in 2021
.
Then in the upcoming 2022 medical insurance negotiations, even if the PD-1 of multinational pharmaceutical companies does not appear in the preliminary review list, the "four little dragons" are not only facing competition with each other, but also to join several newly approved PD-(L)1, what kind of price will be refreshed this year, it is worth looking forward
to.

04 Imports no longer accompany the run, and the "new students" have different futures

PD-(L)1 is back.

There are PD-1 four musketeers with new suitors, and then there are several newly approved PD-(L)1s that are eager to try
.

There are five PD-(L)1s
approved for listing between June 30, 2021 and June 30, 2022.
Includes 3 PD-1s: Pieamprizumab from Chia Tai Tianqing/Kangfang Biologics, Cyprinumab from Yuheng Biologics/WuXi Biologics, and Slullimonumab from Henlius; With 2 PD-L1s: Corning Jerry/Simcere Pharmaceuticals/Emvoli maclizumab of Idea Di, Sugli maclizumab of CStone Pharmaceuticals
.

However, judging from the preliminary list, the newly approved PD-(L)1 has not rushed into the track
of health insurance negotiations.

In the 5 PD-(L)1, only Henlius' Slullizumab injection, Corning Jerry/Simcere Pharmaceuticals/Emvoli monoclonal antibody of Mind Di appeared, while Chia Tai Tianqing/Kangfang Bio's Pianprimab, Yuheng Bio/WuXi Biologics' Cyprinumab, and Cstone's Schuglizumab will not participate in this competition
.

In the PD-1 market, Henlius' H drug Slulimonab, as a latecomer, chose differentiated competition
in terms of indications.
In the first half of 2022, slulizumab was approved for use in microsatellite highly unstable (MSI-H) solid tumors
.
For the product, Fuhong Henlin is quite important, it is understood that Fuhong Henlin in the first quarter of this year for H drug to complete the completion of a sales team of about 200 people, from the "bidding access", "commercial channels", "price management" and other aspects, to promote H drug in the approval of the channel as soon as possible through various channels to benefit patients, full penetration of the Chinese market
.

In the PD-1 competition, the relevant person in charge of Henlius said in an interview with the E drug manager that the domestic PD-1 market pattern is far from fixed, and in the next three years, China's PD-1 market may be completely different from
now.
The key to the ultimate winner, or whether the latecomer can catch up, is that the product data should be good enough to become the standard treatment or the best treatment in the corresponding field; Secondly, the production quality is fully guaranteed, and the production cost is controllable; There is also a sound large-scale commercialization team
.

Although pisaprizumab will not appear at the scene of medical insurance negotiations, another product of Kangfang Bio, the first domestic dual antibody approved on June 29 this year, PD-1/CTLA-4 bispecific antibody new drug cardulinizumab, will debut in medical insurance negotiations
.

As a new generation of potential first-of-its-kind tetrameric bispecific antibody drugs, cardulinizumab is mainly based on KFone's proprietary Tetrabody technology
.
With this technical support, cardulinizumab can target PD-1 and CTLA-4 at the same time, and bind to tumor-infiltrating lymphocytes (TIL) tetravalents that co-express PD-1 and CTLA-4, blocking two immune checkpoint molecules in the tumor microenvironment, thereby reducing the tendency
of activated T cells to attack healthy tissues at peripheral sites.
Shortly after the approval of cardulinizumab, its price scheme also flowed out: 13220 yuan / 125mg / bottle, 3 bottles per dose, administered every two weeks
.
According to the pricing scheme and the patient assistance scheme, the annual treatment cost is close to 200,000 yuan, according to this scheme, some in the industry believe that the price has left room
for the upcoming medical insurance negotiations.

In addition, it is worth noting that 4 imported PD-(L) 1 pass are not eligible for this year's medical insurance negotiations
.
According to the preliminary list, Merck's pambolizumab (K drug), Bristol Squibb's navuliyumab (O drug), Roche's altelizumab (T drug), and AstraZeneca's duvallijumab (drug I) did not appear on the preliminary list
.

05 How will Biotech's first commercial product behave?

In 2022, more and more local biotechs enter the first year of
commercialization.
In the face of health insurance negotiations, entering or not entering, how to enter, is a choice
that biotech must make.

Judging from the results of the dynamic adjustment of the medical insurance catalogue in 2021, of the 67 successfully negotiated drugs outside the catalogue, 27 innovative drugs have achieved the results of entering the medical insurance in the year of listing, and there is no shortage of the first commercial products
of local biotech companies.
For example, Rongchang Bio's tetacil for the treatment of systemic lupus erythematosus injection, vidicetizumab for tumor drug injection, NovoInchen's BTK inhibitor obutinib tablets, and Aliss' vometinib mesylate tablets have been successfully included in the new medical insurance catalogue within one year of listing, providing a strong impetus
for the commercialization of its products.

In this year's preliminary review list, Yasheng Pharmaceutical, Corning Jereh, Kangfang Bio, etc.
will all enter the examination room
of medical insurance negotiations for the first time.

Corning Jereh welcomed its first commercial product
in November 2021.
On November 25 last year, NMPA conditionally approved the listing of Corning Jerry and Simcere Pharmaceuticals' Class 1 biological new drug Envolizumab Injection for the treatment of adult advanced solid tumor patients with unresectable or metastatic microsatellite highly unstable (MSI-H) or mismatch repair gene defect type (dMMR), including previously underwent fluorouracil, Patients with advanced colorectal cancer who develop disease progression after treatment with oxaliplatin and irinotecan, as well as other advanced solid tumors with disease progression after previous treatment and no satisfactory alternative treatment options
.
Envolizumab injection is the world's first subcutaneous PD-L1 inhibitor and the first domestic PD-L1 product
.

Yasheng Pharmaceutical also ushered in its first commercial product in November last year, the company's core variety, the original Class 1 new drug, the national "major new drug creation" special achievement orebatinib was approved for listing in China, for the treatment of any tyrosine kinase inhibitor (TKI) resistance, and the use of fully validated test methods to diagnose chronic myeloid leukemia (CML) chronic phase (CP) or accelerated stage (AP) adult patients
with T315I mutation 。 This is the first and only third-generation BCR-ABL inhibitor approved for marketing in China, filling the domestic clinical gap and breaking the previous survival dilemma
of cmL-resistant patients with T315I mutations.
At present, Asunit Pharma has established its own commercialization team and reached in-depth cooperation with Cinda to jointly promote the commercialization
of orebatinib in China.

As local biotech gradually enters the harvest period, the successful entry of drugs into medical insurance is conducive to its rapid release and accelerated commercialization
.
This is especially true for biotech companies that are not yet fully commercialized
.
Sending new drugs to medical insurance for the first time has become one of the indispensable actions in commercial expansion
.
Accelerating the launch and volume of new products through medical insurance negotiations, and realizing the effective cycle of research and development and re-investment, is the expectation
of all innovative pharmaceutical companies for medical insurance.
For companies that have just achieved the first commercialization or only 1-2 listed products, the rapid release will also achieve capital repatriation and faster recovery of research and development costs
.