"Desperate bet" head-to-head test, what bet will domestic new drugs take tomorrow?

Drug development is often a follow-up

Drug development is often a follow-up

Choosing "head-to-head" is a time-consuming and risky challenge, but it is sometimes inevitable

The more important purpose of domestic new drugs is to open up overseas markets, especially the US market

For domestic new drugs, the head-to-head test is a heroic feat of desperate bets, so what bet will domestic new drugs take tomorrow?

PD-(L) 1 head-to-head K drug

PD-(L) 1 head-to-head K drug

Everyone says that PD-(L)1 is the "king of the inner volume", but there is still no shortage of pharmaceutical companies to enter this track

At present, there are 14 PD-1/PD-L1 drugs approved for marketing in China, 10 PD-1 inhibitors (8 domestic, 2 imported), and 4 PD-L1 inhibitors (2 domestic, 2 imported).

In addition, on March 7, 2022, Chia Tai Tianqing registered the launch of the phase III clinical trial of PD-L1 monoclonal antibody TQB2450 sequential combination therapy for the treatment of advanced nonsquamous non-small cell lung cancer, head-to-head Tiburizumab

Among the 7 domestic head-to-head K drugs, Cinda was the first to register and the first to publish clinical data

Junshi and Pfizer's oral COVID-19 oral drug are head-to-head

Junshi and Pfizer's oral COVID-19 oral drug are head-to-head

On May 23, 2022, Junshi Biotech announced that its oral nucleoside anti-SARS-CoV-2 drug VV116 tablets, developed in collaboration with Suzhou Wangshan Wangshui Biology, met the primary endpoints

The head-to-head clinical trial actually enrolled 822 patients, with primary study endpoints of "time to sustained clinical recovery" and secondary study endpoints including "percentage of participants who progressed to COVID-19 progression (defined as progression to severe/critical COVID-19 or all-cause death) as of day 28"

It is understood that there are currently more than ten new coronavirus small molecule drugs under research in China

VV116 is currently the only domestic small molecule drug

Compared with Paxlovid, whether it is the treatment effect, safety, price, etc.

Head-to-head of third-generation BTK inhibitors

Head-to-head comparison

Head-to-head comparison

In addition, Eli Lilly's LOXO-305 is a new generation of BTK inhibitors for the BTK C481S mutation under research, and it is confident

In the BRUIN MCL-321, Eli Lilly's LOXO-305 is a domineering, head-to-head PK of 3 BTK inhibitors
that have been listed.
In THE BRUN MCL-321, three-on-one, head-to-head PK is a listed 3 BTK inhibitors
.

The primary endpoint of this study was presented at the 27th Annual Meeting of the European Society of Haematology (EHA) in June 2022 as a Progression-Free Survival (PFS) based on the Lugano criteria assessed by the Blind Independent Center Review (BICR).

European Hematology Association ()

The open-label, global, Phase 3 trial will enroll approximately 500 patients randomized at a 1:1 ratio of 200 mg of oral pirtobrutinib once daily or the investigator-selected ibutinib (Imbruvica), akatinib (Calquence), or zebutinib (Brukinsa).

。 Stratification factors include the simplified MCL International Prognosis Index risk group (moderate-risk vs high-risk), the expected BTK inhibitors by control (ibutinib vs acalabrutinib/zebutinib), and the number of previous treatment lines (1 vs 2 or more).

Akatinib (

Currently, the BRUIN-MCL-321 trial is an ongoing study that is actively recruiting patients, and data will be released
at a later date.

Currently, the BRUIN-MCL-321 trial is an ongoing study that is actively recruiting patients, and data will be released
at a later date.

In March 2022, Cinda and Eli Lilly reportedly entered into a strategic partnership in which Cinda was given the right of first refusal to negotiate the future commercialization rights of Pirtobrutinib (LOXO-305) in Chinese mainland
.

Head-to-head of third-generation EGFR inhibitors

Head-to-head of third-generation EGFR inhibitors

Osimitinib is one of the representatives of the third-generation EGFR inhibitor, which jumped from second-line to first-line, and was also through a "head-to-head" clinical trial FLAURA trial
that directly compared efficacy with the first-generation EGFR inhibitor erlotinib/gefitinib.
In the FLAURA trial, osimertinib demonstrated excellent efficacy that comprehensively surpassed the first generation of EGFR inhibitors
.

At the European Congress on Lung Cancer (ELCC) in 2022, a third-generation EGFR inhibitor vometinib from China published the results
of a FURLONG trial comparing the efficacy of gefitinib "head-to-head" results.
In this trial, vometinib also surpassed gefitinib across the board, demonstrating excellent first-line therapeutic potential
.

Currently, among the third-generation EGFR inhibitors, there are three drugs that have undergone "head-to-head" trials with the first-generation drugs: AstraZeneca's osimertinib, Howson Pharmaceutical's Ametinib, and Aliss's vometinib
.
All three drugs have almost "doubled" the first generation of drugs, and the advantages are very significant
.
This is shown in
the following chart.

Currently, among the third-generation EGFR inhibitors, there are three drugs that have undergone "head-to-head" trials with the first-generation drugs: AstraZeneca's osimertinib, Howson Pharmaceutical's Ametinib, and Aliss's vometinib
.
All three drugs have almost "doubled" the first generation of drugs, and the advantages are very significant
.

In addition, the head-to-head PHASE III IOGEN trial of Exetinib and Gefitinib by Beda Pharmaceuticals is the world's first directly controlled study
between epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).
The results of the trial showed that exetinib was non-inferior in the median PFS index (4.
6 months vs 3.
4 months), and the drug-related adverse events caused by extinib were lower than gefitinib (61% vs 70%)
.
Compared with gefitinib, exetinib has the same efficacy and fewer toxic side effects
.

Other supplements

Other supplements

In addition to the head-to-head trials in the above blockbuster areas, there are some additions, as shown in the chart
below.

summary

summary

The development of new drugs is divided into two categories, one is the first in class, and the other is the improved new drug (me too
).
For innovative drugs, there are no head-to-head trials
because there are no known effective drugs to treat the disease.
However, if a valid drug for this indication already exists on the market, a positive control (head-to-head trial)
is required.

For innovative drugs, there are no head-to-head trials
because there are no known effective drugs to treat the disease.

Do head-to-head experiments with courage and hard medicine
.
Once the trial does not achieve positive results, it is likely that the new drug will be done in vain
.
Because the challenge fails in the first place, it is impossible to prove that the challenger is the second place, nor can it prove that the challenger is qualified
.
Therefore, it is not only courage that can do it, but also excellent technology to initiate head-to-head experiments
.

Do head-to-head experiments with courage and hard medicine
.
Once the trial does not achieve positive results, it is likely that the new drug will be done in vain
.

It can be seen that the domestic pharmaceutical companies that dare to be head-to-head are very confident!

If there is any omission in the above content, friends are welcome to share the supplement together
.