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Takeda's lung cancer drug has been approved for marketing in China for only one rare mutation, but some patients really need it

 Last Update: 2023-02-01
 Source: Internet
 Author: User

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Source: NMPA official website

preface

On the evening of January 11, 2023, Takeda China announced that its Mobocertinib (Mobocertinib succinate capsules, hereinafter referred to as "Mobocertinib ®") has been approved by the National Medical Products Administration (NMPA) to officially enter China
.

Adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are still undergoing or progressing after platinum chemotherapy and carry an epidermal growth factor receptor (EGFR) exon 20 insertion mutation may not be able to sleep
tonight.
(Healthy us, can't achieve true empathy)

They are a group of lung cancer patients who have suffered from the disease, and they have the "lung cancer"
that each of us is familiar with.
But the epidermal growth factor receptor (EGFR) exon 20 insertion mutation seems a little strange, what does the approval of mobosetinib mean? And what can this drug bring to these (patients)?

01 I received a genetic test report

When the author is working in the clinic, patients are often asked, "Doctor, what do you think of this genetic test report, do I have any diseases?" "In fact, genetic testing is the technology of testing DNA through blood, other body fluids or cells, so that people can understand their genetic information
.
So as to improve their living environment and living habits, and achieve the purpose of avoiding or delaying the occurrence of
diseases.
For a person with tumor, genetic testing can help patients
in multiple dimensions such as tumor heritability, chemotherapy medication guidance, tumor individualization medication guidance, etc.
Just like the EGFR exon 20 insertion mutation (EGFR) above ex20in), we can find targeted drugs
for patients in the widest range of applications through genetic testing.
EGFR ex20in, an "uncommon mutation" of EGFR, a common target of non-small cell lung cancer (NSCLC
).
Its incidence accounts for about 2.
3% of all NSCLCs in China and is known as a "rare target"
.
EGFR The EX20IN has a special structure
.
The EGFR gene consists of 28 exons on chromosome 7, of which exon 20 is responsible for transcribing amino acids at the E762-K823 location, including the C-helix composed of E762 to M766 codons and the loop
composed of A767 to V774 codons.
This is an EGFR when the insertion mutation of tumor formation occurs in the E762 to M766 and A767 to V774 codons ex20in
。 After understanding the principle, when we see that the genetic test report says A763_Y764insFQEA, it means that there is an insertion mutation between the A763 and Y764 codons, that is, EGFR ex20in
。 Its special structure is because of EGFR The insertion of 20 exons changes the structure and forms steric hindrance, resulting in a smaller drug-binding bag and the drug can no longer bind
to the target.
It also directly leads to the poor prognosis of this group of patients, compared with classic EGFR mutations The survival benefit is significantly reduced
in patients with EX20ins mutations.

02 One in summer and one in winter

EGFR was analyzed in a retrospective cohort study of patients with common EGFR versus EGFR ex20ins mutations EGFR was used in patients with advanced NSCLC (n=76) and common EGFR mutations (n=2749) with ex20ins mutations The predictive value of TKI (the standard first-line treatment regimen for patients with EGFR gene mutation NSCLC) treatment shows:

EGFR ex20ins vs common EGFR mutant TKI for PFS

Compared with common EGFR mutations, patients with EGFR ex20ins mutations had a 169% increased risk of progression or death after TKI treatment;

Compared with common mutations, patients with EGFR ex20ins mutations had significantly shorter median progression-free survival (PFS) treated with TKI (2.
9 months vs.
10.
5 months, p<0.
0001), 1-year PFS rate was significantly lower (13% vs 43%);

Patients with EGFR ex20ins mutations had a 170% increased risk of death compared with common EGFR mutations;

Patients with EGFR ex20ins mutations have a 154%
increased risk of needing to change treatment compared with common EGFR mutations.

At present, there are 8 approved EGFR TKIs in China
.

Source: Frost & Sullivan, Industrial Securities Economics and Inclusive Research Institute, but none of these EGFR inhibitors have been approved for ex20ins mutation indications, and through several small clinical trials, it can be found that their efficacy in ex20ins mutation patients is very limited, or not ideal
.

Generation EGFR-TKI: gefitinib (objective response rate ORR: approximately 8%; mPFS: <3 months)

Second-generation EGFR-TKI: afatinib (ORR: 8.
7%; mPFS: 2.
7 months)

Third-generation EGFR-TKI: osimertinib 80 mg (ORR: 5%; mPFS: 3.
6 months)

Therefore, for a long time in the past, the first-line standard treatment for patients with EGFR ex20ins mutations was platinum-based chemotherapy, after all, the effect of chemotherapy is better
.
For EGFR For ex20ins mutation patients, they really can't sleep
tonight.
The approval of mobosetinib in China has alleviated a large number of unmet clinical needs to a certain extent and filled the gap
of clinical treatment in China.

03 A hundred flowers bloom and several enemies stand up

In fact, as early as September 15, 2021, the FDA accelerated the approval of the marketing of Mobocertinib; In fact, earlier, the FDA had approved a specific treatment for EGFR EX20INS targeted drugs
.

On May 21, 2021, the FDA accelerated approval of Johnson & Johnson's Rybrevant (JNJ-372) for the treatment of progression, EGFR after failure of platinum-containing chemotherapy Adult patients
with non-small cell lung cancer with exon 20 insertion mutations.
The two drugs have been approved one after another, and they are both in this blank field, which inevitably arouses everyone's curiosity, which is their "better or worse"?

Interestingly, Amivantamab's ORR has a wide disparity of 41% vs 25% (corresponding to "proximal loop insertion mutation" and "distal ring insertion mutation"), which means that the patient's mutation subtype
may need to be considered when using Amivantamab clinically in the future.
Currently, the 2022 edition of the CSCO guidelines for non-small cell lung cancer has included Amivantamab and Mobocertinib as EGFRs exon20ins Grade III recommended regimen
for post-line treatment of NSCLC.
Domestically, Ditze Pharma announced on January 10, 2023 that its new drug marketing application for suvortinib tablets (DZD9008) was accepted by the NMPA and included in the proposed priority review
.
Suvortinib (DZD9008) in EGFR exon20ins NSCLC Excellent research results have also been achieved, with an ORR of 59.
8% at the dose level of 300mg, and the efficacy of brain metastases is outstanding
.
At the 2022 ASCO Conference, Ditze Pharma announced the sale of 100 mg The overall response rate (ORR) was also 41% in the subgroup with a BID dose level and a median PFS of 12 months
.
In addition, Zai Lab's CLN-081, Junjing's AP-L1898, and Fuwo Pharmaceutical's FWD1509 MsOH has been clinically studied
.
It is really better than a "better or worse", but also from the size of the adverse reaction; Control effect on brain metastases; Whether to all EGFRs Ex20ins mutation types are effective; drug resistance mechanisms; Whether it has better medication convenience and compliance and other dimensions to consider
.
For the current domestic patients, it is effective for me, I buy, I buy, and the side effects are not big, it is a good medicine!

04 The summary is good, and the future can be expected

The drug still has to return to the patient, and for the enterprise, it is back to the user's
ability to pay.

It is reported that a 350mg/7mL Rybrevant is priced at $3,127, about 20,000 yuan
.
According to the recommended usage, patients weighing less than 80kg need 240,000 yuan for the first month of using Rybrevant, and 120,000 yuan per month for subsequent months; Patients weighing more than 80 kg cost 320,000 yuan in the first month and 160,000
yuan per month thereafter.

As for Mobocertinib, the specification is 120 capsules of 40 mg, the reference price is 210870 yuan; The standard dosage is 160 mg orally once daily , a meal of 7029 yuan ??

However, in some overseas purchasing, there may be cheap, TAK-788 Hong Kong clinical version, specification 40mg * 30 tablets, price 7500 yuan, excluding customs
clearance.

In any case, it is unaffordable for me, and I believe that for most families, it is the same
.

Like the previous two PD-1 inhibitors, Keytruda and Opdivo, they were initially sky-high, but after entering the country, the price was directly reduced
.
Although neither of the subsequent drugs was included in Medicare, Merck and BMS both updated their respective patient assistance programs
.

Well, now mobosetinib is approved
in China.

"What about pricing? Can I get into Medicare? When do I get into Medicare? A patient with an EGFR ex20ins mutation thought
.

References:

References: References:

1.
Major breakthrough! The world's first oral targeted drug "Mobosetinib" for the treatment of EGFR exon 20 exon 20 with mutation in advanced non-small cell lung cancer was approved in China! (Takeda China)

2.
EGFR exon 20 inserts mutation-refractory targets and adds new drugs, and the efficiency is increased by more than 3 times! (Zhihu: Medical Science)

3.
All-round popular science tumor genetic testing! (Zhihu: cancer)

4.
[2022 ESMO] Break the cocoon into a butterfly and | to the new Professor Wang Zhijie: EGFR ex20ins has added new evidence in the field of non-small cell lung cancer treatment! (Medical Oncology Channel)

5.
[3411] Professor Lu Shun| 2022 year-end inventory· EGFR Exon 20 inserts mutant advanced NSCLC, the exploration never stops (Tumor Information)

6.
[3369] [2022 CSCO] Breaking the cocoon into a butterfly and being born to the forest┃ Asian data announced! Amivantamab opens a new era of EGFR targeted therapy for advanced lung cancer! (Oncology Information)

7.
They are all EGFR mutations, and the "fate" is very different (respiratory channel in the medical community)

8.
Rare mutation in EGFR - exon 20 insertion mutation (Zhihu: peace of mind)

9.
From refractory to breakthrough, EGFR 20 exon insertion mutations are being overcome (Penguin: The Financial World)

10.
The first EGFR20 exon mutant lung cancer "oral targeted drug" - mobotinib is expected to be marketed in China (Penguin: Medical Companion Travel)

11.
Other public information

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