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Mobocertinib

Generic Name
Mobocertinib
Brand Names
Exkivity
Drug Type
Small Molecule
Chemical Formula
C32H39N7O4
CAS Number
1847461-43-1
Unique Ingredient Identifier
39HBQ4A67L
Background

Mobocertinib is a kinase inhibitor targeted against human epidermal growth factor receptor (EGFR). It is used specifically in the treatment of non-small cell lung cancer (NSCLC) caused by exon 20 insertion mutations in the EGFR gene, which are typically associated with a poorer prognosis (as compared to "classical" EGFR mutants causing NSCLC) and are associated with resistance to standard targeted EGFR inhibitors. Mobocertinib appears to be an effective means of treating this otherwise treatment-resistant NSCLC, exerting an inhibitory effect on EGFR exon 20 insertion mutant variants at concentrations 1.5- to 10-fold lower than those required to inhibit wild-type EGFR.

Mobocertinib, under the brand name Exkivity (Takeda Pharmaceuticals Inc.), was granted accelerated approval by the FDA in September 2021 for the treatment of locally advanced or metastatic NSCLC in patients with EGFR exon 20 insertion mutations who have failed previous therapies.

Indication

Mobocertinib is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

Associated Conditions
Locally Advanced Non-Small Cell Lung Cancer, Metastatic Non-Small Cell Lung Cancer
Clinical Trials
Related News

FDA Approves Takeda's Exkivity as First Oral Therapy for EGFR Exon20 NSCLC

• Takeda's Exkivity (mobocertinib) receives FDA approval as the first oral therapy specifically designed for NSCLC patients with EGFR exon20 insertion mutations after chemotherapy. • Clinical trials demonstrated Exkivity's efficacy with 28% tumor shrinkage rate and median progression-free survival of seven months in treated patients. • The approval strengthens Takeda's Wave1 pipeline portfolio, with the drug projected to reach $600 million in peak sales pending potential first-line treatment approval.

Inspector General Report Flags FDA's Accelerated Approvals of Aduhelm, Exondys, and Makena

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RYBREVANT and LAZCLUZE Combination Shows Significant Survival Improvement in EGFR-Mutated NSCLC

• Johnson & Johnson's RYBREVANT plus LAZCLUZE demonstrates statistically significant and clinically meaningful improvement in overall survival (OS) versus osimertinib in EGFR-mutated NSCLC. • The MARIPOSA Phase 3 study showed the chemotherapy-free combination is expected to improve median OS by over one year compared to the current standard of care. • RYBREVANT plus LAZCLUZE is approved in the U.S. and Europe as a first-line therapy for NSCLC patients with EGFR exon 19 deletions or L858R substitution mutations. • The safety profile of the combination was consistent with individual treatments, with venous thromboembolic events managed through prophylactic anticoagulants.

FDA's Accelerated Approval Pathway Faces Scrutiny Amidst Withdrawals and Biomarker Concerns

• The FDA's accelerated approval program, designed to expedite drug availability, faces increased scrutiny due to recent high-profile withdrawals, including Pfizer's Oxbryta. • Experts are raising concerns about the reliability of surrogate endpoints and the timeliness of confirmatory trials required for maintaining accelerated approvals. • There is a call for better understanding and validation of biomarkers used in accelerated approvals, especially in complex diseases like Alzheimer's and ALS. • Proposed solutions include stricter deadlines for confirmatory trials and addressing potential biases in the FDA's funding structure to ensure unbiased judgment.

FDA's Accelerated Approval Pathway Faces Scrutiny as Some Drugs are Withdrawn

• Several drugs approved under the FDA's accelerated approval pathway have been withdrawn from the market due to safety concerns or failure to confirm clinical benefit. • Pfizer pulled Oxbryta, a sickle cell disease therapy, after new data showed a higher risk of deaths and complications in treated patients. • Biogen and Eisai discontinued Aduhelm, an Alzheimer's drug, after a controversial approval and inauspicious rollout, focusing instead on Leqembi. • The FDA is now requiring confirmatory trials to be underway before granting accelerated approval to address delays and ensure clinical outcomes.
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