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Brazil April 2024 Drug Approvals | ANVISA | News | Media | iPharmaCenter

Updated: May 18

16, April 2024

Rybrevant is approved in Brazil for locally advanced or metastatic non-small cell lung cancer

Rybrevant (amivantamab) is approved for use with carboplatin and pemetrexed to treat adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that exhibits exon 19 deletions or L858R substitutions in exon 21 of the epidermal growth factor receptor (EGFR) and has progressed following treatment with a third-generation tyrosine kinase inhibitor (EGFR TKI).

This medication is also approved for the following uses:

  • Combined with carboplatin and pemetrexed, as an initial treatment for adults with locally advanced or metastatic NSCLC characterized by EGFR exon 20 insertion mutations.

  • As a standalone treatment for adults with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations that have progressed following platinum-based chemotherapy.


Lung cancer is one of the most prevalent cancer types and the leading cause of cancer-related deaths globally. Non-small cell lung cancer (NSCLC) makes up about 85% of lung cancers, with 5-year survival rates for NSCLC varying based on the stage at diagnosis, ranging from 65% for localized cancer to 9% for cancer that has metastasized.


In metastatic cases, driver mutations are found in around 60% of adenocarcinomas. Among patients with NSCLC adenocarcinoma, EGFR activation mutations are prevalent, occurring in approximately 15% of Western patients and up to 40%-50% in Asian patients. The most common EGFR mutations, Exon 19del and L858R, are identified in 80%-85% of patients with activating EGFR mutations.


The current treatment standard for NSCLC with mutated EGFR is osimertinib, a third-generation tyrosine kinase inhibitor (EGFR TKI) that has shown improved progression-free survival (PFS) and overall survival compared to first-generation TKIs. However, nearly all patients eventually develop resistance to osimertinib. Resistance mechanisms are diverse and often involve alterations in the MET gene (up to 51% by fluorescence in situ hybridization) and EGFR mechanisms. Treatment guidelines recommend platinum-based chemotherapy (carboplatin and pemetrexed) as the next step, with a historical median PFS of 4.4 to 5.5 months for patients with disease progression post-TKI treatment.


Due to the limited effectiveness of current treatments, the company explored the potential of their product to meet these medical needs.

Rybrevant is a targeted bispecific antibody approved for treating EGFR exon 20ins NSCLC after first-line platinum-based chemotherapy. It has demonstrated efficacy in two highly resistant NSCLC scenarios.


To further assess its effectiveness and safety, the company conducted the MARIPOSA-2 phase 3 study. This global, randomized phase III trial evaluated the efficacy and safety of amivantamab combined with carboplatin and pemetrexed (ACP) compared to carboplatin and pemetrexed alone (CP) in patients with EGFR-mutated NSCLC that progressed after osimertinib treatment.


Results from the MARIPOSA-2 study showed that the ACP combination significantly improved clinical outcomes compared to the standard CP therapy in patients with EGFR-mutated NSCLC who had progressed on osimertinib.


With a median follow-up of 8.97 months for the ACP arm and 8.34 months for the CP arm, ACP treatment led to a statistically significant and clinically meaningful improvement in the primary PFS endpoint as assessed by an independent, blinded central review committee. This PFS benefit extended beyond the median, with higher event-free rates at 6, 9, and 12 months in the ACP group compared to the CP arm.

Additionally, 51.5% of patients in the ACP arm continued therapy, compared to 22.6% in the CP arm. Other secondary outcomes also indicated disease improvement compared to the comparator treatment.


The safety profile of the ACP combination was consistent with known profiles of its components. Adverse events were generally manageable with protocol-specified dose adjustments and supportive care, with no new safety concerns identified. Most Grade 3 rashes occurred within the first three months of treatment. The incidence of adverse events increased modestly over 12 months, with an average rash grade 1-4 adverse event rate of 1.27 for CP and 1.72 for ACP. Differences in most adverse events of special interest between treatments stabilized or increased slowly over time. Given the evidence provided, the benefit-risk balance for this indication is considered positive.


 

Entyvio was approved in Brazil for severe chronic pouchitis

Entyvio approved for adult patients experiencing moderate to severe chronic pouchitis in its active phase, particularly those who have undergone a proctocolectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, and who have not responded adequately to or have lost response to antibiotic treatment.


Intravenous vedolizumab offers notable clinical advantages and meets a critical need for patients with pouchitis, a condition for which effective treatments are limited. For individuals with ulcerative colitis (UC), the surgical removal of the colon and rectum (proctocolectomy) often necessitates the creation of an ileal pouch to maintain stool control, known as ileal pouch-anal anastomosis (IPAA). While IPAA can also be performed for the rare premalignant condition familial adenomatous polyposis (FAP), pouchitis is more commonly reported in patients who have IPAA due to UC rather than FAP.


Acute pouchitis affects about 50% of UC patients with IPAA, usually responding to one or more courses of antibiotics; however, 10% to 15% of these patients may develop chronic pouchitis. Pouchitis is classified as treatment-responsive or treatment-refractory based on the response to antibiotic monotherapy. Those with chronic pouchitis who do not respond to standard treatments continue to suffer symptoms, which can result in pouch failure. Uncontrolled pouchitis significantly impacts patients’ work, home life, and social interactions.


Current treatments for chronic pouchitis, including antibiotics and inflammatory bowel disease (IBD) therapies, are used to induce and maintain remission. However, repeated antibiotic courses can lead to side effects, dependency, or resistance.

Steroids are recommended only for short-term use, and long-term data supporting immunosuppressants are scarce. While antitumor necrosis factor (TNF) treatments show short-term efficacy, their long-term benefits in chronic pouchitis are limited.

Moreover, the effectiveness of anti-TNFs may be reduced due to immunogenicity issues from previous exposures, potentially leading to decreased response or infusion reactions. Overall, the long-term benefits and effectiveness of antibiotics, probiotics, and other treatments for pouchitis remain uncertain.


Patients who respond well to antibiotics generally maintain a good quality of life, but those who do not may experience severe symptoms such as increased stool frequency, pain, depression, reduced satisfaction in social roles, and fatigue. Additionally, older age at the time of IPAA may negatively impact functional outcomes and quality of life. Long-term cohort studies indicate that inflammatory complications post-IPAA significantly burden patients after colectomy, with many fearing further surgery, having their pouch removed, and ending up with a permanent ileostomy. Consequently, there is a significant unmet need for effective treatments for this condition.


The Vedolizumab-4004 Study utilized a randomized, placebo-controlled design in a population of patients with antibiotic-refractory pouchitis. The primary analysis results of this study are robust, supported by sensitivity and subgroup analyses consistently showing the benefit of vedolizumab over placebo. Furthermore, secondary and exploratory endpoints also indicate vedolizumab's advantages compared to placebo, reflecting internal consistency.


These study results are corroborated by existing literature, which, although limited, provides additional evidence of vedolizumab's benefits in small studies and clinical experiences for treating chronic pouchitis unresponsive to antibiotics. Lastly, the plausibility of vedolizumab in treating chronic pouchitis is supported by its mechanism of action and pharmacological rationale, confirmed by its known effects demonstrated in phase 3 studies for UC and Crohn's disease.


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