CHMP Advances Seven Drugs but Differentiation Hinges on Safety and Payer Limits

CHMP Recommends Seven New Medicines and Eleven Indication Extensions

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) concluded its November 2026 meeting by recommending seven new medicines for marketing authorization in the EU. Additionally, the committee adopted positive opinions for extending the therapeutic indications of eleven existing medicines. Key new recommendations included Aumseqa (aumolertinib) for non-small cell lung cancer, Baxfendy (baxdrostat) for hypertension, and Zybrivo (sintilimab) for non-squamous non-small cell lung cancer. The meeting also saw positive opinions for two biosimilars (Garzulys, Donrafylix for diabetes) and two generics (Fondaparinux sodium Evumed, Ruxolitinib Krka).

• The CHMP issued positive opinions for seven new medicines, including Aumseqa (aumolertinib) for non-small cell lung cancer, Baxfendy (baxdrostat) for hypertension, and Zybrivo (sintilimab) for non-squamous non-small cell lung cancer. These recommendations also encompassed two new biosimilar insulins, Garzulys and Donrafylix, for diabetes mellitus, and two generic medicines, Fondaparinux sodium Evumed and Ruxolitinib Krka, addressing conditions like venous thromboembolic events, myelofibrosis, and Graft-versus-host disease.
• The committee recommended extending the use of eleven already authorised medicines. Notable extensions include Gazyvaro (obinutuzumab) for moderate-to-severe active systemic lupus erythematosus, allowing patients to reduce corticosteroid use, and Isturisa (osilodrostat) for endogenous Cushing’s syndrome in adolescents and children aged six years and older. These extensions aim to address unmet medical needs and improve treatment options for various patient populations.
• Beyond approvals, the CHMP confirmed its recommendation to refuse marketing authorisation for KemSu (sufentanil/ketamine) for acute pain and Meplyffa (arimoclomol citrate) for Niemann-Pick disease type C following re-examination. Applications for Amlypave (anselamimab) for kappa light chain amyloidosis and Qezzaqar (catequentinib) for soft tissue sarcoma were withdrawn. Additionally, a direct healthcare professional communication was adopted for Mounjaro (tirzepatide), advising on its potential effect on oral contraceptive reliability.
• The CHMP also issued a positive opinion for a new strength of the Dapivirine Vaginal Ring (dapivirine), enabling three-month replacement for HIV-1 prevention in women aged 16 and older. This assessment was conducted under the EU-Medicines for all (EU-M4All) regulatory procedure, highlighting EMA's role in supporting global regulatory capacity building and public health initiatives beyond the EU, with participation from WHO and national regulators from Kenya, South Africa, and Zambia.

Addressing Key Challenges in Non-Small Cell Lung Cancer Treatment

Current treatment approaches for NSCLC have improved outcomes but remain constrained by resistance, toxicity, and patient-selection challenges. The 5-year survival rate for advanced non-small cell lung cancer (NSCLC) is only 20%-30%, reflecting limited durability and unpredictable response across targeted and immune-based regimens.

• Heterogeneous acquired resistance to KRAS G12C inhibitors: Responses occur only in a fraction of patients, and among responders acquired resistance invariably develops over time. Mechanisms are heterogenous including on-target resistance such as secondary codon 12 KRAS mutations, acquired codon 13 and codon 61 alterations, and mutations at drug binding sites, and off-target resistance from activating mutations in KRAS downstream pathway (e.g., MEK1), acquired oncogenic fusions (EML4-ALK, CCDC176-RET), gene level copy gain (e.g., MET amplification), or oncogenic alterations in other pro-proliferative and antiapoptotic pathways (e.g., FGFR3, PTEN, NRAS), plus bypass pathway activation and adaptive reactivation of downstream MAPK signaling, with histologic transformation contributing in a fraction of patients.

• Unpredictable immunotherapy benefit and systemic toxicity: The treatment response of immune checkpoint inhibitors (ICIs) is not stable and unpredictable, and antibodies blocking PD-1/PD-L1 interaction can cause systemic adverse effects including adverse events (AEs) of grade 3 or higher, AEs leading to treatment discontinuation, serious AEs, and immune mediated AEs of any grade and of grade 3 or higher. Treatment-related hepatotoxicity, particularly in the setting of prior or closely sequenced immune checkpoint inhibitor exposure, has emerged as an important clinical concern for KRAS G12C inhibitors, while low PD-L1 copy number tumors display reduced PD-L1 expression, reduced PD-L1 tumor cell staining, and an immunologic cold tumor microenvironment where low copy number may predict lack of response.

• Central nervous system progression and detection limits: Brain metastasis is a common and lethal complication of NSCLC, mostly diagnosed only after symptoms develop, at which point very few treatment options are available. Tissue biopsy is challenging in isolated central nervous system progression, the blood-brain barrier prevents circulating tumor DNA (ctDNA) from entering the blood, and detection rate of genomic alterations in plasma ctDNA is lower in isolated CNS disease, with ctDNA positive in 52% iCNS versus 84% in noCNS and 92% in cCNS, with lower detection of driver and resistance alterations.

• Lack of consensus for poor-risk and molecularly heterogeneous populations: There is no consensus on the therapeutic approach to poor-risk patients with unresectable stage III NSCLC, where advanced age, poor performance status, weight loss and comorbidities influence treatment options and disease outcomes, and only two phase III studies specifically including poor-risk patients have been published. Implementation is further constrained by limited tissue availability, spatial heterogeneity, unstandardized assays, and combination toxicity, with molecular and spatial heterogeneity including KRAS co-mutations with STK11 and KEAP1 and KEAP1 mutation rate significantly higher in patients with brain metastasis than those without.

How NSCLC Treatment Has Evolved Over Five Years

Resectable non-small cell lung cancer (NSCLC) has shifted from surgery plus adjuvant chemotherapy, which provided only an approximate 5% improvement in 5-year overall survival and a marginal 5.4% benefit in survival with recurrence approaching 50% of all operable cases, to perioperative chemoimmunotherapy as a transformative strategy. Five randomized trials have evaluated chemotherapy plus nivolumab, pembrolizumab, durvalumab, or toripalimab, either as neoadjuvant or perioperative (neoadjuvant plus adjuvant) therapy, with all five trials showing significant improvements in the rate of pathologic complete response (pCR) and event-free survival (EFS). Perioperative strategies with 3-4 cycles of neoadjuvant chemoimmunotherapy and 1 year of adjuvant programmed cell death (ligand) 1 [PD-(L)1] blockade combine the efficacy of purely adjuvant [effective for both stage II and stage III tumors with event-free survival hazard ratios (HR) of approximately 0.70] and the purely neoadjuvant strategies (effective only for stage III with a lower EFS HR of approximately 0.50), show benefit across the entire spectrum of PD-L1 tumor expression levels, and significantly improve overall survival, as the NADIM-2 and Keynote-671 studies recently showed. Randomized phase III trials have shown efficacy of neoadjuvant nivolumab, perioperative pembrolizumab, adjuvant atezolizumab, and adjuvant pembrolizumab with improvement of event-free/disease-free survival of 24% to 42%, while three additional phase III trials reported pathologic complete response rates of 17% to 25%, significantly better than chemotherapy alone. KEYNOTE-671 demonstrated a significant OS advantage, while AEGEAN and CheckMate 77T showed consistent EFS improvements, with OS data still maturing.

For stage III disease, immune checkpoint inhibitor (ICI) therapy has become a standard recommendation in curative intent therapy. For patients with resectable NSCLC, two trials have demonstrated that adjuvant atezolizumab or pembrolizumab, following chemotherapy, significantly improved disease-free survival (DFS), generally administered for 1 year after postoperative chemotherapy, but only atezolizumab for patients with tumor programmed death-ligand 1 (PD-L1) levels of 50% has demonstrated a benefit in OS. Neoadjuvant chemotherapy with nivolumab offers a strong EFS benefit for patients with resectable stage IB to IIIA NSCLC, and neoadjuvant and perioperative chemoimmunotherapy has transformed the treatment of tumors >4 cm or node-positive disease (stage II to IIIA, AJCC 8th edition). For unresectable stage III NSCLC, one year of consolidation durvalumab following concurrent chemoradiation has demonstrated significant improvements in both progression-free and overall survival, and in 2017 the PACIFIC Trial demonstrated that the addition of consolidative immune checkpoint inhibitor durvalumab for 1 year led to superior progression-free survival (PFS) and 3-year overall survival compared to placebo in patients who achieved disease control with concurrent chemo-RT. In parallel, targeted adjuvant therapy has reshaped management of oncogene-driven early disease: in patients with tumours harbouring a common mutation of the EGFR gene, adjuvant osimertinib therapy was associated with a large improvement in both DFS and overall survival (OS), with treatment with adjuvant osimertinib for 3 years associated with significant improvement in both DFS and OS in patients with stage IB-IIIA, resected EGFR exon 19 deletion, or L858R-mutated NSCLC. Adjuvant osimertinib in EGFR-mutated NSCLC and adjuvant alectinib in ALK-rearranged NSCLC have both received regulatory approvals, with US Food and Drug Administration approval of osimertinib and alectinib as adjuvant treatments for resected pathologic stage II/III EGFR and ALK-mutated NSCLC.

In oncogenic-addictive metastatic NSCLC, primarily in adenocarcinoma, the range of targeted therapies is expanding, with expected overall survival measured in years. By 2021, the FDA and EMA have approved targeted agents to inhibit EGFR activating mutations, T790 M resistance mutation, BRAF V600E mutation, ALK, ROS1, NTRK and RET fusion. In 2022, the range of authorized target therapies was expanded with therapies that inhibit KRASG12C, EGFR exon 20, HER2 and MET. Until now, there was no registered targeted therapy for the KRAS mutations, which affect 30% of adenocarcinomas, with the greatest expectation surrounding inhibition of the KRAS G12C mutation, which occurs in ∼15% of NSCLC, mainly in smokers and is characterized by a poor prognosis. Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy, while adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1. In EGFR exon 20 insertion mutation of lung adenocarcinoma, amivantanab was registered for progression after platinum-based chemotherapy, while lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%.

Aumolertinib's Expanding Clinical Development Beyond NSCLC

Beyond non-small cell lung cancer, aumolertinib (almonertinib) has been explored in colorectal cancer models and in recurrent glioblastoma harboring an EGFR p.L858R mutation. Available data are limited to preclinical xenograft work and a single-patient case report rather than prospective controlled trials.