European Medicines Agency Approves the Treatment Found Most Effective for Small Cell Lung Cancer

On September 19, 2024, the European Medicines Agency (EMA) issued a positive opinion recommending marketing authorization in European Union countries to treat extensive-stage small cell lung cancer with Hetronifly, containing serplulimab (Henlius Europe), an immunotherapy medicine.

Small cell lung cancer (SCLC) generally requires aggressive treatment because it grows rapidly and spreads early, and it accounts for approximately 15% of all lung cancers. This cancer is more common among smokers and has usually metastasized by the time it is diagnosed, presenting at an extensive stage. Chemotherapy was considered the most effective standard treatment for many years. In recent years, however, adding immunotherapy to these treatments has substantially improved survival rates.

In this context, one treatment option that has attracted attention following recent developments is the immunotherapy agent serplulimab. Serplulimab, developed by Henlius, a biotechnology company originating in China that also operates in Europe, is an anti-PD-1 antibody first approved in China. On September 19, the European Medicines Agency (EMA) recommended that serplulimab also receive marketing authorization in Europe. In this article, we discuss serplulimab's effects on survival outcomes in the treatment of advanced small cell lung cancer and examine findings from ASTRUM-005.

ASTRUM-005: The Longest Survival Outcomes With Serplulimab

ASTRUM-005 is a phase III clinical trial examining the effectiveness of adding serplulimab to chemotherapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The study evaluated serplulimab's effects on overall survival and progression-free survival.

Among the 585 patients enrolled in the trial, survival outcomes improved markedly in the serplulimab group:

• Median overall survival was reported as 15.4 months in the serplulimab plus chemotherapy group, compared with 10.9 months in the placebo group. These data indicate that treated patients lived approximately 5 months longer (HR: 0.63).
• Median progression-free survival was 5.7 months in patients treated with serplulimab, compared with 4.3 months in the placebo group (HR: 0.48).

These results show that serplulimab is highly effective in treating ES-SCLC and significantly prolongs survival compared with existing treatment options.

Below is an indirect comparison of the results of 3 notable studies in first-line treatment of ES-SCLC. 

Side Effects and Safety Profile

Immune-related effects, such as hypothyroidism and hyperthyroidism, were more common among the side effects of serplulimab treatment. Serious (grade ≥ 3) side effects were reported in 33.2% of the serplulimab group and 27.6% of the control group. Overall, the treatment demonstrated a safe profile when used with chemotherapy.

EMA's Recommendation for Hetronifly: The Start of a New Era

EMA's recommendation for serplulimab (Hetronifly) is considered a major step toward making this treatment available in Europe. The European Medicines Agency presented strong evidence that serplulimab significantly increases survival and treatment response when used in combination with chemotherapy. This offers new hope, particularly for patients with advanced small cell lung cancer.

Conclusion: A New Standard in Small Cell Lung Cancer Treatment

Immunotherapy is becoming increasingly important in the treatment of advanced small cell lung cancer. Serplulimab has taken its place among the treatments providing the best survival outcomes in this disease. If full FDA and EMA approvals are obtained, serplulimab will become one of the standard treatment options worldwide. This development has the potential to make a major difference, particularly in long-term survival.

Differences Between FDA and EMA Approvals

Approvals from the FDA (United States Food and Drug Administration) and EMA (European Medicines Agency) are regulatory approvals granted to demonstrate that medical products, medicines and medical devices meet safety, efficacy and quality standards. However, the two agencies differ in their approval processes, jurisdictions and assessment criteria.

How FDA and EMA Approvals Differ:

1. Jurisdiction:

   • FDA: It has regulatory authority over medicines, biological products, medical devices and food in the United States. FDA approval is required for a product to be marketed in the United States.
   • EMA: It oversees the safety and efficacy of medicines in European Union (EU) countries. EMA approval is required for a product to be marketed in EU countries.

2. Assessment Process:

   • FDA: Its assessment process is generally more centralized and conducted directly by the FDA. Extensive phase III clinical trials usually need to be completed before a product is marketed in the United States. The FDA reviews the application directly, generally through a lengthy and detailed process.
   • EMA: EMA assesses medicines through independent experts and committees in EU member states. EMA approval provides a "centralized marketing authorization" valid throughout the EU and implemented in its member states. The process operates more as a community-based assessment.

3. Scope:

   • FDA: The FDA makes decisions only for products in the United States.
   • EMA: EMA's decisions apply throughout the EU and cover many European countries.

Can a Medicine Receive EMA Approval Without FDA Approval?

Yes, EMA approval can be obtained without FDA approval. Each regulator's approval process for a medicine or medical product depends on its own criteria and timeline. For example, an application may be submitted earlier in Europe and approved there first, while approval in the United States may come later. This means a medicine may be marketed in one region while still awaiting approval in another.

What EMA Approval Means:

• EMA approval means that a medicine can be marketed in European Union and European Economic Area countries. The product can therefore enter the European market and be used there.
• Receiving EMA approval without FDA approval means the medicine or treatment has been found safe and effective in countries outside the United States, but additional approval is needed before it can be marketed in the United States.

This process shows that regulatory differences may exist between countries or regions, and that approval of a medicine in one place does not necessarily mean it has been approved elsewhere. For example, EMA approval of serplulimab indicates that it has been found safe and effective for use in Europe, but it cannot enter the United States market without FDA approval.

Ultimately, this can lead to differences in access to the global market. Because FDA and EMA approval processes are independent, however, applications for a medicine can be submitted to both agencies and approval can be obtained from each.