2014/10/29 Pipeline Innovation will Expand NSCLC Treatment Algorithm

Written By Joshua Libberton, GBI Research's Associate Analyst

Non-Small Cell Lung Cancer (NSCLC) is the biggest cause of cancer-related death worldwide, with an average five-year survival rate of just 14%. Survival rates vary substantially according to whether a patient is diagnosed with early-stage NSCLC or late-stage NSCLC. Unfortunately, low-key symptoms and expensive or inefficient diagnosis techniques mean that 70% of patients are diagnosed in stage IIIB/IV, which is the main reason for the poor survival rate.

There are three main histological subtypes of the disease: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Adenocarcinoma and large cell carcinoma are frequently grouped together into a non-squamous category. Histological diagnosis is crucial to determining the best course of treatment; however, a gradual shift towards diagnosis based on the molecular characterization of tumors is increasingly evident. With the emergence of targeted therapies such as the EGFR inhibitor, Tarceva (erlotinib) and the ALK inhibitor, Xalkori (crizotinib), patients with specific molecular aberrations can be treated with premium therapy, which adds a greater level of precision to treatment.

One of the major issues in the NSCLC market is that the rate of discovery of driver mutations within tumors is far outpacing drug development, leading to an incredibly segmented market with a severe lack of targeted therapies for each NSCLC subpopulation. Currently, only EGFR and ALK-positive patients can be treated with targeted therapies, yet mutations in genes such as c-MET, FGFR and PI3KCA have been identified in significant portions of the NSCLC population. Therefore, histology-based treatment will remain crucial for the time being. However, as more targeted therapies proliferate onto the market, treatment will be more based on a tumor’s defining molecular features rather than histology alone.

Targeting niche market segments can generate significant revenues, with Alimta generating $2.7 billion in 2013 from non-squamous patients and Tarceva generating $1.3 billion primarily from EGFR-positive patients. This indicates a clear commercial and clinical rationale for pursuing targeted drug development, with significant benefits to the outlook for patients and potentially high revenues for developers.

Our Frontier Pharma analysis at GBI Research has revolved specifically around first-in-class innovation in the NSCLC market. We found that in aiming to address the need for more targeted therapies and to exploit the multiple niches that have emerged through the molecular profiling of NSCLC tumors, the industry has placed a huge focus on developing first-in-class products. Compared to the market, the diversity of molecular targets is remarkable, with many crucial oncogenic processes being targeted, rather than spindle formation or DNA repair as is the case with the vast majority of marketed chemotherapies. Further still, 38% of the 389 pipeline products have a first-in-class target. These products cover a vast range of targets in an array of cellular processes, such as cyclin-dependent kinases in cell cycle progression to FGF1 in growth factor signaling. By adopting this targeted approach, specific cancer processes can be modulated, thereby reducing the number of target effects to healthy cells.

However, while the initial signs are promising in terms of first-in-class development revolutionizing NSCLC treatment, in-depth analysis has revealed substantial differences in the promise that these targets show in NSCLC treatment. Some first-in-class targets were aligned to integral NSCLC signaling pathways, such as PI3K or Ras, whereas others lack this alignment, raising questions about their efficacy and their specificity to cancer cells. Of the aligned targets, many have a strong supporting rationale in literature, as well as favorable results in preclinical trials. Notable examples include Aurora kinase B and Akt2.

In examining the NSCLC deals landscape, we found very few deals completed for NSCLC products, especially those with a first-in-class target. However, examining licensing deals for first-in-class products in detail indicated a skew towards first-in-class deals being made earlier in development than their non-first-in-class counterparts. This trend was supported by industry-wide data, suggesting that pharmaceutical companies are keen to expand their first-in-class developmental portfolio to a degree where they will accept more risk by licensing an early-stage therapeutic for its first-in-class status.

Overall, the future market outlook for NSCLC is very promising. GBI Research’s previous Therapy Analysis report: “Non-Small Cell Lung Cancer Market to 2020 - New Therapies to Enhance Treatment Segmentation and Drive Growth in an Increasingly Competitive Market” reported a significant increase in market value over the next few years. It also revealed a healthy pipeline with vast numbers of innovative approaches to NSCLC treatment, indicating promising signs for the market and treatment algorithm in the long-term future. Broad-acting chemotherapy has played a huge role in oncology; however, first-in-class approaches look to create a more personalized, tumor-specific course of treatment. Although, with combination therapies rapidly becoming the norm, it is highly likely that these chemotherapies will play a significant role in NSCLC treatment by combining with first-in-class targeted therapies. With an array of promising and innovative treatments in the pipeline, as well as a molecular based classification of tumors becoming more important, the NSCLC landscape appears to be undergoing some very exciting changes.


Source: GBI RESEARCH