Frontier Pharma: Innovative Licensing Opportunities in Non-Hodgkin Lymphoma
Non-Hodgkin Lymphoma (NHL) can be seen as a collection of up to 60 smaller subtypes of malignant lymphoid disease, defined by distinct morphological, cytogenetic and immunophenotypic characteristics that can be broadly classified as either indolent or aggressive disease. The slow growing nature of the former means that first-line treatment for diagnosed patients can be delayed, an option not commonly recommended for aggressive disease. Across both indolent and aggressive disease, first-line chemotherapy in combination with the blockbuster drug rituxumab can induce high rates of response, and prolonged durations of remission. Despite this, indolent disease is typically incurable, with the most aggressive lymphoma subtype - diffuse large B-cell lymphoma having 5-year survival rates of ~50%. Re-treatment with chemotherapy can induce second and subsequent remissions, but most NHL patients develop chemotherapy resistant disease, for whom there are limited treatment options. Overall, in terms of numbers small molecule chemotherapeutic agents dominate the current market, with a clear need for novel targeted therapies to prolong durations of remission, and provide options for patients with chemo resistant, heavily pretreated disease.
The current developmental pipeline addresses these gaps in the market, dominated by cancer immunotherapies and inhibitors of cancer-associated signal transduction. Pathways of significant interest include B-cell receptor signaling, the PI3K/Akt/mTOR pathway, and Wnt/ß-catenin signaling, as well as oncogenes such as BCL-6 and BCL-2. Characteristic cell surface molecules that represent targets for cancer immunotherapies include CD19, LMP-1/2 and CD20, with several pipeline drugs already approved for CD20. First-in-class drug development in NHL corresponds strongly to these known somatic mutations and affected pathways. Clinical results of drugs against profiled targets in this report show many are being investigated in relapsed disease.
There are 666 marketed products for NHL, 95% of which are small molecules -
Non-Hodgkin Lymphoma Treatment Pipeline Shows Below Average Innovation, says GBI Research
The product pipeline for Non-Hodgkin Lymphoma (NHL) exhibits a lower degree of innovation than both the industry and oncology average, with just 28% of all pipeline products, or 33% of the pipeline for which there is a disclosed molecular target, categorized as first-in-class. This is in comparison to industry, breast cancer and lung cancer innovation rates of 43%, 57% and 59%, respectively, says business intelligence provider GBI Research.
The company’s latest report* states that while NHL, collectively, is the sixth to tenth most common cancer dependent on territory, each individual subtype is classified as an orphan disease. With significant differences in each subtype’s genetic profile and current treatment, there is reduced scope for the development of a targeted therapy with cross-subtype activity.
This does not present NHL drug development as an attractive investment in comparison to other indications in oncology, particularly as survival durations across many NHL subtypes are relatively strong, and likely the reason for low first-in-class innovation levels.
However, Katie Noon, Senior Analyst for GBI Research says that innovation is present to varying degrees across the majority of molecular target families and development stages for NHL therapeutics, rather than localized to a particular subset of therapies.
Noon says: “There is a considerable range of clinical potential across treatments with first-in-class status, particularly those restricted to the early-stage NHL pipeline. Some targets, such as spleen tyrosine kinase, boast plenty of supporting scientific and clinical evidence, while others have shown mixed results in Preclinical studies and lack clarity on their role in disease pathophysiology.”
GBI Research’s report also notes that despite the difficulty of several targeted NHL therapies in achieving improved efficacy rates, the development of such treatments remains of key interest across NHL.
Noon continues: “It is hoped that one of these many targeted therapy pipeline products will replicate the success observed with rituximab, which significantly altered the NHL treatment landscape following its approval.
“Clear gaps in the treatment algorithm include maintenance therapies to prolong initial or subsequent durations of remission, and improved therapies for relapsed patients, particularly those with a second or subsequent relapse,” the analyst concludes.
*Frontier Pharma: Innovative Licensing Opportunities in Non-Hodgkin Lymphoma
This report provides analysis of the Non-Hodgkin Lymphoma (NHL) treatment pipeline, stratified by stage of development, molecule type and molecular target. It includes information on the current clinical and commercial landscape, and the composition of the NHL therapeutics market in terms of dominant molecule types and targets, as well as highlighting current unmet needs.
This report was built using data and information sourced from proprietary databases, primary and secondary research, and in-house analysis conducted by GBI Research’s team of industry experts.