Drug development in oncology is an attractive prospect; many oncology indications are characterized by growing incident populations, have large unmet need, and support high drug prices. However, securing a foothold in these competitive markets can be tricky, with many companies failing to clear the high hurdle of demonstrating positive clinical data to support approval, while others struggle with market access barriers and other factors affecting physician prescribing post-approval.
The early-Phase pipeline for oncology is large, dynamic, and diverse. For breast cancer alone, approximately 150 drugs are in active Phase I and II development. While the turnover of drugs in this setting is high (many never reach late-Phase trials), this is also an area of opportunity for companies seeking to either out-license their assets or acquire promising novel agents. Currently, many marketed or late-Phase oncology drugs are not developed solely in-house, having passed through various licensing and acquisition deals during their development, highlighting the important role of these deals in getting effective drugs to market. Partnering and collaboration between companies is also increasingly important; for example in the whirlwind of drug development surrounding the immune checkpoint inhibitors in oncology, a steady stream of partnering and collaboration deals continue to materialize as companies seek to investigate their agents in novel combinations.
Many companies are drawn develop therapies for lucrative high incidence markets such as breast cancer and NSCLC, however markets like these are often packed with currently approved therapies which set a high bar for approval. Lower incidence indications typically have less competition, however in these markets companies must secure high patient shares and/or premium-prices with long treatment durations to garner substantial drug sales. Commercial success in smaller oncology markets is still possible as demonstrated by AbbVie/Johnson&Johnson’s Imbruvica for previously treated MCL and relapsed/refractory CLL, its sales having reached over $1.5 billion within three years. Smaller populations, whether entire indications (such as CLL) or subpopulations of indications (for example, ALK-translocation-positive NSCLC) may be granted orphan status by regulatory authorities, which gives companies incentives such as longer market exclusivity, tax credits, fee reductions, and support during the drug approval process in these markets. Targeting subpopulations using a biomarker in high incidence indications is an effective strategy, for example, while only approximately 6% of NSCLC patients are eligible for ALK inhibitors, sales for this drug class are set to break through $1 billion before 20201. Using a biomarker is an attractive strategy because it carves out populations most likely to respond to a drug (typically yielding better clinical data), is viewed favorably by HTA bodies (particularly those in Europe), and is well received by prescribing oncologists. As well as isolating niche populations, biomarkers can identify large patient subsets. For example, approximately one fifth of breast cancer patients are HER2-positive2, yielding worldwide sales of HER2-targeted agents in 2015 of over $9 billion, fueled by high rates of HER2 testing, deep penetration in the breast cancer treatment algorithm, long treatment durations, and premium pricing. Development of biomarkers in oncology is a key area where company collaboration and partnering is playing a pivotal role. For example, the development of PARP inhibitors for BRCA1/2-mutation-positive ovarian cancer has seen AstraZeneca and Medivation (since acquired by Pfizer) separately collaborate with Myriad Genetics’s for their BRCA1/2-mutation testing capabilities, and has also seen Clovis Oncology collaborate with Foundation Medicine to develop a companion diagnostic for their PARP inhibitor. Biomarker-driven therapies are not always a home-run though – for example despite Tokai Pharmaceutical’s galeterone being developed for AR-V7 expressing prostate cancer, this drug’s Phase III trial was terminated after a recommendation from its independent data monitoring committee that it was unlikely to meet its primary endpoint.
While positioning a drug in an appropriate population is key, there are many other factors at play in the success of a drug. Clinical trial design is central, and as part of this companies must make careful choices to select the most appropriate comparator therapy and trial endpoints. While overall survival, the gold standard efficacy measure for a drug is the most highly desirable endpoint in any oncology clinical trial, significant improvements of other measures that vary by indication can also result in dramatic changes to clinical practice. For example, in diseases such as SCCHN and glioma that are characterized by poor patient quality of life, drugs that provide improved toxicity and/or improved quality of life still have the potential to receive healthy uptake, even if their efficacy data do not substantially outshine other available treatments. The choice of an appropriate comparator in a clinical trial is also key. While it is tempting to select an underperforming comparator to facilitate the collection of better relative data, this can have ramifications during pricing and reimbursement negotiations. Clinical trial comparators are increasingly scrutinized by HTA bodies, for example, Germany’s G-BA concluded that the comparator used in the Phase III trial for Novartis’s Tafinlar for BRAF-mutation-positive malignant melanoma was inappropriate, and instead, compared it to another agent, the outcome of which lead the agency to conclude there was no added benefit proven by Tafinlar.
Drug development in oncology is complex and diverse, with many twists and turns in the road to approval. Decision Resources Group’s syndicated offerings and tailored consulting provides companies of all sizes with insights into a diverse range of topics in this field, covering key themes that will be discussed at this year’s BioEurope partnering conference in Cologne, Germany, including market access and drug development. If you’d like to find out more about the services Decision Resources Group can offer, come visit us at Hall 7, Booth 38.
Insights in this article are drawn from various Decision Resources Group offerings. More detailed information is available through our Company and Drug analysis, Epidemiology, Disease Landscape & Forecast content, and our Access & Reimbursement research.