Oncology R&D investment has been consistently increasing. A case in point: Of the 65000 trials registered on clinicatrials.gov, there are approx. 19000 product related ongoing trials. It´s noteworthy that a trial´s probability of success hasn´t increased over the years i.e. most of these trials face a higher risk of failure than ever before.
A few highlights from 2018:
- 15 new drugs launched for 17 indications
- Currently >700 companies are undertaking clinical development activities; of these 463 are being sponsored by companies with <$200 M R&D spends
- There are 849 New Molecular Entities (NMEs) in late stage development
- There are 450 Immunotherapies and 98 next gen biotherapeutics (including cell, gene and nucleotide therapies) under clinical investigation
Challenges abound but there are ways to work through them
Oncology Clinical Development remains high-risk undertaking with the composite success rate falling to 8.0% in 2018 (11.7% in 2017). Let’s look at the minefields below:
- Rapidly changing SoC: As new treatments enter the market; the guidelines change rapidly. The trial sponsors need to design their protocols with a high degree of adaptability. Adaptive trial designs can account for uncertainties in future standard of care
- Patient Enrolment: Given the booming pipeline, the high Diagnosis/Treatment rates leading to rapidly diminishing pool of treatment naïve patients and, increasingly stringent patient selection criteria, it is getting increasingly difficult to enroll patients for clinical trials; <3%-5% of patients actually get enrolled in clinical trials upon diagnosis.
- Tumor heterogeneity and resistance: The intra-tumoral heterogeneity makes it difficult for our immune system to launch an effective attack. This heterogeneity also instigates resistance to any single-targeted cancer treatment. Greg Hannon of Cancer Research UK has recently got £20 M grant to create virtual reality maps of tumors. Such maps will inform the combination approaches that are most suitable to prevent tumor progression and metastasis.
- Tension Between Science and Business: Other than large/medium pharma, most companies do not have the luxury of sequentially implementing their lifecycle management plan. Basket or Umbrella trials are large sized studies across multiple tumors. These trials enable an organization to explore their molecules´ relevance in multiple tumors and make an informed decision on which tumor types to continue studying in more advanced and expensive studies
- Trial Duration: Given the increasing criticality of speed-to-market, trial duration matters! Oncology trials duration has decreased over the last few years, but is still high (P1: 7 months; P2: 11 months; P3: ~1year)
- Clinical Trial Monitoring Talent: Clinical research associates need highly specialized skills in oncology and in the specific tumor subtype being studied in a trial. Referrals, Networks, Oncology Communities (based at charities, hospitals, or research institutions, universities) can be very useful in identifying individuals with the right mix of specialist skills and patient/site management.
Where´s the holy grail?
The 2024 Oncology Prescription Drug market is forecasted at north of $250 B and clinical development spends will reach ~$91B during the same time. Despite the challenges, the competitive intensity shows no sign of abating. Is it rational? Is it the hope of outsized rewards or plain greed? Who´s to say..