Oncology drug development is one of the largest areas within the pharmaceutical industry, addressing a disease area that causes more deaths than all other diseases apart from cardiovascular. The current global oncology market is estimated to be in the region of $55bn and forecast to grow to over $70bn by 2016. The oncology market is often seen as the most diverse with a wide range of indications and there are some 900 estimated clinical programmes currently underway. It is estimated that there are more than 200 different forms of cancer and therefore the oncology market presents a unique set of challenges to the industry.
This unique challenge has led to the development of a number of different business models. Different companies are seeking to address different areas of the cancer market, with some preferring rare cancers with products categorised under the orphan drugs regulations, while other companies look for the next cancer blockbuster like Rituximab. The oncology market has seen an incredible amount of change over recent years this trend is set to continue throughout 2012 and beyond as the healthcare costs continue to dominate domestic level politics and patients become increasingly better informed of their treatment options. Below, Liftstream has analysed our top 5 trends in the oncology drug development market for the coming years.
1. Personalised medicine is here to stay:
Personalised medicine is a term that is not solely assigned to cancer, even though it is frequently used in this context. Cancer and personalised medicines have always been closely linked; for example the identification of certain breast cancer genes (BRCA) allows doctors to advise patients whether they have an increased chance of developing cancer. Many leading doctors and academics believe that the future of cancer treatment lies in the development of personalised medicine. Many drugs now are being launched with companion diagnostics in order to identify patients that will respond to drug treatments and reduce adverse events. Roche, a company who spend 50% of their R&D budget on drug development in oncology, have made big bets on companion diagnostics. Severin Schwan, CEO of Roche recently said “More than 60% of our pharmaceutical pipeline projects are coupled with development of companion diagnostics in order to make treatments more effective”. Both Perjeta and Zelboraf are examples of personalised medicine becoming reality. Companion diagnostics still face significant challenges from a pricing and reimbursement despite their obvious efficiency in treating patients. Where diagnostics tests offer definite yes/no outcomes about treatment their reimbursement is more straightforward, however, it is not always clear-cut. They do have the capability to save reimbursement entities considerable savings, hence the growing swell of interest.
Patient selection with biomarkers will also play an increasingly important role in the clinical development of drugs. By excluding the non-responders in clinical trials, increases in efficacy will become more apparent and thus ease regulatory approval. Cancer Research UK, partnered with AstraZeneca and Pfizer, are currently conducting a pilot study to demonstrate on a small scale how the NHS can provide molecular diagnosis for all cancer types routinely. The results of this study are due in July 2013.
2. Antibody conjugates are beginning to show promise:
The concept of Antibody-drug conjugates is to take a ‘naked’ antibody link it to a toxin and design in combination so it unleashes the toxin on the tumors. Done right, the drug will have more punch than traditional ‘naked’ antibodies. Most previous attempts at this class of drug have shown mixed results. Recently however, Seattle Genetics and Genentech/Roche have shown promising results. Seattle Genetics’ Adcetris was approved last year for lymphoma and Genentech’s (now Roche) T-DM1 is in late stage trials for breast cancer. T-DM1 is an investigational ADC that attaches trastuzumab to the chemotherapy agent DM1 via a stable linker. It is designed to target and inhibit HER2 signalling and deliver the chemotherapy directly inside HER2-positive cancer cells. Both drugs have shown they can be powerful drugs for cancer patients. This promising set of results has led to a wave of interest in the pharma and biotech industries. This promising field is highlighted by Genentech’s commitment with T-DM1 being just 1 of 25 different Antibody-drug Conjugates in various stages of development.
3. Move from PFS to OS outcome measures:
A developing trend within clinical phase studies is the shift from progression-free survival (PFS) to overall survival (OS) as an endpoint. The shift from PFS to OS first hit the headlines when the FDA granted accelerated approval for Genentech/Roche’s Avastin (bevacizumab) in combination with Taxol (paclitaxel) to treat metastatic breast cancer. Approval by the FDA was granted solely on the basis of improvements in PFS and was not also replicated by OS. OS was used as a secondary endpoint and the results were far less impressive than they were for the PFS results. The FDA defended the approval by stating it had approved 3 other breast cancer drugs via PFS. However patient advocacy group National Breast Cancer Coalition Fund stating that the regulatory bar for Avastin in mBC had been lowered.
The difference between PFS and OS is that PFS measures the time from a patient’s random assignment to one treatment arm until the patient’s cancer begins to grow again or the patient dies, whereas OS measures time from randomisation to death from any cause. Central to the argument in using PFS as an endpoint; does delaying disease progression matter if a cancer treatment doesn’t lengthen a patient’s life? The FDA considers OS to be the more reliable endpoint for clinical trials with cancer drugs. However demonstrating that an experimental drug improves OS is no easy feat. The trials require hundreds of patients that can take years to complete. Trials that use PFS solely as an endpoint can be completed much quicker than those using OS therefore appeal to pharmaceutical companies.
4. Shift from viewing cancer as a curable disease to a chronic disease:
The shift from viewing cancer as a curable disease to a chronic disease is one that has established a swath of support and investment within the industry. While many patients still look for the ‘one pill cure’ doctors, pharmaceutical industry professionals are beginning to work towards cancer being a chronic, manageable disease. As a result, companies are re-aligning their research efforts into redefining all types of cancer. Rather than the preferred current regime of potentially fatal cytotoxic therapies, genetic profiling improves clinician’s ability to detect patients who could benefit from long term therapy, which will hopefully lead to increased survival rates and higher quality of life for patients. Within the pharmaceutical and biotechnology community there are many examples of companies pursuing this strategy. For example, within big pharma AstraZeneca has made no secret of its pursuit of this oncology disease approach. While in the biotech space, Blueprint Medicines, the US biotechnology company, started with a view to treating cancer solely as a chronic disease. With industry heavyweights like Mark Levin’s Third Rock Ventures backing Blueprint Medicines, it seems that researchers and the venture capital industry alike are seeing the benefits of treating cancer as a chronic disease.
5. More innovative trial designs are needed to demonstrate quality of new drugs:
Two recently completed clinical studies have highlighted the need for more innovative trial design in order to fulfil the ever tougher regulatory requirements. Firstly a study demonstrated the value of evaluating not only efficacy but patient tolerability too. The second study stands out because the results show that the drugs don’t take away from patient’s quality of life which is practically unheard of with most cancer treatments.
However the most significant area of development in trial design are Adaptive Clinical Trials. Adaptive trials are designed to use accumulating information to determine how to modify the trial as it progresses. The adaptive parts of the trial are predetermined before the trial starts. Any modifications must maintain the validity and integrity of the trial. Adaptive trial design is gaining traction in the oncology field for a number of reasons mainly: greater demand for efficacy in trials, many new targeted therapies will only demonstrate efficacy in particular subset of patients and patient advocates have been pushing adaptive trials for a number of years.
Oncology is an area of significant focus for the industry and continues to dominate global drug development pipelines. In the 2012 Ernst and Young – Beyond Borders Biotechnology report, a projected 32% of all phase III trials in the USA are in oncology, with Europe at 29% of trials. In 2011, the FDA approved 35 new drugs, 10 of which were approved for oncology and this in spite of what is seen as an increasingly difficult regulatory environment. In fact, in a further report produced by the Tufts Center for the Study of Drug Development, oncology drugs achieved approval times by the FDA which were 10 months shorter than non-oncological products from 2002 through 2011, accounting for 19% of approvals during that period. Although in Europe the opposite was true by a factor of 2 months.
The industry is looking to new innovations, better diagnostics, improved understanding at the genetic and molecular level as well as improved data to drive the efficiency of development. All of which should provide new insights into novel targeted therapies. Equally, industry is rethinking its approach to the way it treats patients and the future of this complex disease. For now, cancer remains a market of high commercial promise and with such disease prevalence among populations, a considerable healthcare issue. Let’s hope some of the current trends begin to deliver the outcomes that industry and patients long for.