An Examination of Patient Data in Japan
The transformation of treatment paradigms in oncology continues unabated as the last two decades saw an extraordinary diversification of product technologies and improved both efficacy and outcomes for patients suffering from a range of indications. The number of ongoing clinical trials and emerging technologies in the R&D pipeline will continue to drive successful innovation. What is less clear, however, is how new therapeutics are used in the clinic and what impact they are having.
Whilst clinician surveys consistently report that the average patient dosing compliance is around 80% of the recommended dose, according to a product’s label, this is not supported by the data.
Recent research conducted by Decision Resources Group in Japan indicates that more than 57% of patients with multiple myeloma receive less than 70% of the of recommended oral dose (in mg) in the first treatment cycle, according to the product label, in first-line therapy for Revlimid, a long-established pillar of multiple myeloma treatment. This is consistent with minor variations across the first eight cycles of therapy in the patient cohort we analysed. In second line therapy, between 60% and 62% of patients receive less than 70% of the recommend dose per cycle. Whilst the Electronic Medical Records (EMR) data we utilized does not provide details on the injected dose of a drug per injection, our analysis of the injection frequency per cycle shows that between 41% and 53% of patients do not receive the recommended three injections per cycle of Velcade in transplant-ineligible second-line treatment setting between cycles one and eight. Assuming that clinicians are unlikely to over-compensate a missed injection with a higher subsequent dose, it is very likely that, again, patients are significantly under-dosed. Time and again, our analysis demonstrated very consistent patterns across a range of both oral and intravenous products including Pomalyst, Ninlaro, Farydak, Kyprolis and others.
The low dosing compliance could be due to a spectrum of clinical factors as these patients are generally in poor health and, consequently, toxicity and tolerability are likely factors that cause clinicians to be more cautious in the treatment approach. However, both the extent as well as the magnitude of low dosing is surprising as, ultimately, a consistently low dose may lead to poorer outcomes.
In addition to the low dosing compliance, our research also shows low temporal compliance with the recommended treatment regimes according to their label as the onset of subsequent cycles of treatment is often significantly delayed. For example, an assessment of the time lag in product dispensations showed that only 47% of patients were dispensed Pomalyst pills prior to or just in time to initiate cycle two or their treatment in the transplant-ineligible second line therapy. In 45% of patients, the delay was seven days or more from the completion of cycle one until they were dispensed product ready for the onset of cycle two. These delays gradually worsen across the patient population as, by the end of cycle eight, only 22% of patients are dispensed Pomalyst prior to or on time for the onset of cycle nine. Conversely, 74% receive their refill seven days or more later than they should.
These results raise serious clinical questions about the effect of low dosing compliance and delays in product dispensation in the treatment of oncology indications and require further investigation. However, they are also vitally important for biopharma companies as, both the extent and magnitude of these observations may result in poorer health outcomes in patients that would not be a true reflection of a product’s efficacy and safety profile. Over time, it has the potential to lead to a weaker product perception by clinicians and lower drug utilization, market share and commercial potential of a drug.
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