The late lifecycle of a branded pharmaceutical is a time of great activity … the original primary indication may have been complemented with additional indications for use resulting in a potentially large population who may be eligible for treatment, with the consequent health benefits for users in addition to commercial success at brand and corporate levels.
Yet this time of delivering “value” in the form of improved patient health and revenue to fuel future R&D investment and investor returns may be tinged with an element of sadness … how much longer will the high-performing brand team remain intact, who may be selected (or jump) to the excitement and promise of a soon-to-launch brand, and who will remain at-the-helm to steer the brand’s transition through loss of exclusivity (LoE) and the arrival of generic/biosimilar competition? In the midst of this change remains a critical scientific, medical and corporate priority, namely ensuring “the safe and appropriate use” of the product by informed patients and prescribers.
In this brief article we shall describe the multiple distinct and complementary activities that encompass “safe and appropriate use” for a late lifecycle product – a remit that is usually driven by the Medical Affairs (MA) team.
Within a commercial biopharma setting, MA is a sophisticated, multi-disciplinary capability comprising physicians, pharmacists and allied health professions, and population health and biomedical scientists dedicated to biopharmaceutical innovation.
The MA team is recognized to lead efforts to support the safe and appropriate use of prescription drugs. This extends to a variety of activities:
- Prescriber education including writing evidence-based responses to specific questions from prescribers.
- Contribution to the development and oversight of Ph IIIb/IV trials.
- The identification, commissioning and pull-through of independent research designed to explore and advance product use through Investigator Initiated Research
- Thought Leader engagement at local, regional and national level.
- Compassionate access for patients with limited options and for whom the product may not be indicated, but where scientific rationale exists.
“Late lifecycle” has many definitions – given the average branded life of 10 years and the common phases of “Launch” (years 1+2) and “Mid-Lifecycle” (years 3-7), we focus on the later years (8-through LoE and beyond). We identify multiple, important contributions from MA during this phase:
- Continuing to inform safe and appropriate use.
- For example, emerging alternative treatment options will raise questions about switching and the relative effectiveness of different treatment sequences. And MA has the capability to deliver this service through the existing, educated and dedicated field medical team that has contacts within the prescriber community.
- Through continued evidence generation and dissemination, Medical Affairs should continue to inform on real world outcomes, potentially asking and answering questions on clinical outcomes where data on sequencing of therapies in clinical practice exist.
- Identify sub populations for whom the benefit:risk profile is especially positive.
- For example, as prescribers become familiar with the real-world benefit:risk profile the drug may emerge as an ideal option for specific people such as the elderly, low/high BMI, or highly comorbid.
- For example, as prescribers become familiar with the real-world benefit:risk profile the drug may emerge as an ideal option for specific people such as the elderly, low/high BMI, or highly comorbid.
- Continue to explore broader use, identify newer indications leading to new approvals including the pull-through of late-lifecycle ISR/IST that may have been slow to enroll or complete
- “Pipeline-in-a-product” is oft quoted and rarely achieved yet some products have been highly successful in expanding upon the initial indication, for example Adalimumab (5 indications), Aripiprazole (11 indications) and Pembrolizumab (22 indications and counting), each requiring specific knowledge and insights to be shared with the relevant patient, caregiver and prescriber.
- “Pipeline-in-a-product” is oft quoted and rarely achieved yet some products have been highly successful in expanding upon the initial indication, for example Adalimumab (5 indications), Aripiprazole (11 indications) and Pembrolizumab (22 indications and counting), each requiring specific knowledge and insights to be shared with the relevant patient, caregiver and prescriber.
- Ensure a smooth transition of institutional knowledge to mature business division
- Firms such as Novartis with Sandoz have generic subsidiary businesses, others such as Merck with Organon have divested their post-LoE brands to independent firms. Regardless, there is a core body of scientific and medical information that demands handover and this falls to the MA function.
- Firms such as Novartis with Sandoz have generic subsidiary businesses, others such as Merck with Organon have divested their post-LoE brands to independent firms. Regardless, there is a core body of scientific and medical information that demands handover and this falls to the MA function.
- Inform the value proposition for late-lifecycle drugs that are subject to government price negotiation
- The Biden IRA legislation impacting Medicare-eligible American adults has raised a new, unforeseen demand on biopharma, namely the need to present the value proposition for a product that is potentially in the late-lifecycle phase. The first list of 10 drugs (insert reference) included #X that are within 2 years of LoE and the remaining #Y all fit within our late-lifecycle definition. The MA function is a critical repository of information in such cases.
- The Biden IRA legislation impacting Medicare-eligible American adults has raised a new, unforeseen demand on biopharma, namely the need to present the value proposition for a product that is potentially in the late-lifecycle phase. The first list of 10 drugs (insert reference) included #X that are within 2 years of LoE and the remaining #Y all fit within our late-lifecycle definition. The MA function is a critical repository of information in such cases.
- Inform the value proposition of a drug against generic competition
- Scientific advances can shape our understanding of safe and appropriate use even in the late-lifecycle and post-LoE. Examples include the CYP2C19 biomarker for clopidogrel that emerged about four years prior to LoE and the VKORC1 and CYP2C9 biomarkers for warfarin that emerged more than 40 years after LoE!
Conclusion
The late-lifecycle phase of a branded drug is often viewed as the “less exciting” end of the innovation spectrum, affirmed by dwindling investment, the ultimate transition to generic or biosimilar status, and the departure of many of one’s colleagues to work on the “new, cool, soon-to-launch brand.”
However, ensuring the safe and appropriate use of a drug within the patient and prescriber community in an era of transformative scientific advances requires a depth of knowledge that aligns with MA capabilities. In this article we have outlined six activities specific to the late-lifecycle phase each of which affirm the critical role of MA. By extension, these activities inform the need for adequate resources to support the work, and the recognition that late-lifecycle MA support is as important as the day-of-launch!
Ross Maclean, MD
Ross Maclean, MD is Head of Medical Affairs at Precision AQ. Early in his career he worked in occupational medicine serving as a “flying doc” to the Shell and BP installations in the UK sector of the North Sea as well as roles in hyperbaric, maritime, and mountain medicine, and as a Medical Officer for the British Antarctic Survey.
Uchenna Iloeje, MD
Dr. Uche Iloeje is Senior Vice President, and Head Global Medical Affairs at SpringWorks Therapeutics, a clinical stage biopharmaceutical company based in Stamford Connecticut. He is a Nigerian born and trained physician graduating from The University of Nigeria in 1987. He specialized in Internal Medicine at the University of Connecticut, Critical Care Medicine at the University of Pittsburgh, and Epidemiology and Environmental Health at Yale University. He has been in the pharmaceutical industry for over 2 decades, working in several companies, with experience in health economics and outcomes research, epidemiology, clinical development, medical affairs and payer evidence. Dr. Iloeje has authored or co-authored over 50 peer reviewed articles in high impact journals including, but not limited to JAMA, Hepatology, Gastroenterology, American Journal of Epidemiology, Diabetes Obesity and Metabolism, American Journal of Cardiology, Clinical Infectious Diseases, HIV Medicine, Journal of the National Cancer Institute, Journal of Clinical Oncology, and Pharmacoeconomics.
