Although development of interventions for emerging infectious diseases (EIDs) has traditionally been limited by a lack of market incentives, novel funding mechanisms and global partnerships for outbreak preparedness are expanding the commercial prospects for vaccine developers, according to GlobalData, a leading data and analytics company.
The company’s latest report: Vaccines for Emerging Infectious Diseases: Funding, R&D, and Global Partnership Strategies, finds that philanthropic organizations and public-private partnerships like the Coalition for Epidemic Preparedness Innovations (CEPI) are filling a niche for funding translational and clinical vaccine research, allowing development of vaccines for diseases such as Lassa fever to occur even in the absence of an ongoing epidemic. As of November 2018, there were 235 vaccines in preclinical investigation, clinical development, or marketed for twelve major EIDs.
“EIDs are uniquely challenging for vaccine development due to unpredictable clinical incidence or geographical patterns. In response to recent global outbreaks, such as the 2013-2016 West African Ebola epidemic, global partnerships have been formed to stimulate vaccine development with a blend of push and pull market incentives. Chief among these are advanced market commitments (AMCs) from health organizations to subsidize vaccine development by purchasing a vaccine before licensure.”
Paul Jeng, PhD, Infectious Diseases Analyst at GlobalData
GlobalData’s report also finds that 90.2% of marketed or experimental vaccines for major EIDs are still in preclinical or clinical development, leaving significant opportunity for drug developers to enter relatively open disease landscapes for numerous indications.
Jeng continues, “There is a wide gap in the stage of vaccine development for different EIDs. For instance, there have been 57 planned, ongoing, or completed clinical trials for vaccines to prevent Ebola virus disease, and Merck’s Phase III product, V920, is expected to receive FDA approval in 2019. However, the majority of EIDs do not have any licensed vaccine products. Some EIDs including Middle East Respiratory Syndrome (MERS) and Crimean-Congo Hemorrhagic Fever (CCHF) have had experimental vaccines tested in fewer than six clinical trials.”
“KOLs interviewed by GlobalData believed that regulators and vaccine developers are moving towards adaptive clinical trials that factor in rapid surges and declines in disease incidence. Instead of requiring a single large, randomized Phase III trial for vaccine approval, new strategies include collecting and combining data across multiple outbreaks, and expanding avenues for post-marketing studies to evaluate safety and clinical benefit,” concludes Jeng.
Merck and AstraZeneca’s Lynparza well positioned
Sustain dominance of PARP inhibitor market
Merck and AstraZeneca’s Lynparza has been approved by the FDA for first-line maintenance therapy of BRCA-mutated ovarian cancer.
“Lynparza is now the first PARP inhibitor to be approved as maintenance therapy for ovarian cancer in the first-line setting and will most likely continue to dominate the PARP inhibitor landscape. Results from the Phase III SOLO-1 trial published in October 2018 showed that 60% of patients who received Lynparza following platinum-based chemotherapy remained progression-free at three years. Considering that nearly 70% of women with advanced ovarian cancer relapse within three years of their initial treatment, Lynparza is positioned to fill a major unmet need for newly-diagnosed patients.
According to GlobalData’s report: ‘PARP Inhibitors in Oncology’ the total diagnosed incident cases of ovarian cancer with associated germline BRCA1/2 mutations are expected to increase over the next 10 years in the eight major markets (8MM), reaching 11,267 by 2027.
GlobalData’s primary and secondary research indicates that most clinicians view the clinical efficacy profiles of currently marketed PARP inhibitors as roughly equivalent. Merck and AstraZeneca have successfully capitalized on Lynparza’s first-to-market status to build its class leading position through label and geographic expansion, winning the first approvals for a PARP inhibitor in China and Japan for treatment of platinum-sensitive recurrent ovarian cancer.
On 20 December Merck and AstraZeneca also announced positive results from the Phase III SOLO-3 trial of Lynparza in patients with BRCA-mutated, relapsed ovarian cancer after two or more lines of chemotherapy. There remains opportunity for the partners to continue label expansions for Lynparza in ovarian cancer, both as maintenance and treatment monotherapy as well as combination therapy.
Although Tesaro’s Zejula and Clovis Oncology’s Rubraca also have approvals in ovarian cancer, it is unlikely that either drug will challenge Lynparza’s position in this indication. Zejula is currently under investigation in the Phase III PRIMA trial for first-line monotherapy treatment of ovarian cancer regardless of BRCA-mutation status, with results expected in late 2019.”
Paul Jeng, Pharma Analyst at GlobalData
Reshape the pharmaceutical industry
Immuno-oncology drug development and personalized medicine
Immuno-oncology (I-O) drug development will remain at the forefront of the pharmaceutical industry in 2019, says GlobalData, a data and analytics company.
The company’s latest annual outlook report, ‘The State of the Biopharmaceutical Industry – 2019’, reveals that 31% of global industry respondents believe that immuno-oncology will have the greatest impact on the pharmaceutical sector in 2019 among a range of industry trends.
“Immuno-oncology therapeutics have already been proven effective in the treatment of a range of cancers, including melanoma, kidney cancer, lymphoma, and other malignancies. The pace of immuno-oncology R&D remains rapid and its scope has expanded to include combination treatment. More and more, this therapeutic approach is regarded as a potential game-changer. Despite some trial disappointments in 2018, in 2019 we will see more development, more approvals, and more uptake for I-O drugs.”
Claire Herman, Global Director of Therapy Analysis and Epidemiology at GlobalData
The related field of personalized medicine is likewise expected to play a pivotal role in the industry during the coming year, with 19% of survey respondents identifying it as the most impactful anticipated trend. Personalized medicine spans disease areas and stands to transform not just cancer therapy, but the treatment paradigm across multiple diseases.
Herman continues, “Personalized medicine is revolutionizing disease treatment and patient outcomes. In recent years, as the direction of drug development has shifted from a one-size-fits-all blockbuster model to a more finely targeted approach that aims to develop drugs with higher efficacy in specific patient subpopulations, new targeted drugs have begun reaching the market across multiple indications. These new drugs are overhauling the treatment paradigm.”
“While successful implementation of a personalized medicine-driven strategy requires a fundamental shift in the commercial model for most Pharma companies, the investment is worthwhile. In fact, over time, it is likely that targeted therapies will be the standard of care in a wide range of diseases.”
The fact that, taken together, more than half of survey respondents identified I-O or personalized medicine as the trend expected to have the greatest impact on the industry in 2019 is an indicator of the optimism surrounding these new directions. Other trends, including real-world evidence, remote patient monitoring, and biosimilar uptake, were also highly rated. But ultimately, industry stakeholders believe that trends closer to the clinic will have the most transformative short-term effect.
Merck and Pfizer
Update on Javelin Ovarian 100 Trial
Merck and Pfizer Inc. announced that data from a planned interim analysis of the Phase III Javelin Ovarian 100 study of avelumab did not support the study’s initial hypothesis, and therefore the alliance made the decision to terminate the trial in alignment with the independent Data Monitoring Committee.
The Merck-Pfizer alliance was the first to test an immunotherapy in this indication, given the significant unmet need in the treatment of ovarian cancer. Four out of five women with ovarian cancer are diagnosed at advanced stages.1 Most women with advanced ovarian cancer ultimately die within five years due to refractory, resistant or recurrent disease.
Topline results showed that the study, which is evaluating avelumab in combination with and/or following platinum-based chemotherapy in previously untreated patients with ovarian cancer, would not achieve superiority in the pre-specified primary endpoint of progression-free survival. While detailed analyses of the data are ongoing, no new safety signals were observed, and the safety profile for avelumab in this trial appears consistent with that observed in the overall Javelin clinical development program. The alliance has notified health authorities and trial investigators of the interim findings and the decision to discontinue the trial. Detailed results will be shared with the scientific community. The Javelin Ovarian Parp 100 study and earlier phase studies investigating avelumab in various combinations are ongoing.