Disease Analysis: Ovarian Cancer
|出版日||ページ情報||英文 109 Pages
|疾患分析：卵巣癌 Disease Analysis: Ovarian Cancer|
|出版日: 2020年04月01日||ページ情報: 英文 109 Pages||
Datamonitor Healthcare estimates that in 2018, there were 293,300 incident cases of ovarian cancer worldwide in females aged 15 years and older, and forecasts that number to increase to 319,500 cases by 2027. Highly genericized platinum-containing chemotherapies are still the standard of care for both newly diagnosed and recurrent platinum-sensitive ovarian cancer patients.
The overall likelihood of approval of a Phase I ovarian cancer asset is 4.4%, and the average probability a drug advances from Phase III is 27.3%. Ovarian cancer drugs, on average, take 10.5 years from Phase I to approval, compared to 9.3 years in the overall oncology space.
Avastin has become the drug of choice for the maintenance treatment of ovarian cancer patients who do not have a BRCA mutation. However, upcoming patent expiries and expected competition from label expansions for the poly (ADP-ribose) polymerase (PARP) inhibitors and late-phase pipeline drugs will challenge Avastin's position in the ovarian cancer market.
The PARP inhibitor Lynparza has quickly become the standard of care first-line maintenance therapy for patients with BRCA mutated ovarian cancer in the US and EU. However, the PARP inhibitors Zejula and veliparib will soon compete with Lynparza in this treatment setting. Although all three PARP inhibitors have also demonstrated an advantage over chemotherapy in patients without a BRCA mutation or a homologous recombination deficiency (HRD), the primary benefit was derived in patients with BRCA or other HRD mutations, which may limit uptake in the broader patient population.
Rubraca, another PARP inhibitor, has experienced only moderate uptake in the US and the EU as a maintenance treatment for recurrent platinum-sensitive ovarian cancer, and in the US as a third-line or later treatment for BRCA mutation-positive (BRCAm+) patients. However, a potential combination with Opdivo in the first-line maintenance setting may expand Rubraca's commercial potential.
New product launches will play a pivotal part in future market dynamics over the next decade. Key new product launches will include checkpoint inhibitors, folate receptor alpha (FRα)-directed antibody-drug conjugate mirvetuximab soravtansine, the targeted anti-cancer viral-based gene therapy agent ofranergene obadenovec, and the VEGF inhibitor Recentin.
The inclusion of PARP inhibitors in the treatment paradigm has led to a subsequent increase in testing for germline and somatic BRCA1/2 mutations as well as genomic instability score (GIS). This trend of using biomarkers to inform treatment decisions will continue with the introduction of checkpoint inhibitors and mirvetuximab soravtansine, which will likely require PD-L1 and FRα testing, respectively.
Several PD-1/PD-L1 inhibitors - dostarlimab, Opdivo, Keytruda, Tecentriq, and Imfinzi - are in late-phase development in combination with carboplatin and paclitaxel with or without concurrent bevacizumab in the front-line and first-line maintenance setting. Because of the likely clinical similarities between drugs within this class, companies developing checkpoint inhibitors will seek to use label expansions into other treatment settings, such as the recurrent setting, to differentiate their products and increase the size of the potential patient population.
As platinum resistance continues to be the primary contributor to mortality in ovarian cancer patients, effective treatments for platinum-resistant or platinum-refractory ovarian cancer remain the largest unmet need within the indication. Treatment for platinum-resistant/refractory ovarian cancer is largely palliative and patients currently have very limited treatment options.
There are no routine screening methods recommended by medical or professional organizations because screening techniques using single tests or combined algorithms have not been shown to reduce all-cause or disease-specific morbidity or mortality. Research to address this unmet need through the development of reliable screening and diagnostic tools that detect early-stage ovarian cancer is ongoing.
Key recent events include Opdivo's Phase III failure as a monotherapy treatment for platinum-refractory recurrent ovarian cancer in ONO-4538-23, and a positive subgroup analysis for mirvetuximab soravtansine in the Phase III FORWARD I study.
Key upcoming catalysts for 2020 include topline results for the Phase III IMagyn050 study of Tecentriq and Avastin, the Phase III OVAL study of ofranergene obadenovec and paclitaxel, and the pivotal Phase II CONCERTO study of Recentin and Lynparza.