Olapali Combination Therapy Approved By FDA

- May 21, 2020-

FDA approves AstraZeneca and Merck ’s PARP inhibitors olaparib (olaparib, English trade name Lynparza) in combination with Roche ’s Avastin as first-line maintenance therapy for ovarian cancer, including initial treatment of platinum-based chemotherapy plus Avastin Responding patients and female patients with BRCA mutations.


Just about a week ago, FDA approved GlaxoSmithKline ’s Zejula (Chinese trade name: Zele, generic name: niraparib, niraparib) for use in first-line platinum-based chemotherapy regardless of biomarker status. Or single-response maintenance treatment for female patients with advanced epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer with partial response.


In contrast, Lynparza's approval is not as broad as Zejula. Although Lynparza combined with the Avastin combination can reduce the risk of disease or death in patients without homologous recombination defects (HRD) by 8%, the FDA has not explicitly approved its use in the treatment of such patients.


AstraZeneca Executive Vice President and Head of Oncology Immunization Dave Frederickson said: "This approval represents another milestone for Lynparza in patients with ovarian cancer. Extending the median progression-free survival period and delaying this difficulty for women with disease The recurrence of curative diseases provides new hope. These results further prove that HRD positive is a unique subset of ovarian cancer, and HRD testing has now become a key component in the diagnosis and adjustment of treatment for women with advanced ovarian cancer. "About half of the patients have Women with advanced ovarian cancer have a positive HRD. For patients with advanced ovarian cancer, the main purpose of first-line maintenance therapy is to delay disease progression as long as possible.


Dr. Roy Baynes, senior vice president of Merck Research Laboratory and head of global clinical development, said, "Understanding the progress of biomarker and PARP inhibition has fundamentally changed the way doctors treat this highly aggressive tumor. Today is based on The approval of the PAOLA-1 trial highlights the importance of HRD testing in diagnosis to identify those who may benefit from Lynparza in combination with Avastin as first-line maintenance therapy. "


The U.S. regulatory agency ’s decision to approve was mainly based on Lynparza ’s phase 3 trial data. The data showed that the patients taking the combination drug reached a median time of 22.1 months without worsening, compared with 16.6 women receiving Avastin plus placebo month. Last year, AstraZeneca and Merck announced these results at the European Society of Medical Oncology Annual Meeting (ESMO) held in the fall, and GlaxoSmithKline, a competitor, also vigorously promoted positive trial data in support of Zejula.


Now, due to the overlap of indications, these two schemes will go hand in hand in the market to compete fiercely. In addition, Zejula will directly fight Avastin in the HRD patient population alone. Leerink Partners analyst Andrew Berens wrote in a report to clients last Friday: "We think Zejula has excellent business prospects among the HRD population. In this market, the drug will need to compete with Avastin to gain market share. In addition to a wider range of indications, Glaxo Zejula may also have an advantage in the convenience of taking medication. Zejula is in the form of pills, which patients can take on their own without the troubles caused by infusion of Avastin, especially during the new coronary pneumonia pandemic, when patients try to stay at home as much as possible.


It is worth noting that Axel Hoos, senior vice president and head of oncology at Glaxo, said in a recent interview that adding a second drug to the mixture can also cause additional toxicity. However, at ESMO, Dave Fredrickson, executive vice president and global head of AstraZeneca ’s oncology business, emphasized that “it is not a combination of the two drugs, and the toxicity will be superimposed, although the side effects are different from Lynparza alone. But we think the benefits of this combination therapy are more obvious. " In addition, Berens also believes that Lynparza is expected to maintain its current leading position among BRCA-positive patients.


Although only time will tell which solution will lead the market, for now, Lynparza has maintained its leading position in PARP therapy.


So far, it is the first therapy in the field to successfully enter the field of ovarian, breast and pancreatic cancer, and it is competing with Clovis Oncology's Rubraca and also entering the field of prostate cancer.


In addition, the European Union, Japan and other countries or regions are currently conducting regulatory reviews of Lynparza and Avastin as first-line maintenance treatment for patients with advanced ovarian cancer.