AZ Pushes Further Ahead In PARP Race With Lynparza/Avastin Combo
Executive Summary
The PAOLA-1 study has shown the benefit of Lynparza for ovarian cancer patients regardless of tumor mutation status which should firm up the drug's dominance in the PARP inhibitor space.
AstraZeneca PLC's efforts to consolidate Lynparza as the market-leading PARP inhibitor have received a further boost from a closely watched study, the results of which could widen the drug’s use among patients with advanced ovarian cancer regardless of their genetic mutation.
The company and partner Merck & Co. Inc. have announced positive top-line results from the Phase III PAOLA-1 trial in the first-line maintenance setting which compared Lynparza (olaparib) added to Roche's standard-of-care Avastin (bevacizumab) versus Avastin alone in women with or without BRCA gene mutations. The study met its primary endpoint of demonstrating a statistically significant and clinically meaningful improvement in progression-free survival.
The safety and tolerability profiles observed in PAOLA-1 were generally consistent with those known for each medicine, AstraZeneca said. The results, including biomarker sub-group analyses, will be presented at a forthcoming medical meeting, which could be as soon as European Society for Medical Oncology (ESMO) congress being held in Barcelona at the end of September.
Lynparza became the first PARP inhibitor to be approved by the US Food and Drug Administration as first-line monotherapy maintenance treatment in December 2018 based on stellar PFS data from the pivotal SOLO-1 study, presented at ESMO last year. However, that approval covers only BRCA-positive patients and that mutation is only found in around 20% of ovarian cancer patients, so the success of PAOLA-1 in a broader patient population augurs well for expanded use. (Also see "First-Line Ovarian Cancer Approval Solidifies Lead For AstraZeneca's Lynparza " - Scrip, 19 Dec, 2018.)
In an interview with Scrip following AstraZeneca's second quarter financials, the group's oncology head Dave Fredrickson said that Avastin, a VEGF inhibitor, was the best comparator because 50% of women across the globe receive it as a therapy in the frontline setting and in Europe, almost all of those getting it as induction are on Avastin as maintenance. Now that PAOLA-1 has shown that there is a benefit to adding Lynparza on top of an Avastin backbone, Fredrickson believes that given physicians' familiarity with the Roche drug, there could be wide uptake of the combo. Oncology R&D chief José Baselga said, "We look forward to discussing the results with global health authorities as soon as possible.” (Also see "AZ On The Rise In All Regions And Therapy Areas " - Scrip, 25 Jul, 2019.)
Merck R&D chief Roy Baynes pointed out that the trial was a co-operative group study sponsored by Arcagy-Gineco, a non-profit independent research group and Lynparza was evaluated "in an environment representative of real clinical practice." Arcagy medical director Eric Pujade-Lauraine added that PAOLA-1 was “a positive example of the strength and promise of academia-industry collaboration in advancing science and new treatment options."
The results from PAOLA-1 will be keenly followed by GlaxoSmithKline PLC. The company is hoping that its PARP inhibitor Zejula (niraparib), acquired through the $5.1bn buy of Tesaro Inc., could have an edge as a first-line maintenance therapy in ovarian cancer based on results from the recent positive Phase III PRIMA trial in the broad population.
The double-blind, placebo-controlled study met its primary endpoint of a statistically significant improvement in progression free survival for women regardless of their biomarker status, GSK reported on 15 July. The UK drugs major did not provide detailed results from the trial and said it would present the data at an upcoming medical meeting, so there is a distinct possibility that PAOLA-1 and PRIMA will face off at ESMO next month.
Zejula, however, has an awful lot of ground to make up on Lynparza, which saw second quarter sales double to $283m. The GSK drug, which is currently approved as a maintenance therapy for second-line but not first-line ovarian cancer, brought in £57m in Q2.
The PAOLA-1 data is the latest in a long line of successes for Lynparza in the clinic. Just last week, AstraZeneca and Merck presented topline data from the PROfound study which showed a statistically significant and clinically meaningful improvement in the primary endpoint of radiographic PFS with Lynparza, compared with Pfizer Inc.'s Xtandi (enzalutamide) or Johnson & Johnson's androgen receptor inhibitor Zytiga (abiraterone) in men with metastatic castration-resistant prostate cancer selected for BRCA 1/2 or ATM gene mutations. (Also see "PROfound Puts Lynparza On Track For Prostate Cancer Indication " - Scrip, 7 Aug, 2019.)
Lynparza, which is also approved for metastatic breast cancer, is also expected to get the green light in pancreatic cancer following the POLO study, which was reported in June at the American Society of Clinical Oncology meeting. (Also see "AZ/Merck & Co’s Lynparza POLO Study ‘Practice Changing’ For Pancreatic Cancer Subgroup " - Scrip, 3 Jun, 2019.)
Breakthrough Status For Calquence in CLL
Rounding off a good day for the company, AstraZeneca also announced that the FDA has granted breakthrough therapy designation (BTD) for Calquence (acalabrutinib) as a monotherapy for adults with chronic lymphocytic leukemia (CLL).
The Bruton tyrosine kinase (BTK) inhibitor was granted accelerated approval for relapsed and refractory mantle cell lymphoma in 2017. CLL represents a much larger opportunity and this summer, AstraZeneca has posted positive results from two trials for that indication. (Also see "AZ’s Calquence Hits Endpoint In Second CLL Phase III Study" - Scrip, 6 Jun, 2019.) (Also see "Positive CLL Data For AstraZeneca's BTK Inhibitor Prompts Early ASCEND Trial End " - Scrip, 7 May, 2019.)
Calquence is also being developed by AstraZeneca and partner Acerta Pharma BV for the treatment of multiple B-cell blood cancers, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, multiple myeloma and other hematologic malignancies.
Baselga noted that getting BTD for CLL "acknowledges the growing body of evidence that supports Calquence as a highly-selective BTK inhibitor with the potential to offer patients a new, differentiated, chemotherapy-free treatment option with a favourable safety profile.”