AstraZeneca's cancer meds Lynparza, Imfinzi cruise toward blockbuster-land

AstraZeneca’s oncology portfolio put on another good show, with anti-PD-L1 Imfinzi and Merck & Co.-shared PARP inhibitor Lynparza now on track to cross the blockbuster line for the first time in 2019. 

Sales from AZ’s oncology franchise surged 51% in the second quarter to $2.17 billion. That helped push up AZ’s total haul—to $5.72 billion or by 14% to be exact—for the fourth consecutive quarter after years of repeated declines. And it vindicated CEO Pascal Soriot's repeated promise that cancer would help pull the company out of that revenue trough.

EGFR inhibitor Tagrisso, now established as AZ’s top-selling drug in the wake of Crestor's generics fall, delivered $784 million, up nearly 25% quarter over quarter. It's extending its global rollout for first-line non-small cell lung cancer (NSCLC) use—and still expecting a decision for that indication in China, where AZ's already posting strong growth.

Tagrisso’s number beat analysts’ consensus by 12%, and it’s not alone in that sense, either. Lynparza racked up $283 million and Imfinzi registered $338 million, both ahead of the Street’s expectations.

Lynparza's going strong with the help of a U.S. nod for first-line maintenance treatment of BRCA-mutated ovarian cancer in patients who responded to a round of chemotherapy. That same indication has since been approved in the EU and Japan. And it awaits regulatory decisions for BRCA-positive pancreatic cancer after showing it nearly doubled the time patients lived without their disease progressing.

Further, Lynparza’s growth potential probably rests not just in the smaller BRCA-mutated market.

PARP inhibitors historically worked best in women with BRCA mutations, which account for about 15% of ovarian cancer cases. GSK, which snagged rival Zejula in its $5.1 billion Tesaro buy, was testing whether other genetic mutations might respond. And along the way, it found that Zejula could work as a first-line ovarian cancer maintenance therapy for all patients, even those without BRCA mutations.

That positive news for GSK, unveiled earlier this month, could also spell good things for Lynparza. After all, analysts have said the effect in non-BRCA patients is likely shared across the PARP class. And AZ has a huge lead right now. By second-quarter numbers, Zejula sales of £57 million ($71 million) were far behind Lynparza’s. 

AZ is working on its own specific answer to that category, too. A phase 3 trial dubbed Paola is testing Lynparza in tandem with Roche’s Avastin in the exact same setting—first-line ovarian cancer maintenance, regardless of BRCA status—and a readout is expected later this year.

"We’re looking forward to going beyond just single-agent PARP inhibitor, and we do believe that there’s strong evidence that the combination of a VEGF inhibitor—in this case of Avastin—plus Lynparza will further add to the lives of these patients," José Baselga, executive vice president and president of oncology R&D, told reporters during a call Thursday.

GSK has yet to reveal detailed data from the new Zejula study, so it’s still unclear exactly how well the drug worked in nonbiomarker patients. AZ, for its part, believes adding Avastin on top of Lynparza could beat monotherapy in those patients.

"Fifty percent of women across the globe do receive Avastin ... in the front-line setting, and in some countries those women are often going to receive Avastin as maintenance," Dave Fredrickson, the EVP responsible for AZ’s commercial ops in cancer, said during the call.

"We certainly believe that Avastin is an important part of a treatment across the globe in ovarian cancer," he added, "and if there’re compelling results out of Paola, we will certainly see that there’s reason for physicians to consider the combo."

Imfinzi posted its own share of good news after the key Mystic failure in NSCLC last year. In the small-cell form of the disease, combining the PD-L1 with chemo beat chemo alone at extending patients’ lives in a phase 3 trial. If AZ can win FDA approval for that use, it would tee up direct competition with Roche’s Tecentriq.

Now, after first-half 2019 sales of $633 million, the drug is set to cross the blockbuster line this year. There could be more upside as "we are really just getting started in markets outside of the U.S.," Fredrickson said. Later this year, phase 3 trials that evaluate Imfinzi with or without investigational CTLA-4 inhibitor tremelimumab and alongside chemo in first-line NSCLC will also read out.

Elsewhere in AZ’s oncology business, Calquence recently posted late-stage trial wins in both previously treated and treatment-naïve chronic lymphocytic leukemia, and AZ expects to file for approvals later this year. The drug snared $35 million in the second quarter, above expectations.

However, in perhaps a last swing at growth, breast cancer treatment Faslodex grew sales by 8% to $267 million in the quarter. The 21% beat against consensus was also the biggest in the quarter as quoted by Jefferies.  

Novartis’ Sandoz in late May launched its generic version of the AZ drug, so that attack isn't fully reflected in second-quarter numbers. But based on examples of similar cases, Faslodex revenues in the U.S. will decline "quite importantly" over the second half the year, Fredrickson said.

Overall, buoyed by what Wolfe Research analyst Tim Anderson called a "big, high-quality beat" in the second quarter, AZ has raised its full-year sales guidance to low double-digit growth from the previously expected high-single digits.