Ipsen’s Onivyde Hits Bullseye In Pivotal First-Line Pancreatic Cancer Trial
But Observers Waiting To Raise Sales Projections
Executive Summary
The French firm’s Onivyde has succeeded as part of a combination regimen in chemotherapy-naïve pancreatic cancer patients, setting it up for a label expansion, but some experts are keen to see survival data in full before raising guidance.
Ipsen SA’s Onivyde (irinotecan liposome injection) has met the primary endpoint of overall survival (OS) in a Phase III trial in untreated pancreatic cancer patients, sparking filing plans, but potential sales depend on data yet to be released, some observers say.
The Phase III NAPOLI 3 trial set Onivyde plus oxaliplatin (Sanofi’s Eloxatin) and 5 FU/LV against gemcitabine (Eli Lilly and Company’s Gemzar) plus nab-paclitaxel (Bristol Myers Squibb Company’s Abraxane) in more than 7,000 chemotherapy-naïve metastatic pancreatic ductal adenocarcinoma (mPDAC) patients.
Ipsen’s treatment regimen, named NALIRIFOX, met the primary endpoint of OS as well as the key secondary endpoint of improvement in progression-free survival (PFS), with a safety profile similar to previous studies. The firm said full data would be presented at an upcoming medical conference, adding it plans to file a supplemental new drug application with the US Food and Drug Administration in mPDAC, although it did not provide details on timing. NALIRIFOX has a fast-track designation from the US regulator.
Pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer with around 60,000 people diagnosed in the US each year. The cancer is difficult to detect and often diagnosed once the disease has become metastatic. Less than 20% of people with the condition survive past one year and current standard-of-care is limited to chemotherapy regimens such as modified FOLFIRINOX or nab-paclitaxel and gemcitabine.
Onivyde first won FDA approval back in 2015 in combination with fluorouracil and leucovorin for the treatment of metastatic pancreatic cancer that had progressed after gemcitabine-based chemotherapy. The product is a long-circulating, liposomal topoisomerase inhibitor designed to interrupt DNA replication in cancer cells.
Ipsen’s head of R&D Howard Mayer claimed, “The positive results from the NAPOLI 3 trial demonstrate that compared with the standard-of-care, the investigational Onivyde treatment regimen extended the lives of people living with mPDAC who were previously untreated.”
However, observers are waiting on full data to judge whether NALIRIFOX has truly surpassed standard-of-care. FOLFIRINOX attained a median OS of 11.1 months in the mPDAC population in the Phase III ACCORD 11 trial, which is higher than the 8.5 month median OS achieved by gemcitabine plus nab-paclitaxel in its pivotal trial, J.P. Morgan analyst Richard Vosser highlighted in a 9 November note.
Vosser explained that the current €150m sales projection for the Onivyde regimen in first-line mPDAC in 2026 could be raised to more than €500m if the pivotal data show OS superiority over FOLFIRINOX. Meanwhile, the median PFS bars to beat are 5.5 months for gemcitabine plus nab-paclitaxel and 6.4 months for FOLFIRINOX.
Regardless, the NAPOLI 3 success represents a positive twist in Onivyde’s fate after label expansion efforts in small cell lung cancer fell flat earlier this year due to a Phase III miss. The news also represents another milestone in Ipsen’s broader efforts to ramp up its oncology offering. (Also see "Ipsen’s Onivyde SCLC Dreams Die With Phase III Failure, Focus Shifts To Pancreatic" - Scrip, 3 Aug, 2022.)
The firm nabbed the rights to Onivyde under a $575m acquisition of Merrimack Pharmaceuticals, Inc. back in 2017, a move that has paid off so far with the drug raking in €38.8m in sales in the third quarter. Overall, the French firm’s oncology franchise made €603.1m in the same period.
Investments Focus On New Cancer Science
Ipsen has made several other strategic moves within the anticancer space of late, including the acquisition of Epizyme, Inc. earlier this year which brought the first-in-class, chemotherapy-free EZH2a inhibitor Tazverik (tazemetostat) into its fold. (Also see "Ipsen Hungry For More Deals After Swallowing Epizyme" - Scrip, 27 Jun, 2022.)
More recently, the French firm inked a deal with Marengo Therapeutics, Inc. potentially worth $1.59bn to get access to two preclinical assets based on the latter’s proprietary STAR platform, which is designed to boost cancer patients’ T-cells while improving selectivity and flexibility to generate a more robust immune response. (Also see "Ipsen Expands In Oncology With New Pacts" - Scrip, 1 Aug, 2022.)