DUBLIN – Immunomedics Inc. is stopping the phase III Ascent trial of its antibody-drug conjugate, sacituzumab govitecan, in triple-negative breast cancer (TNBC) on the unanimous recommendation of the study’s independent data safety monitoring committee, after a scheduled look at the study data uncovered what the company called “compelling efficacy.” The move triggered an investor frenzy April 6, which propelled the Morris Plains, N.J.-based company’s stock (NASDAQ:IMMU) up by 179% during pre-market trading to a one-year high of $26.25.
Shares ended the day at $18.78, up 99.8%.
“The remarkable results we observed across multiple endpoints in the Ascent study warranted early discontinuation of the trial and are indicative of a potential major advance in the treatment of this devastating disease that affects younger women and African American women at higher rates,” stated committee chairwoman Julie Gralow, of the University of Washington School of Medicine. Immunomedics officials are themselves none the wiser about what precisely prompted the early halt to the study. “The data safety monitoring board saw all of the data for all of the endpoints. We remain blinded to what they actually saw, so we really can’t comment on what their decision was based on,” Immunomedics’ chief medical officer, Loretta Itri, told a conference call audience.
The drug comprises an antibody directed at trophoblast cell-surface antigen 2 (Trop-2), which is expressed on 85% of all cancers, and joined by a cleavable linker to SN-38, an active metabolite of the topoisomerase I inhibitor irinotecan. The cytotoxic drug accumulates both in the tumor microenvironment and within cancer cells. Sacituzumab govitecan is currently under FDA review, on an accelerated approval pathway, and has a PDUFA action date of June 2. That filing is based on an open-label phase I/II study in 110 patients, which delivered an objective response rate (ORR) of 31%, according to independent review, or 34% according to local review. The open-label phase III Ascent trial recruited more than 500 patients with metastatic TNBC who had taken at least two prior therapies. There were randomized, in a 1-to-1 ratio, to receive sacituzumab govitecan or physician’s choice. The primary endpoint of the study is progression-free survival. Overall survival and ORR are two of the key secondary endpoints.
The study was fully recruited last year, and the company had been tracking the number of PFS events as defined by the study protocol. “The PFS events slowed down significantly over the last few months,” Immunomedics’ chief financial officer and chief business officer, Usama Malik, told BioWorld. The company is revising the statistical plan to take account of the lower-than-expected number of events on which the primary analysis will be based. But its reporting timelines are not affected. “We expect top-line data around midyear,” Malik said. The overall survival data are expected to follow later in the year – the company is confident that the drug will be on the market at that point. The pace of interaction between the company and the agency has not slowed, despite the additional pressure on the FDA caused by the COVID-19 pandemic. “Ultimately, it’s the FDA’s decision,” Malik said. “It is possible the FDA could issue an early approval.”
The early trial halt has wiped away investor concerns prompted by a double-downgrade from Goldman Sachs on April 3, which had switched its recommendation from buy to sell and revised its target price from $24 to $5 following the emergence of a nine-page FDA 483 facility inspection report, which listed 33 issues under 10 general observations. A previous inspection report, which uncovered data integrity breaches and substantial quality problems, prompted a complete response letter in January 2019, which led to a management clear-out and a resubmission last December.
The current set of observations is not comparable, however. “We don’t think there are any approvability issues in the 483s,” Malik said. “This time round, the issues are principally around the evolution of the quality system.” The company’s reaction is ongoing. “We have submitted a fulsome response to the FDA and have engaged in a productive dialogue with them. We have already addressed several of the observations and are on track to complete others in the coming weeks and are finishing others as part of our ongoing quality improvement plan,” Executive Chairman Behzad Aghazadeh said on the conference call. “Based on our discussions with the FDA, it is our current understanding that an additional inspection is not warranted.” The company does not expect any further inspections across its supply chain in the present review period, he added.
Immunomedics is commercializing the product in the U.S. itself, and it already has enough product on hand to cater for the first 12 to 18 months of commercialization. “We have a fully built infrastructure for launching in the U.S. in triple-negative breast cancer,” Malik said. Whether its sales force will be knocking on doors or holding teleconferences with oncologists depends on how the COVID-19 pandemic unfolds across the U.S. in the coming months. It may well have to adopt both strategies, depending on location. The company will follow the “heat map” of the outbreak, Malik said, and adjust its plans accordingly.
Cowen & Co. analyst Phil Nadeau offered an upbeat assessment of the drug’s prospects: “There is little question that sacituzumab will soon become standard of care in the treatment of relapsed and refractory mTNBC,” he wrote in a flash note. “The stoppage removes clinical development risk in mTNBC that had concerned some investors.” The outcome of Ascent also “partially derisks” clinical development in relapsed/refractory hormone receptor-positive/HER2-negative metastatic breast cancer. Enrollment onto a phase III trial is ongoing. A phase II trial in urothelial cancer is fully enrolled.
The company has not yet decided whether to go it alone or to pursue a deal in Europe. It has already entered a deal worth up to $835 million with New-York-based Everest Medicines II Ltd., which covers most of Asia, apart from Japan. Its incoming CEO will doubtless have a key role in determining its European strategy, given his experience in that region. Immunomedics named Harout Semerjian as its new president and CEO Monday. He assumes the role on April 16. Semerjian was previously chief commercialization officer at Paris-based Ipsen SA and, before that, he spent 16 years in the oncology business of Basel, Switzerland-based Novartis AG.