- AbbVie Inc. disappointed investors Thursday, revealing it will not seek accelerated approval for its small cell lung cancer (SCLC) drug Rovalpituzumab tesirine, or Rova-T, in the third-line setting due to disappointing topline results from the Phase 2 TRINITY study.
- AbbVie said it will continue the ongoing Phase 3 MERU and TAHOE studies testing Rova-T in first- and second-line SCLC, respectively. Results from those trials are expected in the second half of 2019.
- Shares of the big pharma shed more than 10% in value during morning trading, falling to near $100 per share — well off AbbVie's 52-week high of $125.86.
Rova-T has been one of the more closely watched assets of AbbVie's late-stage pipeline, although some analysts had assigned less value to its prospects. Still, the disappointment casts a shadow over the company's ability to expand its oncology portfolio into solid tumors and creates uncertainty around AbbVie's M&A strategy.
"We continue to believe Rova-T has potential for patients with small cell lung cancer and other DLL3-expressing cancers," said AbbVie's Chief Scientific Officer Mike Severino, in a statement, while acknowledging the results were "not what we hoped for."
AbbVie reported data from 177 patients, representing about 74% of the study's overall population who had high DLL3 expression. Overall response rate reached only 16% despite the narrower cut of the data. Median overall survival, a co-primary endpoint of the study, came in at 5.6 months.
By investigator-assessed best overall response rate, 29% of patients responded to treatment at any time prior to receiving subsequent therapy.
Those numbers are well below investor hopes. In an Oct. 25 note, Leerink analyst Geoffrey Porges noted Rova-T would need to show a median overall response rate greater than 30%, as well as median overall survival beyond five months, to be commercially viable against third-line chemotherapy.
Not only was efficacy lower than expected, but Rova-T also created significant side effects for patients. Results showed 38% of patients experienced fatigue, 32% had a buildup of fluid in the lungs, 31% experienced swelling of the limbs, and 26% reported nausea among other side effects.
"Our analysis causes us to believe that the FDA told the company not to bother filing for accelerated approval given the trial results and the risk/benefit seen in the study," wrote Porges in a March 22 note, who believes the lackluster results will jeopardize about $1.5 billion in future revenue.
AbbVie acquired the compound through its $9.8 billion acquisition of privately held Stemcentrx in April 2016 — one of its largest acquisitions to date. The big pharma paid $5.8 billion upfront, with $4 billion attached in milestones to regulatory and development success.
Rova-T was the most advanced stage compound from the deal, but AbbVie also gained four early stage cancer assets and access to Stemcentrx's antibody drug conjugate (ADC) platform technology.
"In turn these safety liabilities undermine a key component of the Stemcentrx platform, which is their ADC linker chemistry. The adverse events appear to be associated with the toxin included in the ADC, and must be assumed to be a liability for all ADC’s coming from Stemcentrx," added Porges.
AbbVie received pushback from analysts and investors when it acquired Stemcentrx. While the big pharma has built up a stronger presence in hematology, it doesn't have much in the way of solid tumors. The success of Rova-T would be its first step toward a more diversified oncology portfolio.
Rova-T works by targeting the delta-like protein (DLL)-3, which is expressed on small cell and neuroendocrine tumors.