United Therapeutics' Unituxin Disappoints In SCLC
Impact Likely Minimal On Company's Growth
Executive Summary
Targeting gangliosides expressed on SCLC tumors has been explored by United Therapeutics in the Phase II/III DISTINCT study, but top-line results show no effect on overall survival.
The failure of United Therapeutics Corp.’s Unituxin (dinutuximab) to improve overall survival in small cell lung cancer in the Phase II/III DISTINCT trial has underlined the recalcitrance of the condition.
The study is the second to report disappointing results in SCLC this year, with Merck & Co reporting that Keytruda (pembrolizumab) improved PFS but not overall survival in the KEYNOTE-604 study in patients with extensive-stage SCLC. (Also see "Merck & Co's Keytruda Disappoints In Small-Cell Lung Cancer" - Scrip, 7 Jan, 2020.)
In top-line results from DISTINCT, the addition of the tumor-associated ganglioside GD2-binding monoclonal antibody dinutuximab, to irinotecan therapy did not extend overall survival compared with irinotecan alone, the primary endpoint, in patients with relapsed or refractory SCLC. SCLC tumors express ganglioside 2, the target to which dinutuximab binds.
DISTINCT involved 471 patients evaluated in 198 medical centers in the US, Europe and Asia-Pacific, and the safety profile of dinutuximab in the study was consistent with prior studies and Unituxin’s product label – it is already marketed in the US in combination with GM-CSF, IL-2 and 13-cis-retinoic acid for pediatric patients with high-risk neuroblastoma who have achieved at least a partial response to first-line therapy.
Full Data Awaited
Subgroup analyses and updates are awaited, although analysts at Informa Pharma’s Biomedtracker believe the continued development of dinutuximab in SCLC appeared unlikely.
Recent trial data in previously treated SCLC with other medicines have not shown improvement over topoisomerase inhibitors (irinotecan, topotecan, amrubicin) which are often used in this patient subset, the analysts note.
For example, though Bristol-Myers Squibb Co.’s Opdivo (nivolumab)’s accelerated approval for previously treated SCLC was supported by the single-arm Phase I/II CheckMate-032 trial, the drug failed to improve response rates or survival endpoints compared with topotecan or amrubicin in the confirmatory Phase III CheckMate-331 trial, the analysts point out. (Also see "Bristol’s Checkmate-331 Failure Not Likely To Endanger SCLC Labeling For Opdivo" - Scrip, 12 Oct, 2018.)
And Merck & Co. Inc.’s Keytruda (pembrolizumab) received accelerated approval in previously treated SCLC based on two open-label trials, KEYNOTE-158 (Cohort G) and KEYNOTE-028 (Cohort C1), but neither had a chemotherapy comparator.
Analysts at Credit Suisse said they believed the DISTINCT results would only have a minimal impact on its constructive outlook for United Therapeutics, which is centered on a slower than expected uptake of generic competitors to its treprostinil products.
Other Indications
Unituxin garnered sales of $30.1m in the third quarter of 2019, up by 31% on the 2018 third quarter, and an SCLC indication would have extended the use of Unituxin outside of the niche neuroblastoma area.
Nonetheless, the company is also pursuing a label expansion for Unituxin for use with irinotecan and temozolomide for the treatment of pediatric patients with relapsed or refractory neuroblastoma, based on the results of the ANBL1221 study. A meeting with the US FDA in the first half of 2020 could be followed by the filing of a supplemental biologics license applications (sBLA).
Silver Spring, MD and Research Triangle Park, NC-based United will also now turn to the results of another late-stage study, INCREASE, for good news, with results expected by the end of the first quarter or shortly thereafter. INCREASE is a Phase II/III study of the marketed product, Tyvaso (inhaled treprostinil), in patients with pulmonary hypertension due to interstitial lung disease.
United Therapeutics reported another late-stage clinical trial setback in April 2019, when esuberaprost tablets missed the primary endpoint of delayed time to first clinical worsening event in patients with pulmonary arterial hypertension in the BEAT study. (Also see "Missed BEAT Removes Tough Sell For United Therapeutics" - Scrip, 9 Apr, 2019.)