GSK’s two ADCs show encouraging early efficacy, while high-dose safety and competition remain key
Mo-rez achieved a confirmed response rate of 62% in platinum-resistant ovarian cancer, while global data for Ris-rez in small-cell lung cancer were also close to those from a Chinese study. Goldman Sachs sees both assets as competitive, but higher doses were associated with more serious adverse events, and the near-term focus remains oncology drug commercialization.
Original source：Goldman SachsFirst published on Unhidea：Original source date：
Key takeaway
Goldman Sachs is optimistic about the early efficacy and further development potential of GSK’s two ADCs, but intense competition, dose-safety trade-offs and near-term commercialization execution together constrain the realization of their value.
What did longer-term follow-up of Mo-rez show?
In the global phase I BEHOLD-1 study in platinum-resistant ovarian cancer, the confirmed objective response rate in the Mo-rez 5.8 mg/kg every-three-weeks group was 62%; at a median follow-up of 13.4 months, median duration of response was 12.2 months and median progression-free survival was 11.1 months. Goldman Sachs believes these results support advancement to a phase III study.
Efficacy improved with dose: the confirmed response rate in the 4.8 mg/kg group was 57%, and median progression-free survival was 8.3 months; however, median duration of response was 6.9 months, below the 7.8 months in the 2.8 mg/kg group, while it was 12.2 months in the higher-dose group.
Higher doses also came with a safety cost: the incidence of grade 3 or higher treatment-related adverse events was 71% in the 5.8 mg/kg group, versus 49% in the 4.8 mg/kg group; treatment-related serious adverse events were 22% and 13%, respectively.
What does competition mean for Mo-rez?
Goldman Sachs sees platinum-resistant ovarian cancer as an especially competitive area for ADCs. Genmab’s Rina-S phase III trial reported positive primary results, which could raise the competitive bar and change treatment sequencing, potentially affecting opportunities in second-line and subsequent treatment.
GSK management noted that, in cross-trial comparisons, Mo-rez’s phase I confirmed response rate was 62% and median progression-free survival was 11.1 months, higher than the respective 46% and 9.5 months in Rina-S phase I; however, the Rina-S phase III study has so far disclosed only a survival hazard ratio and not median values, limiting direct comparisons.
GSK is also testing Mo-rez combined with a PD-1 drug as maintenance therapy for patients with mismatch repair-proficient endometrial cancer, seeking to expand its use beyond monotherapy.
What are the gains and drawbacks in the global Ris-rez data?
In a global phase I study of second-line treatment for relapsed extensive-stage small-cell lung cancer, the confirmed response rate in the Ris-rez 8 mg/kg every-three-weeks group was 61%, broadly consistent with 58% in an earlier Chinese study; the rate in the global study’s 6 mg/kg group was 32%. The 8 mg/kg group included 18 patients, and the company has selected that dose for phase III development.
The incidence of grade 3 or higher treatment-related adverse events was 42% in the 8 mg/kg group, higher than 15% in the 6 mg/kg group, and 25% of patients required dose reductions. A pooled analysis of two global early-stage studies showed that 4% of 558 patients developed interstitial lung disease, with grade 3 or higher cases below 1%; Goldman Sachs is watching for long-term data from the subsequent global phase III study.
GSK management said whether Chinese data can translate into global results must still be assessed for each drug and indication; differences in lung disease incidence between global and Chinese studies are also affected by patient composition, follow-up duration and how events are identified.
What is the near-term focus for the oncology business?
In the AZUR-1 study of Jemperli in dMMR/MSI-H locally advanced rectal cancer, 68% of patients achieved a clinical complete response at 12 months; at a median follow-up of 26 months, 98% of complete responses remained ongoing. Goldman Sachs noted that near-term attention for the drug remains on litigation developments.
Goldman Sachs believes the two ADCs are beginning to demonstrate competitiveness, but numerous similar and combination therapies are in development, and their potential value will need more data and time to emerge. Meanwhile, oncology drug commercialization remains a priority: investor expectations for Blenrep’s launch performance are low, the bank expects sales of the newly acquired Jidetryo to ramp slowly, and the US regulatory decision date for zidesamtinib is 27 November.
Goldman Sachs maintained its neutral rating on GSK, with a 12-month price target of 1,860 pence per share; the share price cited in the report was 1,923.5 pence, implying approximately 3.3% downside.
