ESMO 2019: surufatinib epNET PFS benefit confirmed
Update | 3 October 2019
The China Phase III SANET-ep surufatinib study in extra-pancreatic neuroendocrine tumours (epNET) was terminated early, in June 2019, having already met its primary endpoint of progression-free survival (PFS) at the planned interim analysis. Detailed data at the 2019 European Society for Medical Oncology (ESMO) meeting disclosed the magnitude of effect: investigator assessed PFS of 9.2 months for surufatinib vs 3.8 months for placebo (hazard ratio = 0.334, p<0.0001), as well as the encouraging broad utility across epNET subtypes. The totality of the SANET-ep data supports a potential Q419 China NDA filing for surufatinib and, subject to regulatory approval, Chi-Med could launch its first wholly owned oncology drug c 12 months later, in late 2020.
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3 October 2019
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Hutchison China MediTech is a Hong Kong headquartered biopharma with an established Commercial Platform in China, and a diverse pipeline of first-in-class/best-in-class selective oral tyrosine kinase inhibitors (Innovation Platform). Its pipeline, discovered in-house, is in development for the China and global oncology markets.
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Mick Cooper PhD
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Table of Contents
Our June 2019 Update note provided an overview of surufatinib, neuroendocrine tumours (NET), the clinical data to date, and Chi-Med’s development plans. Presentation of SANET-ep data at ESMO builds upon this and confirms that surufatinib is on track to become the first of Chi-Med’s unpartnered oncology drugs to reach the market in China.
Positive read out of the pivotal SANET-ep trial in advanced extra-pancreatic NET (epNET) supports a potential China NDA filing in Q419, which, if approval occurs in a similar timeframe to fruquintinib, could lead to surufatinib launch in late-2020 through Chi-Med’s own China Oncology commercial infrastructure.
The potential China opportunity in NET could be significant, as illustrated in Exhibit 1. Important features of this market include the:
NET is the first of many opportunities for surufatinib. The China and Global surufatinib development programme is focused on indications with high unmet need and with potential for a rapid path to market given the relative rarity of the cancer types targeted and limited treatment options.
Newsflow from the current development pipeline includes:
The SANET-ep study (Exhibit 2) was stopped early for efficacy at a planned interim analysis following the IDMC (Independent Data Monitoring Committee) determination that the mPFS (median progression free survival) primary endpoint had been met. The study originally targeted the enrolment of 273 patients but included an interim analysis at 127 PFS events (c 70% of the planned PFS events for the final analysis), with early termination for superiority permitted if p<0.015.
The SANET-ep primary analysis is illustrated in Exhibit 3, where surufatinib showed a statistically significant 5.4 months benefit to mPFS vs placebo. mPFS was 9.2 months on surufatinib vs 3.8 months for placebo (HR 0.334, p<0.0001). Subgroup analyses (Exhibit 4) indicated that all subgroups favoured surufatinib.
As a comparison, the single-arm Phase II China NET trial reported mPFS of 13.4 months for the epNET population (n=40), a result which reflects differences in patient baseline characteristics between the two trials (SANET-ep had a higher proportion of G2 patients with aggressive disease).
PFS sensitivity analysis was carried out retrospectively in parallel by a blinded independent image review committee (BIIRC). There were some discrepancies in tumour image analysis between the investigators and BIIRC assessments (likely to be influenced by prior loco-regional therapies and/or liver lesion CT/MRI characteristics); however, the sensitivity analyses were supportive of the primary PFS analysis (Exhibit 5). Secondary endpoints were also consistent with a treatment benefit with surufatinib.
From a safety perspective, surufatinib was generally well tolerated, with a safety profile consistent with prior data. Proteinuria and hypertension were the most frequent ≥Grade 3 adverse events but were manageable. The drug exposure safety analysis indicated that patients on surufatinib had median exposure of 217 days (c seven months) vs 146 days (c five months) for placebo patients, with a relative dose intensity of 86.42%.
In addition to SANET-ep data, early findings from the US Phase Ib/II solid tumour study of surufatinib (Exhibit 6) were presented at ESMO, providing supportive evidence for the global applicability of the programme. The dose escalation phase of the study confirmed a maximum tolerated dose and recommended Phase II dose of 300mg QD surufatinib, which is consistent with the dosing of the China trials. Dose expansion is ongoing, although preliminary data from the pNET and BTC cohorts were presented. Data from 25 evaluable patients showed two confirmed partial responses (and two unconfirmed partial responses) in pNET patients.
A key takeaway from this study and the surufatinib data generated to date, is that it has shown anti-tumour activity in heavily pre-treated patients and across multiple tumour types. The US Phase Ib/II enrolled patients which had progressed on up to eight lines of prior therapy, and all of whom had progressed on everolimus (Afinitor, Novartis). Exhibit 7 illustrates the duration of treatment in the pNET cohort, highlighting both the number and diversity in the prior lines of therapy experienced.
Everolimus is approved for the treatment of adults with non-functional NETs of gastrointestinal or lung origin, with unresectable, locally advanced, or metastatic disease, and currently has the broadest clinical evidence base across NETs by site of origin (Exhibit 7). Chi-Med, through its SANET-ep and SANET-p pivotal trials – and planned US/European registration trials – is seeking to rival this with surufatinib, to potentially offer a subsequent treatment option for NET patients who progress on everolimus.
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