Bayer Quietly Claims Its Liver Cancer Prize

| About: Bayer A.G. (BAYRY)
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Bayer (OTCPK:BAYRY) will this week claim an important prize for its multi-kinase inhibitor Stivarga as the new standard of care for second-line treatment of unresectable hepatocellular carcinoma.

The positive outcome of its Resorce trial will have important commercial implications for the group, especially given the approaching patent expiry on Nexavar. It might be savvy to conduct studies to move Stivarga up to the first-line setting, but here Bayer would face competition from Eisai’s Lenvima and Bristol-Myers Squibb’s (NYSE:BMY) Opdivo, which are both already in such trials (see tables below).

The German group yesterday disclosed the data it will present at the World Congress on Gastrointestinal Cancer on Thursday from Resorce, its pivotal study of Stivarga. These show that its drug conferred a statistically significant 2.8-month survival advantage in second-line HCC, with a 38% reduction in the risk of death.

Resorce study results

Stivarga

Placebo

Stats

Median OS*

10.6 months

7.8 months

HR=0.62 (p<0.001)

Median PFS

3.1 months

1.5 months

HR=0.44 (p<0.001)

Median TTP

3.2 months

1.5 months

HR=0.46 (p<0.001)

Disease control rate

65.2%

36.1%

p<0.001

Overall response rate

10.6%

4.1%

p=0.005

*primary endpoint.

This level of benefit should be sufficient to ensure that Stivarga becomes the new standard for patients failing on or intolerant to first-line HCC treatment, which is Bayer’s own Nexavar.

Bayer disclosed that the 573-patient Resorce study had rendered a positive outcome some two months ago, but it held the full data back for presenting fresh to oncologists this week. However, it managed to do so with such a lack of ballyhoo that few noticed, which was all the more remarkable given that the study had broken a decade-long run of negative results in HCC.

Of course Stivarga has already been launched for other indications – colorectal cancer and gastrointestinal stromal tumors – though sales are modest, reaching $347m last year. Given its commercial availability patients might get the drug ahead of a formal HCC approval, which will probably come in 2017.

Competition looms

If the Stivarga data do prompt a move into first-line use Bayer must keep an eye on two ongoing HCC studies in this setting: Eisai’s Reflect trial of Lenvima is to render results in December, while Bristol’s CheckMate-459 study of Opdivo is projected to report in May 2017.

Lenvima has shown very strong early results, with a median time to progression of 7.4 months and a median OS of 18.7 months in a single-arm phase I/II trial. At the recent Asco meeting Bristol presented updated findings from its phase II Checkmate-040 study, which showed a 15% overall response rate.

It also reported preliminary data from a dose expansion in 206 HCC patients, which showed an ORR of 9%, with 14% in non-HCV/HBV infected Nexavar-naive/intolerant patients, and 7% in uninfected Nexavar progressors.

Phase III trials in advanced hepatocellular carcinoma

Project

Company

Trial name

Design

Trial ID

Data due

Localised first line

Therasphere

BTG

Yes-P

vs Nexavar

NCT01887717

Jun 2019

Therasphere

BTG

Stop-HCC

Nexavar +/-

NCT01556490

Jul 2019

First line

Cometriq

Exelixis

Celestial

vs placebo

NCT01908426

Oct 2016

Lenvima

Eisai

Reflect

vs Nexavar

NCT01761266

Dec 2016

Opdivo

BMS

CheckMate 459

vs Nexavar

NCT02576509

May 2017

Pexastimogene devacirepvec

Sillagen/Transgene

Phocus

Nexavar +/-

NCT02562755

Oct 2017

Donafenib

Suzhou Zelgen

-

vs Nexavar

NCT02645981

Dec 2018

Second line

Tivantinib

Daiichi Sankyo/Arqule

Metiv-HCC

vs placebo

NCT01755767

Dec 2016

Tivantinib

Kyowa Hakko Kirin

Jet-HCC

vs placebo

NCT02029157

Dec 2016

Apatinib

Jiangsu HengRui

-

vs placebo

NCT02329860

Jan 2017

Livatag

Onxeo

Relive

vs BSC

NCT01655693

Jul 2017

Cyramza

Lilly

Reach-2

vs placebo

NCT02435433

Oct 2017

As such a possible move of Stivarga to the first-line setting has benefits and risks for Bayer, but there are also perils from not doing anything. There are two agents in pivotal studies for second-line HCC that are due to read out this year: Exelixis’ (NASDAQ:EXEL) Cometriq and Arqule’s tivantinib.

Exelixis will be looking to gain an additional indication for Cometriq after its recent success in renal cell carcinoma, while Arqule and its partners Kyowa Hakko Kirin and Daiichi Sankyo are targeting patients with high c-met.

EP Vantage had forecast that progress would come in the HCC field just a few months ago (Hopes rise for a liver cancer breakthrough in 2016, February 19, 2016). Perhaps more will follow.

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