NewLink’s pancreatic cancer candidate fails to Impress

The phase III failure of NewLink Genetics’ algenpantucel-L is not only a blow to the company, it also dashes hopes of getting a new pancreatic cancer therapy approved any time soon. Of the four pivotal trials in the disease that were due to read out this year, three have already fizzled out (see tables below).

The final study set for results in 2016 also involves algenpantucel-L, so is not looking too hopeful either. While other companies continue to try their luck in pancreatic cancer, NewLink’s focus will shift to its IDO inhibitors indoximod and GDC-0919 – members of a new immuno-oncology class that is seeing increasing interest.

However, on a call to discuss the latest results, the company did not commit to dropping the HyperAcute cellular immunotherapy platform on which algenpantucel-L is based, instead saying it was evaluating its future. An announcement is expected in “weeks rather than months”, according to its chief financial officer, Jack Henneman.

It seems likely that the platform will be wound down after algenpantucel-L’s disastrous performance in Impress, which would also mean the end of NewLink’s other HyperAcute programmes including its phase III non-small cell lung cancer vaccine tergenpumatucel-L and phase II melanoma therapy dorgenmeltucel-L.

Shifting landscape

Earlier this year there was optimism in the pancreatic cancer space, with 10 phase III studies under way involving eight agents (Pancreatic cancer 2016: this time it’s (getting) personal, February 5, 2016). 

But since then, two of these assets – Incyte’s Jakafi and Immunomedics’ Y-90 clivatuzumab – are no longer in development for pancreatic cancer after failing interim analyses. Algenpantucel-L now looks set to join them, unless it can pull off a positive result in the ongoing Pillar study, which has a primary completion date of December 2016.

Recent pancreatic cancer phase III setbacks
Project Company Study Status Trial ID
Jakafi Incyte Janus-1 Discontinued Feb 2016 NCT02119663
Jakafi Incyte Janus-2 Discontinued Feb 2016 NCT02117479
Y-90 clivatuzumab Immunomedics Pancrit-1 Discontinued March 2016 NCT01956812
Algenpantucel-L NewLink Genetics Impress Failed NCT01072981

And a win in Pillar seems unlikely. In the Impress study algenpantucel-L did not achieve its primary goal of improving overall survival. In fact, median survival was longer in the placebo group, at 30.4 months, than in the treatment group, at 27.3 months. NewLink’s stock opened down 33% today.

Algenpantucel-L is no doubt facing a downgrade now – it had been forecast to become the biggest-selling pancreatic cancer drug by 2022, according to EvaluatePharma sellside consensus.

There are several other agents in phase III, but most are not set to report results until 2017. Next up should be Gilead’s momelotinib, but hopes are not high as it is a Jak inhibitor like Jakafi.

Past failures do not seem to be putting companies off the pancreatic cancer space, however. Recent entrants into pivotal trials include Halozyme’s PEGPH20, which is being investigated in combination with Celgene’s Abraxane and gemcitabine in previously untreated metastatic pancreatic cancer patients whose tumours have high levels of hyaluronan.

Meanwhile, AB Science has told EP Vantage that it has started a new European phase III study with its lead compound, Masican, in combination with gemcitabine, although this is not yet listed on clinicaltrials.gov.

Ongoing late-stage trials in pancreatic cancer
Project Company Study Trial ID Primary completion
Phase III
Momelotinib Gilead Sciences NCT02101021 July 2016
Algenpantucel-L NewLink Genetics Pillar NCT01956812 Dec 2016
Glufosfamide Eleison NCT01954992 May 2017
Nanoplatin/NC-6004 Orient/Nanocarrier NCT02043288 Jun 2017
Lynparza AstraZeneca Polo NCT02184195 Oct 2017
PEGPH20 Halozyme Halo-301 NCT02715804 Oct 2018
Gemcitabine +/- Masican AB Science N/A Unknown
Phase II/III
Imbruvica AbbVie/J&J  Resolve NCT02436668 Mar 2018

To contact the writer of this story email Madeleine Armstrong in London at madeleinea@epvantage.com or follow  @medtech_ma on Twitter

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