Therapy Focus - Against The Odds, Cancer Vaccines Plough On

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Includes: AGEN, ARGS, BAVN, BVNKF, BVNRY, NWBO
by: EP Vantage

In spite of a near-100% track record of failure, and in the face of overwhelming scientific rationale to the contrary, late-stage development of therapeutic cancer vaccines continues. For some biotechs these troubled assets even represent a fundamental investment case.

Yet two more flops, in the form of Argos Therapeutics’ (OTC:ARGS) long-running Adapt study of rocapuldencel-T and an NIH-sponsored trial of Agenus’ (NASDAQ:AGEN) Prophage G-200, have just joined the growing list of cancer vaccine failures. This comes on the heels of a terrible year for this type of approach, which could next be tested by Bavarian Nordic (BAVN) (OTCPK:BVNKF) (OTCPK:BVNRY), a group that remains dependent on vanishing odds of success from its pivotal Prostvac study (see table below).

Bavarian recently said patients in the Prospect trial of Prostvac in prostate cancer were living longer than expected, which would delay results from the study from early 2017 to the second half of this year. The group optimistically opined that this “could ... be indicative of a therapeutic effect of Prostvac”.

This rose-tinted view ignored the other possibility – far more likely, based on historical precedent of delays to event-driven oncology trials – that all patients, including those on placebo, were living longer.

Skepticism

A recent increase in announcements about Bavarian’s RSV programcould hint at subtle moves to take attention away from Prostvac. It might be that earlier futility analyses set particularly high failure criteria, and having seen the blended, blinded survival curves from Prospect Bavarian can see that probability of success is tiny.

If chances of Prostvac giving a positive readout are slim, this is nothing compared with the possible next phase III cancer vaccine trial to yield data – Northwest Biotherapeutics’ (OTC:NWBO) study of DXVax-L in glioblastoma.

This trial has taken an inordinate amount of time, having started over 10 years ago, and was put on US clinical hold for undisclosed reasons in late 2015. Northwest recently said the hold had been lifted, and that it would analyse the dataset as it stands – with only 331 of a planned 348 patients recruited.

The group claims to have reached the intended number of disease progressions, the primary endpoint, but wants to wait for 233 deaths to be able to read out the important secondary overall survival endpoint. Thus investors have months more to wait, with the stock now languishing on the OTC bulletin board.

Seletced late-stage cancer vaccine trials

Company

Project

Study

Indication

Trial ID

Data

Bavarian Nordic/BMS

Prostvac

Prospect

Prostate cancer

NCT01322490

H2 2017

Northwest Biotherapeutics

DCVax-L

Glioblastoma multiforme

NCT00045968

H2 2017*

Sotio

Stapuldencel-T

Viable

Prostate cancer

NCT02111577

Dec 2017

Advantagene

ProstAtak

Ulyssses

Active surveillance for prostate cancer

NCT02768363

Dec 2017

Gradalis

Gemogenovatucel-T

Vital

1st-line ovarian cancer maintennance

NCT02346747

Dec 2017

Gradalis

Vigil

Triple-negative breast cancer

NCT02725489

May 2018

OSE Pharma

Tedopi

Atalante-1

2nd & 3rd-line NSCLC

NCT02654587

"Late 2018"

Tessa Therapeutics

TT10: EB-VST

Nasopharyngeal carcinoma

NCT02578641

Dec 2018

Immunocellular Therapeutics

ICT-107

Glioblastoma multiforme

NCT02546102

Dec 2019

Advantagene

ProstAtak

Adjuvant to RT in localised prostate cancer

NCT01436968

Dec 2019

Vaccinogen

OncoVAX

Adjuvant colorectal cancer

NCT02448173

Jul 2020

Bioven

EGF-PTI

Biomarker-positive, EGFR wild type NSCLC

NCT02187367

Feb 2020

Note: *At Feb 2017 company is waiting "several months" for desired number of events under new analysis plan.

Like Sanpower's Provenge, DCVax-L is an autologous product, whereas Prostvac is a subcutaneously injected virus vector expressing PSA, intended to lyse tumour cells and release antigens for presentation to the immune system. DCVax-L comprises autologous dendritic cells exposed to lysate taken from the tumor.

The scientific principle is similar in that both approaches aim to raise an immune response from existing T cells – a fundamental flaw of cancer vaccines. The immune system is unable ordinarily to target the desired antigens largely because it does not recognize them as foreign, so just presenting it with those same antigens might not be enough.

Cancer vaccines given as monotherapy at best stimulate existing, low-affinity T cells, a theory that likely explains their poor success rate. Argos added to the list last week, prompting a 75% share price crash, while Agenus lost 16% on the failure of what is no longer even an important pipeline asset.

Yet at the same time Patrick Soon-Shiong, founder of the Nantworks network of companies, spoke of launching a new cancer vaccine venture. And two cancer vaccines, Advantagene’s ProstAtak and Bioven’s EGF-PTI, have recently started new late-stage studies.

True, sooner or later the industry will see a cancer vaccine success, though this will likely need to involve an additional element, such as combination with a checkpoint-blocking MAb or with depletion of T regulatory cells. In the meantime there are likely to be plenty more disappointments.

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