Roche torches a mountain of biobucks, sweeping out a roster of drugs in the latest pipeline cleanup

While Roche $RHHBY posted its Q3 update on the numbers, highlighting the importance of its new blockbusters in replacing some aging franchises, the R&D group used the occasion to unceremoniously sweep out a roster of losers from the pipeline.

At the top of the list, Roche is dropping a Phase III program for Actemra as a treatment for systemic sclerosis. The move comes after researchers concluded last fall that the drug “is associated with benefits for skin fibrosis, lung fibrosis and physical function in patients with SSc but increased the risk for serious infections.”

Removed from their Phase II pipeline without explanation: RG6125, a Cadherin-11 mAb for rheumatoid arthritis.

The pharma player was angling for the big second-line therapy group for RA, for patients who fail on methotrexate and an anti-TNF-alpha drug. RG6125 was billed as the first antibody that targeted stromal cells, offering a shot at treating the disease without suppressing the immune system — something that has severe physical consequences for patients.

The drug started the Phase II about a year ago, and evidently has not performed well.

Six Phase I programs didn’t make it to the next level.

On the scrap heap this quarter (on page 49 of the review) you’ll find an antibody directed against the tyrosine kinase receptor colony stimulating factor 1 receptor that Roche had been developing in combination packages for solid tumors, a Nav 1.7 pain drug partnered with Xenon, another solid tumor program from Array, an asthma drug and a fibrosis therapy.

At the top of this list is RG7155, or emactuzumab, an antibody designed to block inflammation by inhibiting the binding of colony-stimulating factor-1 (CSF-1) to CSF1R.

There were two combos that didn’t make it out of early-stage testing:

  • RG7155 emactuzumab + Tecentriq for solid tumors
  • RG7155 emactuzumab + selicrelumab

The next drug works to stop DNA repair mechanisms, facilitating the death of cancer cells, much like PARP. In this case it’s a checkpoint kinase 1 inhibitor, targeting a key enzyme in assisting chemo.

  • RG7741 (GDC-0575) Chk1 inh – solid tumors

Way back in 2011 Genentech reportedly paid $28 million upfront to pick up the drug from Array. And the pact reportedly included some big milestones for the preclinical drug, even though Roche had another Chk1 — GDC-0425 (RG7602) — in the pipeline.

I asked Roche about these drugs and they replied:

Emactuzumab showed promising biological activity in a phase I study in solid tumours, as both a monotherapy and in combination with other therapies. It was then investigated in additional phase I/II studies, including in combination with Tecentriq in patients with advanced solid tumours. Results from this combination trial indicated the combination is not meaningfully better than Tecentriq alone in this patient population. As such, we are halting the development program for emactuzumab. In Aug 2018 the decision was made to discontinue futher development of emactuzumab.

As part of our commitment to follow the science, we also explored emactuzumab as a treatment for other indications including pigmented villonodular synovitis (PVNS), a rare joint disease that is caused by overexpression of CSF-1. While these indications are not aligned with our core business, we want to ensure patients may one day be able to benefit from emactuzumab and will consider out-licensing opportunities as appropriate.

As for RG6125 and RG7741: They “did not show the clinical benefit we expected and they were discontinued due to portfolio prioritization.”

Next up: A pain deal gone bad. RG6029 (Genentech’s GDC-0310) Nav 1.7 inhibitor for pain, which was being developed under a 7-year-old, $646 million deal with Xenon $XENE, is out the back door.  

Then there is RG7990 – a bispecific from NovImmune targeting IL13/IL17 for asthma.

And finally we have a drug they marked as out-licensed:

  • RG6069, an anti-fibrotic agent.

Failure, of course, is all part of R&D. Unfortunately, developers like Roche don’t like to provide details about what went wrong for its clinical drugs that flunk out.

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Sr. Manager, Regulatory Affairs, CMC
CytomX Therapeutics San Francisco, CA
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Catalytic Data Science Charleston, SC
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Flatiron Health New York City or San Francisco

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