Roche culls key phase 3 drug trials, including a cancer med and an autism 'breakthrough' therapy

As the first tranche of quarterly results starts coming through for Big Pharma, questions are naturally arising about the new threats from COVID-19, but Swiss major Roche is also sticking to the old playbook, quietly dumping trials of pipeline drugs.

In its financials this morning, Roche saw strong growth of 7% at constant exchange rates and kept its guidance for the year, despite what will be significant headwinds in 2020.

But it also had a big first-quarter clear-out, something of a tradition for pharmas, which includes two major late-stage experimental efforts, several meds in midstage testing and also a failed phase 2.

The first of the phase 3 drugs to be “removed,” according to its latest update, is its FDA breakthrough-tagged autism hopeful balovaptan (RG7314).

The drug aimed to treat autism by modulating the activity of vasopressin, a hormone that first emerged as a possible drug target in the disorder a few years ago. It blocks the activity of the V1a vasopressin receptor subtype and was given the FDA label back in 2018.

Vasopressin is a neuropeptide that helps neurons in the brain communicate with each other and seems to play a role in social bonding. In the case of autism, higher levels in the blood correlate with better social functioning in individuals.

A similar approach has been tried with oxytocin, another neuropeptide that was shown to enhance social functioning in a small study in children with autism reported in 2017 but has also failed other clinical trials. As with vasopressin, higher levels of oxytocin seem to be linked to higher functioning, so the team is selecting children with lower levels of the neuropeptide in additional studies.

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Roche’s approach was rather different, speculating that blocking the activity of the hormone at one receptor will help improve social functioning and avoid potential side effects of increasing vasopressin across the board, which some scientists believe could lead to increased aggression.

In a study in adult males with autism a few years back, balovaptan had showed a trend toward activity on social functioning scores but failed to reach statistical significance, though it was able to achieve a significant improvement on an adaptive behavior rating scale at higher doses.

Roche gave few details on the fate of the drug, except to say that a study is adults with autism was stopped in the first quarter “after a pre-planned futility analysis.”

The pharma industry has had a tough time trying to develop an effective treatment for autism, with a string of product failures in recent years; Novartis, Roche and Seaside Therapeutics are among those with defunct programs.

Roche has also “removed” idasanutlin (RG7388), an investigational MDM2 inhibitor, which was being tested for relapsed or refractory acute myeloid leukemia in phase 3. In its slides from the company’s financials, it marked a big red "X" next to the highly expected results from Mirros, a 440-patient trial of idasanutlin with chemo in relapsed/refractory patients.

According to a recent analysis from EvaluateVantage, “key to success could be idasanutlin's use in combination with Venclexta.” As of March, the trial was “Active, not recruiting,” according to

A phase 2 test of the med for a rare form of blood cancer called polycythemia vera was also cut.

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Further culled was a test for nemolizumab, a first-in-class investigational monoclonal antibody that blocks signaling of IL-31, which was being tested for pruritus (itching) in dialysis patients. It is a Galderma drug (and originally penned with Roche buyout Chugai) and is also being tested in atopic dermatitis.

Roche added that a phase 2 trial of its Prothena-partnered Parkinson’s hopeful prasinezumab, an anti-αSynuclein, “did not meet its primary objective, but shows signals of efficacy.” Roche is now “evaluating the data to determine next steps,” it said; part two of the trial is still ongoing.

The pharma also removed phase 2 drug basmisanil, a highly selective inverse agonist/negative allosteric modulator of α₅ subunit-containing GABAA receptors, which was working on the treatment of cognitive impairment associated with schizophrenia.