Novartis has published results from a clinical trial of Pear Therapeutics' new digital therapeutic for schizophrenia, and the results don't paint a rosy picture.

The single-blinded 112-person trial found no difference between the Pear app and a placebo app in any outcome measure, including the primary outcome measure of reducing schizophrenia symptoms. However, the trial did further establish the app's safety, as very few significant adverse effects were reported.

"In this study, PEAR-004 was not effective in the primary outcome of total PANSS scores compared with sham," investigators wrote in a results write-up published in a public Novartis database and first spotted by Exits and Outcomes. "The secondary and exploratory results also failed to find any noticeable benefits, except for possible temporary improvement of depressive symptoms."

While Pear's Thrive app delivered coping skills for schizophrenia symptoms, the placebo, or sham, app contained only a notification instructing participants to open the app each day and a timer counting down to the end of the treatment.

Speaking with MobiHealthNews, Pear CEO Corey McCann said the study was "disappointing," but also said there were "methodological issues" not mentioned in Novartis's publication.

"There was quite a broad statistical variability in how the individual studies implemented and directed patients to use both the 004 product as well as the placebo," McCann said. "We saw a number of sites directing patients to use 004 as well as the placebo outside of protocol directions. And lastly we observed differences between sites in how they interacted with patients and how they collected data. All of these things point to some of the difficulties of running trials for a new therapeutic modality."

According to McCann, this was the first study of its kind run by Novartis. McCann also mentioned that the trial did indicate high engagement rates with the app.

WHY IT MATTERS

Digital therapeutics are still in early days and to some extent are still proving themselves to the larger biopharma and health tech communities. As something of a standard-bearer for the space, a null result like this for Pear could shake some confidence in the burgeoning space. On the other hand, this is a single trial for a single therapeutic, and a number of other digital therapeutics from Pear and others have already posted strong clinical trial results.

An additional factor makes the results awkward for this particular therapeutic: it had already been rolled out to patients this past spring thanks to a loosening of FDA regulations during the COVID-19 emergency. 

McCann said this trial result will not impact that roll out, which constitutes a significantly upgraded version of the app that was the subject of the study with Novartis. On the contrary, he hopes that real-world data from that rollout could tell a different story from the Novartis study results.

Pear has also learned from the mistakes of this trial, McCann said, and has been working on better study designs for future investigations.

"We’ve built a fully-remote infrastructure so that we’re able to execute studies like that in a fully digital context," he said. "We believe that’s going to be a significant step forward in limiting that site-to-site variation that was seen in this study that may have called into question many of these results."

THE LARGER TREND

Novartis and Pear parted ways in late 2019 on their most high-profile collaboration around substance abuse recovery therapeutics reSET and reSET-O. At the time, the companies reiterated that the schizophrenia trial, along with a trial aimed at treating multiple sclerosis symptoms, were still being pursued under a separate collaboration with Novartis Institutes for BioMedical Research (NIBR). 

McCann says the two companies still have a strong relationship, citing Novartis's continuing participation in Pear's funding rounds.

Pear isn't the first digital therapeutics company to struggle with tackling schizophrenia. Proteus Digital Health, a digital therapeutics pioneer that filed for bankruptcy last year, made its big bet on schizophrenia when it partnered with Otsuka on a sensor-enabled version of Abilify. It's an area that's also proved difficult for traditional therapeutics.

ON THE RECORD

"I’d like to end by conveying what is a cautious optimism around digital therapeutics for schizophrenia," McCann said. "As you probably know this has been an incredibly difficult population for conventional therapeutics. There’s a whole history of clinical trial failures in the drug world and I think we’ve seen the beginning of some very interesting efficacy signals with digital therapeutics for this patient population and we’ll continue to push that forward."