NEW YORK – Genetika+ is combining information on patients' symptoms, pharmacogenetics, and a so-called "brain-in-a-dish" functional testing model in the hopes of improving personalized drug prescribing for psychiatric conditions, with an initial focus on depression.
The Israeli company plans to launch its first drug-matching testing service for major depressive disorder, dubbed NeuroKaire, next year. Genetika+ hopes to promote NeuroKaire as a service doctors can use to improve patients' outcomes on antidepressants, reduce treatment-related side effects, and cut down on trial-and-error prescribing.
Millions of people across the globe struggle with major depressive disorder, and prevalence has increased with the COVID-19 pandemic. About one-third of patients see success with the first antidepressant they're prescribed, and patients try out up to four antidepressants before their symptoms subside, according to one study.
It can take four to six weeks to determine whether an antidepressant is working as expected, said Genetika+ Cofounder and CEO Talia Cohen Solal. If it isn't, the patient must return to their doctor and try a different drug. "That keeps going," over and over, until the patient finds a suitable medication, said Cohen Solal, who has a Ph.D. in neuroscience.
Genetika+ started prospective clinical trials to validate its antidepressant-matching platform earlier this year, and if all goes well, plans to begin offering commercial testing services by mid-2023, Cohen Solal said. The company, founded in 2018, received €17.5 million ($17.3 million) over the summer from the European Commission's European Innovation Council Accelerator to clinically validate and bring NeuroKaire to market. Before this, Genetika+ had raised $10 million in a Series A funding round.
The firm secured the CE mark for NeuroKaire in March. In the US, Genetika+ will offer NeuroKaire as a testing service through a CLIA-certified lab. The company plans to open its first US lab in New Jersey by year-end.
Physicians ordering Genetika+'s drug-matching services will collect blood samples from patients and send them to its clinical lab for testing. Based on analysis of the blood sample and information from patients, Genetika+ provides three reports to ordering physicians. The first test report details the pharmacogenetic markers impacting the patient's ability to metabolize various antidepressants.
The second report describes the patient's history of depression symptoms, based on an online questionnaire filled out by the patient. These patient-reported symptoms are also an important consideration when personalizing treatment decisions. If a patient is struggling to get out of bed, for example, a physician might want to avoid prescribing a drug that's known to cause drowsiness, Cohen Solal said.
For the third report, Genetika+ creates what it calls a "brain-in-a-dish." The company turns cells from a patient's blood sample into induced pluripotent stem (iPS) cells that it uses to create prefrontal cortical neurons — the kind of neurons affected in mental illness, Cohen Solal said. From there, Genetika+ exposes the neurons to various antidepressants to see which drugs or drug combinations have the "strongest impact on rescuing the connections," she said.
That provides a level of information beyond pharmacogenetic testing, according to the company, since it speaks to how the brain itself may respond to a given antidepressant.
All in all, it takes Genetika+ four to six weeks to return results to a physician. Daphna Laifenfeld, the company's cofounder and chief strategy officer, who also has a Ph.D. in neuroscience, acknowledged that the turnaround time for the firm's testing service is longer compared to that claimed by labs selling simpler pharmacogenetic tests, which can range from a few days to up to two weeks. Still, Laifenfeld maintained that Genetika+ is returning results in a time frame that will still be useful to patients.
Genetika+ sends its therapy recommendations — based on findings from the three reports — to the patient's physician as a PDF, which categorizes medications as green, orange, or red to delineate whether a particular drug is expected to be a good fit or should be avoided. If a medication is listed in the orange category, that means the drug might be contraindicated.
Researchers at Genetika+, including Laifenfeld and Cohen Solal, published a study in Translational Psychiatry last year describing the biomarkers they've identified in iPS cells that are associated with patients' responses to antidepressants, including synaptic connectivity, morphology changes, and varying gene expression.
So far, Genetika+ has validated its platform for 35 drugs covering the five major classes of antidepressants, and the company plans to add more, Cohen Solal said. The team is actively working to add an indication for matching schizophrenia patients to the right drugs and eventually wants to expand into attention deficit hyperactivity disorder and bipolar disorder.
"We consider ourselves the 'precision medicine for the brain' platform," Cohen Solal said.
Precision prescribing for antidepressants is an active area for pharmacogenomics testing firms, even though not all physicians are convinced of their utility and some want more evidence that testing improves patients' outcomes.
Treatment for major depressive disorder varies by patient, but might involve antidepressants and psychotherapy, said Chang-Gyu Hahn, a psychiatrist and a principal investigator on the research team at Philadelphia-based Thomas Jefferson University that's participating in a trial with Genetika+. The team is enrolling patients with major depressive disorder who have a known history of responsiveness or resistance to certain antidepressants.
If a patient doesn't respond to the first antidepressant they try, such as a selective serotonin reuptake inhibitor, the evidence available today isn't very instructive on what to do next, Hahn said. He's interested in whether Genetika+'s approach will provide information that helps to navigate such complexity and understand why people respond to different antidepressants.
Hahn is curious to what extent Genetika+'s model will strengthen the predictive power to identify the right depression treatments for patients beyond typical pharmacogenetic testing. "It will be wonderful to see how this integrative approach could serve to predict one's clinical responsiveness to antidepressants and ultimately help patients who suffer from depression," he said.
While Genetika+'s approach is more extensive than pharmacogenomic testing alone — and thus may take more time and have higher costs — that's not necessarily a downside if the test succeeds in improving patient care, he said.
If Genetika+ is successful in commercializing NeuroKaire, it plans to market the test to physicians prescribing antidepressants, such as psychiatrists and general practitioners. The company's cofounders expect doctors could submit for insurance coverage using existing CPT codes for pharmacogenetics testing, since their product incorporates pharmacogenetics. There could be a copay of up to $300, according to Cohen Solal.
Genetika+ is also striking partnerships with pharmaceutical firms, a business that Cohen Solal expects to contribute up to half of the company's revenue. She likened the business model to Foundation Medicine, a developer of cancer tumor profiling assays that also partners with drugmakers to identify best responders to their treatments and stratify patients in drug trials. Foundation Medicine, founded in 2010 and since acquired by Roche, has partnered with more than 65 biopharma partners, according to its website.
Pharmaceutical companies can use Genetika+'s platform and biobank of de-identified patient data to study new antidepressants. Cohen Solal said there's also an opportunity for pharma companies with failed investigational antidepressants to revive those programs in more specific patient subsets, for example. Genetika+ also supports pharmaceutical companies to identify clinical trial candidates, stratify patients, and advance companion diagnostics.
That could prove helpful as the company expands beyond major depressive disorder and into diseases like Alzheimer's and Parkinson's — conditions where patients don't have many treatment options to choose from.
"We want the patient to get the right drug for them, but it would be even better if there were even better drugs on the market, as well," Cohen Solal said.