NEW YORK (GenomeWeb) – About two years after launching, personalized medicine firm Pairnomix is beginning to collect the first data that demonstrates how its model for uncovering potential treatments via painstaking in vitro research into a patient's genomic variant can positively impact their health.
Though the data is anecdotal, the company has now made note of two different examples where patients appear to have benefitted when treated with off-label medications that were identified through this process of individualized drug screening.
Pairnomix's approach is akin to a pharmaceutical testing pipeline, but applied to an individual patient based on a particular genomic alteration that they carry, instead of for a more generalized population. This exhaustive process can include everything from basic functional genetics studies of a patient's mutation to in vitro screens of potentially active compounds.
The company is using these processes in studies funded by advocacy groups, with an initial focus on epilepsy, but it also offers this service commercially, although the expense involved means that the firm's business model is limited to wealthy families. Though the company hasn't disclosed prices, CEO Matt Fox has said that just to build cell lines and do its first characterization steps can cost $75,000 to $100,000 in some cases.
As a commercial prospect, making the case for such an expensive offering can't be easy. And eventually, Fox has said that he hopes that Pairnomix will be able to collect enough case results to be able to make a case for insurance coverage of its services that would expand access to more families. In either case, the company will likely need strong evidence that the benefit of what it is doing merits the costs.
In that vein, the company shared the first case report demonstrating its methodology at the end of 2016, in a poster at the annual meeting of the American Epilepsy Society. In that case, Pairnomix was able to identify a lead candidate therapy — amitriptyline — that isn't usually used to treat epilepsy. However, the doctor in question didn't prescribe that drug, so the firm wasn't able to collect data on how it's approach directly affected the patient's outcome.
However, since then another patient living outside the US who carries the same specific gain-of-function mutation in SCN8A has been treated with amitriptyline based on the company's findings.
Although Pairnomix has strict guidelines for communication of results only to the individual patient's physician, Fox has said that one way the impact of its results could be made useful to greater numbers of families is if they benefit others who carry the same alteration. In this case, the company was not working with this doctor, but its findings, as reported at AES, informed the choice to try the drug.
The data on the patient's response is limited so far, Fox cautioned, but it appears to support the results of Pairnomix's drug screen. Amitriptyline reduced the duration and intensity of the individual's seizures.
Interestingly, the doctor later stopped amitriptyline and tried a different anti-depressant, aripiprazole (Abilify), which Pairnomix's research suggested would not be effective. On that drug, the patient's seizures became more intense. And back on amitriptyline, they saw the initial benefit restored.
This "unintentional washout period," although still anecdotal, adds some weight to the likelihood that what the company is seeing in the context of this patient can be relied upon, Fox said this week.
In addition to the SCN8A case, Pairnomix has also been working with funding and other support from an advocacy group called KCNQ2 Cure Alliance.
The company presented new data from a case that was part of that effort at this year's AES meeting, where it reported that it was able to identify a number of drugs that mitigated the functional deficit conferred by a specific gain-of-function mutation in KCNQ2 — found in a child diagnosed with early infantile epileptic encephalopathy and global developmental delay.
This patient, who recently turned five, had a relatively low seizure burden, but suffered from neuromuscular and other issues. "She could sit upright in a chair at two, but then lost that, and now needs head and neck support in a wheelchair," Fox said.
Interestingly, the patient's KCNQ2 mutation is a gain-of-function variant, which is quite rare in the population of seizure sufferers in this genetic subset. So what Pairnomix was looking for in this case were drugs that limit that gain of function, a list of treatments which — because of the uniqueness of this type of a mutation — would be expected to be different than those that might work for the majority of KCNQ2 patients.
"We ran our screen, and we have about 1,400 drugs that are across all different mechanisms of action that we include," Fox said. "And among the many drugs which showed an effect on our model, the one that stood out for this specific mutation was paroxetine [GlaxoSmithKline's Paxil]."
"We're not aware of Paxil being used or indicated for epilepsy, and so we provided that information to the physician as we always do … and they ordered that drug from a compounding pharmacy in a liquid form," which the doctor started the patient on "well below recommended prescribing dosage," Fox added.
Again, Fox said, the evidence from this case is anecdotal, and doesn't represent a thorough scientific analysis, but the family reported that their child began to have improved sleep almost immediately, and has not suffered a seizure in the 5 months since beginning treatment.
Physical therapists have also noted dramatic improvement in the patient, who reportedly can sit up better, can lift her head, and can manipulate objects in ways she could not before.
The drug appears to still be well tolerated as the doctor has increased dosage each month, Fox added, and more recently the child has been weaned off of treatment with a more standard anti-epileptic drug with no ill effects so far.
According to Fox, Pairnomix is working on conducting and publishing more formalized, IRB-approved N-of-1 studies that will hopefully recapitulate the positive outcomes that it can only report on anecdotally at this point. The firm plans to begin that work next year.