Sci­pher Med­i­cine trans­lates com­plex bi­ol­o­gy to pre­dict bet­ter out­comes

Re­searchers at Sci­pher Med­i­cine have com­bined pro­pri­etary da­ta and ar­ti­fi­cial in­tel­li­gence to pre­dict a pa­tient’s re­sponse to cost­ly bi­o­log­ics. Sla­va Ak­maev, Ph.D., Sci­pher Chief Tech­nol­o­gy Of­fi­cer and Head of Ther­a­peu­tics de­scribes the im­pli­ca­tions of their new study, Net­work-004 that demon­strates the abil­i­ty of Prism­RA® to iden­ti­fy an­ti-tu­mor necro­sis fac­tor in­hibitor (TN­Fi) ther­a­py non-re­spon­ders in both naïve and TN­Fi ex­posed pa­tient pop­u­la­tions.

Dr. Ak­maev, how does Prism­RA match pa­tients with the best pos­si­ble med­i­cine?

Prism­RA is a mol­e­c­u­lar test that lever­ages pro­pri­etary da­ta to de­tect in­ad­e­quate re­spon­ders to tu­mor necro­sis fac­tor in­hibitor (TN­Fi) ther­a­py in mod­er­ate or high dis­ease rheuma­toid arthri­tis (RA). This is im­por­tant be­cause the an­ti-TN­Fs are the most com­mon­ly pre­scribed first line tar­get­ed ther­a­py in RA. The test was built around de­tect­ing po­ten­tial non-re­sponse in these pa­tients ini­ti­at­ing their first bi­o­log­ic.

Our lat­est pub­li­ca­tion, Co­hen et al., re­veals that Prism­RA can be used to test re­sponse to an­ti-TN­Fs not on­ly in treat­ment naïve pa­tients, but al­so TN­Fi-ex­posed pa­tients. The study fo­cused on pa­tients who failed their con­ven­tion­al sD­MARD ther­a­py and were con­sid­er­ing get­ting on the an­ti-TNF drugs, or small mol­e­cule tar­get­ed ther­a­py, such as JAK in­hibitors. We val­i­dat­ed Prism­RA in four pa­tient co­horts in­clud­ing a clin­i­cal ob­ser­va­tion­al study per­formed in mul­ti­ple sites across the Unit­ed States.

Imag­ine a pa­tient who start­ed a TN­Fi a few months ago and who may now be at the point where they’re try­ing to eval­u­ate and make the de­ci­sion whether to con­tin­ue their cur­rent an­ti-TNF course or switch to a dif­fer­ent ther­a­py. This is where the Prism­RA is ex­treme­ly use­ful. Pa­tients can take the test and un­der­stand if the an­ti-TN­Fs are like­ly to im­prove their dis­ease state. Prism­RA can help to guide that de­ci­sion by cal­cu­lat­ing a score to in­di­cate whether the pa­tient is un­like­ly to re­spond to the treat­ment in a mean­ing­ful way. We found in our Net­work-004 re­search that the test has sta­tis­ti­cal pow­er to pre­dict their six months out­comes.

What per­cent­age of pa­tients on an­ti-TNF would ben­e­fit from a switch?

RA pa­tients be­come re­frac­to­ry to their treat­ments af­ter a cer­tain pe­ri­od of time. This could hap­pen be­cause they de­vel­op an­ti­bod­ies to the drug or be­cause their cell mol­e­c­u­lar make-up changes. Prism­RA makes it pos­si­ble to look at the mol­e­c­u­lar pro­file and un­der­stand where the pa­tient is as it re­lates to their re­sponse to treat­ment.

In the­o­ry, clin­i­cal use of Prism­RA can in­crease re­sponse rates to tar­get­ed ther­a­pies by 40% by the ACR50 met­ric. That trans­lates to 12 ad­di­tion­al pa­tients achiev­ing ACR50 re­sponse in 6 months out of a 100. We are in the mid­dle of con­duct­ing a num­ber of clin­i­cal util­i­ty and RWE stud­ies that will look in­to it in more de­tail.

Achiev­ing re­mis­sion ear­li­er has huge down­stream ef­fects or dis­ease, right?

Achiev­ing re­mis­sion with a first line treat­ment may po­ten­tial­ly al­low pa­tients to man­age the dis­ease bet­ter and main­tain their cur­rent lifestyle, un­for­tu­nate­ly, there is no cure for RA at present. We know if the first tar­get­ed ther­a­py is not cor­rect­ly se­lect­ed, pa­tients will ex­pe­ri­ence dis­ease pro­gres­sion and ex­pe­ri­ence mol­e­c­u­lar shift such that, even when they get on the right ther­a­py, the re­sponse rates may be low­er. More­over, the analy­sis that we’ve per­formed on pub­lished da­ta com­par­ing first-line ther­a­py re­sponse to re­sponse to sec­ond-line or third-line ther­a­py in­di­cates that the pa­tient re­sponse to the cor­rect first-line ther­a­py is great­ly en­hanced. We thus be­lieve that pa­tients who can make that switch ear­li­er will have a com­plete­ly dif­fer­ent dis­ease tra­jec­to­ry.

Is this type of pre­ci­sion med­i­cine nov­el for rheuma­tol­ogy?

That’s a great ques­tion be­cause, in­ter­est­ing­ly enough, while pre­ci­sion med­i­cine in on­col­o­gy is com­mon­place, it is new in rheuma­tol­ogy. As ev­i­dence of this, the just re­leased Amer­i­can Col­lege of Rheuma­tol­ogy (ACR) guide­lines had pre­ci­sion med­i­cine out of scope.

Prism­RA is the first pre­dic­tive test in rheuma­toid arthri­tis. We are de­vel­op­ing this mar­ket and ed­u­cat­ing rheuma­tol­o­gists and the com­mu­ni­ty about use of pre­ci­sion med­i­cine in clin­i­cal prac­tice. Sci­pher is trail­blaz­ing this space and we ex­pect to see more at­ten­tion paid to pre­dic­tive di­ag­nos­tics in RA in the years to come.

How do you see pre­ci­sion med­i­cine af­fect­ing the fu­ture of rheuma­tol­ogy?

As has hap­pened with on­col­o­gy, I think a fo­cus on pre­ci­sion med­i­cine may change the way we think of rheumat­ic dis­eases. I think in the case of rheuma­toid arthri­tis and oth­er au­toim­mune dis­eases, such as in­flam­ma­to­ry bow­el dis­ease and pso­ri­at­ic arthri­tis, there’s prob­a­bly a num­ber of pa­tient groups that share mol­e­c­u­lar mech­a­nisms that dri­ve dis­ease. As with on­col­o­gy, we will be­gin in rheuma­tol­ogy to look at mol­e­c­u­lar me­chan­ics and mol­e­c­u­lar dys­reg­u­la­tion to iden­ti­fy phe­no­types of pa­tients more like­ly to re­spond to cer­tain ther­a­peu­tic in­ter­ven­tions.