Ver­tex may soon have three irons in the fire in its bid to re­peat the sci­en­tif­ic and fi­nan­cial suc­cess of its block­buster cys­tic fi­bro­sis med­i­cines.

The com­pa­ny on Thurs­day re­leased pos­i­tive re­sults from a pair of Phase II tri­als for its non-opi­oid pro­gram, an­nounc­ing that the ex­per­i­men­tal pill sig­nif­i­cant­ly re­duced pa­tients’ pain com­pared to place­bo in two post-op­er­a­tive tri­als. One tri­al looked at pa­tients who had just re­ceived a bunionec­to­my, the oth­er in pa­tients who re­ceived ab­domino­plas­ty — the med­ical term for a “tum­my tuck.”

Now, Ver­tex ex­ec­u­tives said they will push the drug in­to piv­otal tri­als lat­er this year. That will like­ly make it the third pro­gram in the Ver­tex pipeline to move in­to Phase III tri­als, af­ter its sick­le cell and be­ta-tha­lassemia gene ther­a­py and a treat­ment for ge­net­i­cal­ly dri­ven kid­ney dis­ease.

Al­though none have quite the sales po­ten­tial of CF, Ver­tex ar­gues they can each be cu­ra­tive or dis­ease-mod­i­fy­ing in ar­eas — like non-opi­oid pain re­lief — where progress has his­tor­i­cal­ly been slow.

“Our high ex­pec­ta­tions of achiev­ing ther­a­peu­tic pain con­trol … have been met with these re­sults from the two acute pain stud­ies,” said Ver­tex CMO Car­men Boz­ic. “The re­mark­able con­sis­ten­cy in the safe­ty, tol­er­a­bil­i­ty and ef­fi­ca­cy re­sults in these two stud­ies demon­strates the po­ten­tial of VX-548 to be a first-in-class non-opi­oid treat­ment for acute pain.”

Pain, how­ev­er, is a no­to­ri­ous­ly dif­fi­cult area for drug de­vel­op­ment, in part be­cause of the pro­found place­bo re­sponse many pa­tients can ex­pe­ri­ence. And the Phase II tri­als left at least some ques­tion about how well it will per­form in Phase III tri­als.

The com­pa­ny said that with­in 48 hours of surgery, bunionec­to­my pa­tients who re­ceived the high dose of the Ver­tex pill ex­pe­ri­enced sig­nif­i­cant­ly less pain than pa­tients who re­ceived place­bo. The same was true on tum­my tuck pa­tients in the high and mid-lev­el dose, when com­pared to tum­my tuck pa­tients on place­bo.

But one clear sign re­searchers look for in in­ter­pret­ing ear­ly stud­ies is whether there’s a dose re­sponse: Do pa­tients ex­pe­ri­ence more ben­e­fit as the dose in­creas­es?

In the bunionec­to­my tri­al, there wasn’t. Bunionec­to­my pa­tients who re­ceived the mid-lev­el dose ac­tu­al­ly ex­pe­ri­enced more pain than those on place­bo. And bunionec­to­my pa­tients who re­ceived the low­est dose saw some im­prove­ment over place­bo, al­though it was not sta­tis­ti­cal­ly sig­nif­i­cant.

At the same time, few com­pa­nies have two sta­tis­ti­cal­ly sig­nif­i­cant tri­als be­fore en­ter­ing Phase III tri­als. And it marks a mile­stone in a more than decades-long in­dus­try-wide ef­fort to de­vel­op al­ter­na­tives to opi­oids by tar­get­ing nerve re­cep­tors called Nav1.8 or Nav1.7 — a place where Pfiz­er, Roche and Bio­gen have all failed.

“While there are nu­ances that im­ply some out­stand­ing clin­i­cal risk (i.e. pain is hard, on­ly the high dose sep­a­rat­ed), ul­ti­mate­ly we feel con­fi­dent say­ing this mech­a­nism works,” Stifel’s Paul Mat­teis wrote in a note to in­vestors.

The EMA released updated recommendations today for the use of JAK inhibitors (JAKi) after reviewing data from several clinical trials that showed increased incidents of issues in certain patients who have rheumatoid arthritis and other risk factors.

The EMA noted malignancy, major adverse cardiovascular events (MACE), serious infections, venous thromboembolism (VTE) and mortality in some patients.