Glax­o­SmithK­line's Benlysta earns first FDA ap­proval for lu­pus nephri­tis as com­peti­tors wait in the wings

When Glax­o­SmithK­line earned its first ap­provals back in 2011 for Benlysta, it promised reg­u­la­tors it would keep the ball rolling in its pur­suit of lu­pus nephri­tis, a se­vere form of the au­toim­mune dis­ease that can cause re­nal fail­ure. Now, near­ly a decade af­ter the bi­o­log­ic first hit the mar­ket, GSK has made good on that promise.

The FDA on Thurs­day ap­proved in­tra­venous and sub­cu­ta­neous Benlysta to treat LN, mak­ing it the first ther­a­py ever ap­proved for that in­di­ca­tion.

The agency based its re­view on re­sults from the Phase III Bliss-LN study, which showed 43% of lu­pus nephri­tis pa­tients in the Benlysta plus stan­dard-of-care arm achieved pri­ma­ry ef­fi­ca­cy re­nal re­sponse — a mea­sure of kid­ney func­tion — com­pared with 32% of pa­tients in the place­bo group. Pa­tients on Benlysta al­so post­ed sig­nif­i­cant­ly high­er re­sponse in sec­ondary end­points, in­clud­ing time to death or a kid­ney-re­lat­ed com­pli­ca­tion.

Lu­pus nephri­tis is a se­vere form of sys­temic lu­pus ery­the­mato­sus that can cause late-stage re­nal fail­ure and re­quire dial­y­sis or kid­ney re­place­ment in the worst cas­es. Hav­ing a ther­a­py on the mar­ket that can cut in­to the de­mand for those sur­gi­cal pro­ce­dures is a big win for the 60% of 328,000 se­vere US lu­pus pa­tients suf­fer­ing from lu­pus nephri­tis each year, GSK said.

“In the four decades I have been car­ing for peo­ple with lu­pus, we have not been able to achieve re­mis­sion in more than just one-third of pa­tients with lu­pus nephri­tis and, de­spite all of our ef­forts, 10% to 30% of pa­tients with lu­pus kid­ney dis­ease still progress to end-stage kid­ney dis­ease,” said Richard Fu­rie, chief of the di­vi­sion of rheuma­tol­ogy and pro­fes­sor at the Fe­in­stein In­sti­tutes for Med­ical Re­search at North­well Health and lead in­ves­ti­ga­tor of the Bliss study, in a re­lease. “There­fore, it is grat­i­fy­ing to see the re­wards of decades of re­search.”

Ex­pect­ing an uptick in de­mand for Benlysta and look­ing to fi­nal­ly crack in­to block­buster ter­ri­to­ry, GSK has been quick­ly ex­pand­ing its man­u­fac­tur­ing ca­pac­i­ty to dri­ve sup­ply world­wide.

In Oc­to­ber 2019, GSK un­veiled plans to in­fuse $139 mil­lion plant at its Rockville, MD site to add ca­pac­i­ty for Benlysta. The drug­mak­er chose to retro­fit an ex­ist­ing build­ing at the Mary­land site, where it al­ready had ex­per­tise in pro­duc­ing the in­ject­ed or in­fused drug. The in­vest­ment was used to pay for the de­mo­li­tion of ex­ist­ing suites and the en­gi­neer­ing, in­stal­la­tion and val­i­da­tion of new equip­ment.

Then, in May of this year, the British phar­ma worked out a $231 mil­lion deal with CD­MO Sam­sung Bi­o­log­ics to out­source pro­duc­tion of its bi­o­log­ic prod­ucts, in­clud­ing Benlysta, over the next eight years. The deal will ini­tial­ly cov­er Benlysta, with the first com­mer­cial sup­ply ex­pect­ed in 2022. Benlysta gen­er­at­ed sales of $747 mil­lion in 2019, prop­ping up an oth­er­wise mea­ger bi­o­log­ics port­fo­lio for the Big Phar­ma. The drug pulled in $252 mil­lion in sales in the third quar­ter, putting it on pace to hit the block­buster mark.

Mean­while, chal­lengers from Roche and Au­rinia are rac­ing to­ward the mar­ket in lu­pus, pos­ing an ex­is­ten­tial chal­lenge to Benlysta’s hold on the hard-to-win mar­ket.

In June 2019, Roche post­ed Phase II da­ta show­ing blood can­cer med Gazy­va on top of stan­dard-of-care ther­a­py best­ed stan­dard of care alone in achiev­ing com­plete re­nal re­sponse for lu­pus nephri­tis pa­tients. The drug earned the FDA’s break­through tag back in Sep­tem­ber 2019. An­oth­er chal­lenger, Au­rinia’s late-stage lu­pus nephri­tis can­di­date vo­closporin, faces an FDA re­view date of Jan. 22, mak­ing it the ear­li­est po­ten­tial chal­lenger to GSK’s newest in­di­ca­tion.

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Pascal Soriot, AP

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Anthony Fauci, NIAID director (AP Images)

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