What's changed about rare dis­ease med­i­cine

(This is our lat­est is­sue of Post-Hoc, a dis­patch of analy­sis and per­spec­tives from the End­points news­room. To get it di­rect­ly in your in­box, you can mod­i­fy your sub­scrip­tion pref­er­ences here in the “pref­er­ences” tab.)

Last week, End­points News pub­lished my in-depth sto­ry about teenag­er Con­nor Dal­by, who for near­ly all of his life has suf­fered con­stant seizures. In March, Con­nor re­ceived the first dose of a be­spoke treat­ment for his one-of-a-kind ge­net­ic dis­ease.

I’ve been fol­low­ing Con­nor and his fam­i­ly for more than three years. And dur­ing that time, a huge amount has changed in the world of ul­tra-rare dis­eases, both with the re­searchers try­ing to help pa­tients, and with the reg­u­la­tors over­see­ing it all.

In some ways, it’s got­ten much more dif­fi­cult to de­vel­op drugs, par­tic­u­lar­ly for con­di­tions that are es­pe­cial­ly rare. A wider in­dus­try down­turn has led many com­pa­nies to aban­don promis­ing ther­a­peu­tics.

But I got a first­hand look at sci­en­tif­ic ad­vances that spell re­al promise. The n-Lorem Foun­da­tion seized on an­ti­sense oligonu­cleotides — a cus­tomiz­able drug tech­nol­o­gy — to de­vel­op 17 med­i­cines, in­clud­ing one for Con­nor’s unique case. The group even­tu­al­ly as­pires to treat thou­sands of pa­tients like him.

Whether n-Lorem will suc­ceed re­mains to be seen. But there’s now a wider con­ver­sa­tion go­ing on about how our sci­en­tif­ic, in­vest­ing and reg­u­la­to­ry sys­tems grap­ple with dis­eases and pa­tients who of­ten don’t fit our cur­rent con­structs. Last week, for ex­am­ple, No­bel Prize win­ner Jen­nifer Doud­na and oth­ers pub­lished a piece in Na­ture out­lin­ing a roadmap to slash the cost of cre­at­ing gene ther­a­pies.

Even if peo­ple like Doud­na can fig­ure out the eco­nom­ics, there are still ques­tions about whether the FDA can fig­ure out how to deal with an in­flux of these pro­grams. As part of my re­port­ing, I asked Pe­ter Marks, the FDA’s di­rec­tor of the Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search, about this. He point­ed to the agency’s ef­forts to de­vel­op a so-called plat­form pol­i­cy that could al­low drug de­vel­op­ers to si­mul­ta­ne­ous­ly tar­get mul­ti­ple dis­eases with­out re­do­ing crit­i­cal work.

“It could be some­thing that makes an un­at­trac­tive busi­ness propo­si­tion a more at­trac­tive one,” Marks said. (Af­ter our in­ter­view, Marks an­nounced an­oth­er FDA ini­tia­tive: a Rare Dis­ease In­no­va­tion Hub that aims to uni­fy the agency’s ap­proach to rare dis­ease med­i­cines.)

Marks is push­ing the FDA to­ward more reg­u­la­to­ry flex­i­bil­i­ty (though not with­out con­tro­ver­sy), just as groups like n-Lorem and oth­ers are try­ing to push ahead with tri­als, drugs and fund­ing mod­els. The prob­lems that have held back rare dis­ease med­i­cine won’t go away any­time soon. But there’s un­de­ni­able mo­men­tum to ad­dress them.

— Jared