For the first time, the FDA will con­sid­er whether to ap­prove a trio of drugs for tiny pa­tient pop­u­la­tions based on tri­als that are us­ing bi­o­log­i­cal sig­nals as out­comes, rather than a place­bo com­par­i­son.

It’s a cru­cial mo­ment not just for the three com­pa­nies and the drugs, but al­so a chance to re­move what’s long been seen as a ma­jor road­block to de­vel­op­ing treat­ments for ul­tra-rare dis­ease pop­u­la­tions. It al­so comes as the FDA has sig­naled an open­ness to lean­ing on bio­mark­ers, which would let com­pa­nies prove treat­ments work with a sin­gle clin­i­cal tri­al and lat­er con­fir­ma­to­ry ev­i­dence.

“From a broad­er rare dis­ease per­spec­tive, this would be some­thing that, if I was look­ing at oth­er drugs, it would serve as fa­vor­able prece­dent,” Stifel an­a­lyst Paul Mat­teis said.

GH Re­search has shared com­pelling da­ta in peo­ple with a tra­di­tion­al­ly chal­leng­ing form of de­pres­sion dosed with its psy­che­del­ic can­di­date, de­spite the drug be­ing un­der a clin­i­cal hold in the US that dates back two years.

The com­pa­ny’s as­set, dubbed GH001, pro­duced an av­er­age 15.2-point re­duc­tion in a rat­ing scale for de­pres­sion symp­toms called the MADRS at eight days com­pared with a 0.3-point in­crease for place­bo. The Phase 2b tri­al en­rolled 81 pa­tients in Eu­rope with treat­ment-re­sis­tant de­pres­sion (TRD), with a rough­ly even split be­tween those giv­en treat­ment and those as­signed place­bo.

The tri­al al­so met all its sec­ondary end­points, ac­cord­ing to a com­pa­ny re­lease pub­lished Mon­day. GH’s share price GHRS was up around 80% at mar­ket open.

Al­giax Phar­ma­ceu­ti­cals’ non-opi­oid can­di­date has achieved “clin­i­cal­ly mean­ing­ful” pain re­duc­tion in a mid-stage tri­al of peo­ple with pe­riph­er­al post-sur­gi­cal neu­ro­path­ic pain, mark­ing an­oth­er suc­cess in an area that has re­cent­ly been gain­ing mo­men­tum de­spite a chal­leng­ing his­to­ry.

More than a quar­ter of pa­tients treat­ed with the Ger­man biotech’s GABAA-re­cep­tor mod­u­la­tor, dubbed AP-325, saw at least 50% pain re­duc­tion com­pared with 11% of place­bo pa­tients, ac­cord­ing to da­ta shared with End­points News. The Phase 2a study en­rolled al­most 100 pa­tients across 27 tri­al sites in Ger­many, Spain, the Czech Re­pub­lic, Bel­gium and France.

Fur­ther, over half the pa­tients in the treat­ment co­hort didn’t need any res­cue pain med­ica­tion ver­sus 21% of place­bo pa­tients. AP-325 was well-tol­er­at­ed with no se­ri­ous ad­verse events ob­served and ze­ro cen­tral ner­vous sys­tem symp­toms such as drowsi­ness or se­da­tion, chief sci­en­tif­ic of­fi­cer Gui­do Koop­mans told End­points in an in­ter­view.

Ra­dio­phar­ma­ceu­ti­cals biotech Ad­van­Cell has pulled to­geth­er a $112 mil­lion Se­ries C about two years af­ter its much small­er Se­ries B of $12 mil­lion.

Since that fi­nanc­ing took place in 2022, the ra­dio­phar­ma­ceu­ti­cals mar­ket has ex­plod­ed. Though on­ly a few agents are ap­proved, dozens of biotech star­tups have come to the fore. No­var­tis, Eli Lil­ly, Bris­tol My­ers Squibb, As­traZeneca and oth­er large drug­mak­ers have put down bil­lions of dol­lars to ac­quire those com­pa­nies. And mul­ti­ple ra­dio­phar­ma star­tups have al­so at­tract­ed col­lab­o­ra­tions or li­cens­ing deals.

Ad­van­Cell it­self teamed up with In­di­anapo­lis-based Point Bio­phar­ma in 2023 for undis­closed terms. Lil­ly bought Point for more than $1 bil­lion in Oc­to­ber 2023.