The FDA on Mon­day said it up­dat­ed its rec­om­men­da­tions for the clin­i­cal de­vel­op­ment of new an­tibac­te­r­i­al drugs, and thanks to a new clutch of drugs, spon­sors will have to con­duct non­in­fe­ri­or­i­ty tri­als that in­clude sub­jects with in­fec­tions caused by cer­tain drug-re­sis­tant or­gan­isms be­cause an ef­fec­tive ac­tive con­trol can be pro­vid­ed.

The guid­ance, which has since been re­leased, builds on a 2017 doc­u­ment and spec­i­fies what non­in­fe­ri­or­i­ty tri­al de­signs may be used “with a wider NI mar­gin,” in­clud­ing cas­es in which the tri­al pop­u­la­tion is en­riched for sub­jects with in­fec­tions caused by cer­tain drug-re­sis­tant or­gan­isms, FDA said.

The fed­er­al agency said in the guid­ance that the ac­tive com­para­tor used to show non­in­fe­ri­or­i­ty should be ef­fec­tive for the pop­u­la­tion en­rolled in the clin­i­cal tri­al, fur­ther stat­ing that the pri­ma­ry analy­sis should ex­clude sub­jects with base­line pathogens re­sis­tant to the con­trol.

“A ran­dom­ized tri­al de­sign is need­ed be­cause both com­par­a­tive safe­ty and ef­fi­ca­cy eval­u­a­tions can be per­formed. The ran­dom­ized clin­i­cal tri­al da­ta can be sup­port­ed by con­fir­ma­to­ry ev­i­dence from non­clin­i­cal stud­ies demon­strat­ing the ac­tiv­i­ty of the in­ves­ti­ga­tion­al drug against re­sis­tant phe­no­types,” the guid­ance went on to say.

When draft­ing the guid­ance, an FDA spokesper­son told End­points News that FDA was con­sid­er­ing re­cent­ly ap­proved be­ta-lac­tam/be­ta-lac­ta­mase in­hibitor com­bi­na­tions that showed ex­tend­ed ac­tiv­i­ty against drug-re­sis­tant or­gan­isms, such as those that pro­duce car­bapen­e­mases.

Since 2017, about 12 new drugs won ap­proval in this space, show­ing ac­tiv­i­ty against treat­ment-re­sis­tant or­gan­isms — in­clud­ing drugs like TB Al­liance’s pre­tomanid, which got the thumbs up from the fed­er­al reg­u­la­tor for treat­ment-re­sis­tant tu­ber­cu­lo­sis ap­proved back in 2019. Oth­ers in­clude Achao­gen’s pla­zomicin, now known as Zem­dri, for com­pli­cat­ed uri­nary tract in­fec­tions in 2018 and No­var­tis spin­off Nabri­va’s lefa­mulin for pneu­mo­nia.

Yet as NIH re­searchers added in an ar­ti­cle they wrote in late 2019, that num­ber of drugs is not enough for the space.

The 2017-era guid­ance orig­i­nal­ly fo­cused on flex­i­bil­i­ty, with the agency say­ing that “it is ap­pro­pri­ate to ex­er­cise the broad­est flex­i­bil­i­ty in ap­ply­ing the statu­to­ry stan­dards, while pre­serv­ing ap­pro­pri­ate guar­an­tees for safe­ty and ef­fec­tive­ness.” It added that it rec­og­nized that physi­cians and pa­tients are “gen­er­al­ly will­ing to ac­cept greater risks or side ef­fects from drugs that treat life-threat­en­ing and se­vere­ly-de­bil­i­tat­ing ill­ness­es, than they would ac­cept from drugs that treat less se­ri­ous ill­ness­es.”

GSK has landed a new first from UNICEF — the first-ever contract for malaria vaccines, worth up to $170 million for 18 million vaccine doses distributed over the next three years.

The vaccine, known as Mosquirix or RTS,S, won WHO’s backing last October after a controversial start, but UNICEF said these doses will potentially save thousands of lives every year.

“We hope this is just the beginning,” Etleva Kadilli, director of UNICEF’s supply division, said. “Continued innovation is needed to develop new and next-generation vaccines to increase available supply, and enable a healthier vaccine market. This is a giant step forward in our collective efforts to save children’s lives and reduce the burden of malaria as part of wider malaria prevention and control programmes.”