New study ques­tions the need for 12 years of mar­ket ex­clu­siv­i­ty for bi­o­log­ics

The lengthy pre­clin­i­cal and clin­i­cal de­vel­op­ment nec­es­sary to bring a bi­o­log­ic to mar­ket has of­ten been cit­ed as one of the cen­tral rea­sons why bi­o­log­ics de­serve 12 years of mar­ket ex­clu­siv­i­ty, or about five years more ex­clu­siv­i­ty than their small mol­e­cule coun­ter­parts.

But a new study pub­lished Tues­day in Na­ture Biotech­nol­o­gy shows that the de­vel­op­ment time of a new bi­o­log­ic is gen­er­al­ly about the same as the de­vel­op­ment time of a small mol­e­cule drug.

The au­thors from the Pro­gram On Reg­u­la­tion, Ther­a­peu­tics, And Law (POR­TAL), Di­vi­sion of Phar­ma­coepi­demi­ol­o­gy and Phar­ma­coeco­nom­ics, De­part­ment of Med­i­cine, Brigham and Women’s Hos­pi­tal and Har­vard Med­ical School, note that “al­though bi­o­log­ics are of­ten thought to be more time-con­sum­ing to de­vel­op than small-mol­e­cule drugs, de­vel­op­ment times for bi­o­log­ics are sim­i­lar to, or pos­si­bly some­what short­er than, for small-mol­e­cule drugs.”

The study found that of the 275 new drugs ap­proved by the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) be­tween 2007 and 2016 (77% were small-mol­e­cule drugs and 23% were bi­o­log­ics), me­di­an to­tal de­vel­op­ment times—from first patent fil­ing to FDA ap­proval—were about 12 years for both types of prod­ucts.

Reed Beall Twit­ter

First au­thor Reed Beall, as­sis­tant pro­fes­sor with the Uni­ver­si­ty of Cal­gary, ex­plained to Fo­cus: “The main ra­tio­nales giv­en aca­d­e­m­ic de­bate around this is­sue of longer ex­clu­siv­i­ties has been that (#1) bi­o­log­ics are es­pe­cial­ly cost­ly in term of time/com­plex­i­ty/etc. to de­vel­op and man­u­fac­ture; and (#2) patents will not pro­vide ad­e­quate pro­tec­tion for a long enough ex­clu­siv­i­ty pe­ri­ods to re­coup in­vest­ments and prof­it.”

“We know now in hind­sight that #2 is like­ly un­ground­ed,” Beall said, point­ing to mul­ti­ple bi­o­log­ics that have staved off biosim­i­lar com­pe­ti­tion in the US de­spite be­ing on the mar­ket for more than 12 years. And this lat­est study shows how the tim­ing of de­vel­op­ment is not dif­fer­ent be­tween bi­o­log­ics and small-mol­e­cule drugs.

“As the tech sur­round­ing bi­o­log­ics is new­er, it’s nat­ur­al to ex­pect that get­ting off the ground will be dif­fi­cult in the be­gin­ning and will even­tu­al­ly be­come more ef­fi­cient. How­ev­er, if pol­i­cy sys­tem­at­i­cal­ly gives bet­ter mar­ket pro­tec­tions for bi­o­log­ics in the long term, it may in­cen­tivize in­vest­ment in the de­vel­op­ment of bi­o­log­ics over small-mol­e­cule drug, even though there’s no ob­vi­ous rea­son why we should pre­fer larg­er mol­e­cules to small ones. Now that the sci­ence is more ma­ture, it may be time to re­vis­it the da­ta and poli­cies sur­round­ing longer bi­o­log­ic ex­clu­siv­i­ties and pric­ing,” Beall said.

The study al­so notes how guar­an­teed ex­clu­siv­i­ty pe­ri­ods for bi­o­log­ics are short­er in oth­er, sim­i­lar coun­tries.

“For both bi­o­log­ics and small-mol­e­cule drugs, the Eu­ro­pean Union pro­vides 10 years of ex­clu­siv­i­ty, and Aus­tralia and New Zealand pro­vide 5 years of ex­clu­siv­i­ty. By con­trast, the Unit­ed States pro­vides 5 years of guar­an­teed ex­clu­siv­i­ty for small mol­e­cules that are new chem­i­cal en­ti­ties, al­though in prac­tice this ex­clu­siv­i­ty pro­vides clos­er to 7 years of mar­ket pro­tec­tion for small mol­e­cules be­cause the FDA can­not be­gin re­view­ing ap­pli­ca­tions from gener­ic com­peti­tors un­til the 5 years of da­ta ex­clu­siv­i­ty have ex­pired. This dis­par­i­ty in ex­clu­siv­i­ty in the Unit­ed States—12 years for bi­o­log­ics ver­sus rough­ly 7 years for small mol­e­cules—may in­cen­tivize in­vest­ment in the de­vel­op­ment of bi­o­log­ics over small-mol­e­cule drugs,” the study says.

But Beall al­so notes lim­i­ta­tions of the study, such as that it on­ly con­sid­ered drugs ap­proved by CDER, and did not in­clude prod­ucts that failed at some point dur­ing the de­vel­op­ment process or the rel­a­tive­ly small­er num­ber of prod­ucts ap­proved by the FDA’s Cen­ter for Bi­o­log­ics Eval­u­a­tion Re­search.

The study fol­lows a pol­i­cy pro­pos­al from Pew Health in 2017, which al­so sug­gest­ed re­duc­ing the ex­clu­siv­i­ty pe­ri­od for bi­o­log­ics, not­ing that the costs to de­vel­op bi­o­log­ics and small-mol­e­cule drugs are sim­i­lar.


First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

So­cial im­age: Shut­ter­stock


Zachary Brennan

managing editor, RAPS

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