“Reg­u­la­tions have in­flu­enced evo­lu­tion of biosim­i­lars mar­ket”

BioSpectrum (Asia) - - Bio Content - Dr Charu Manak­tala MD, Head of Asia Pa­cific Biosim­i­lars Cen­ter of Ex­cel­lence at IQVIA

The biosim­i­lars space con­tin­ues to evolve rapidly and presents a num­ber of unique chal­lenges and fierce com­pe­ti­tion. There are many biosim­i­lars in de­vel­op­ment for some of the top-sell­ing bi­o­log­i­cals cre­at­ing an in­tense com­pe­ti­tion amongst the spon­sors, es­pe­cially those wish­ing to en­ter the western mar­kets. To avoid any de­lays, biotech com­pa­nies need solid clin­i­cal de­vel­op­ment plans built on the lat­est reg­u­la­tory guid­ance with in­ti­mate knowl­edge of the clin­i­cal trial land­scape. Re­cently, Priyanka Ba­j­pai from BioSpec­trum Asia spoke to Dr Charu Manak­tala MD, Head of Asia Pa­cific Biosim­i­lars Cen­ter of Ex­cel­lence at IQVIA on how com­pa­nies can de­sign their clin­i­cal de­vel­op­ment plans to meet the western reg­u­la­tors ex­pec­ta­tions. Dr Manak­tala has over 20 years of work ex­pe­ri­ence in the health­care and phar­ma­ceu­ti­cal in­dus­try and has worked in all stages of clin­i­cal drug de­vel­op­ment from Phase-I through com­mer­cial­iza­tion.

What is the fu­ture of biosim­i­lars?

The fu­ture of biosim­i­lars is bright – reg­u­la­tory path­ways are be­com­ing clearer and physi­cian ac­cep­tance is grow­ing.

For ex­am­ple, the reg­u­la­tory path­way for biosim­i­lars is well es­tab­lished in the In­ter­na­tional Con­fer­ence on Har­mo­niza­tion (ICH) re­gions and reg­u­la­tory re­quire­ments are be­com­ing more straight­for­ward. To date the Euro­pean Medicines Agency (EMA) has ap­proved 40 biosim­i­lars for 12 unique bi­o­log­i­cal tar­gets; the US FDA has ap­proved eight biosim­i­lars (post 2010) for six unique bi­o­log­i­cal tar­gets. Fur­ther, more than 500 biosim­i­lars for 50+ unique bi­o­log­i­cal tar­gets are re­ported to be in var­i­ous stages of de­vel­op­ment.

Var­i­ous pub­licly avail­able mar­ket re­search re­ports in­di­cate that the biosim­i­lars mar­ket will be over $13 bil­lion by year 2024. It is pro­jected that bi­o­log­ics mar­ket will ex­ceed $390 bil­lion and ac­count for up to 28 per cent of the global phar­ma­ceu­ti­cals mar­ket by 2020. The biosim­i­lars mar­ket will con­tinue to grow as bi­o­logic patents con­tinue to ex­pire in the fu­ture.

The biosim­i­lars pipe­lines and ap­provals so far were pre­dom­i­nantly fo­cused on bi­o­log­i­cal tar­gets with patent ex­piries around 2020. Some re­fer to these tar­gets as “Wave I” biosim­i­lars. There are signs that com­pa­nies are now shift­ing their fo­cus to the next of bi­o­log­i­cal tar­gets with patent ex­piries in 2020-2025 and be­yond (termed “Wave II” tar­gets).

There are mul­ti­ple biosim­i­lars in de­vel­op­ment for any given bi­o­log­i­cal tar­get, with num­bers in dou­ble dig­its for some of the top sell­ing prod­ucts such as Hu­mira, Her­ceptin, Ri­tuxan /MabThera, Neu­lasta, Avastin. How­ever, the mar­ket may sup­port only a lim­ited num­ber of en­trants. Con­sol­i­da­tion of the multi­na­tional mar­kets is also ex­pected.

Pa­tient and pre­scriber ac­cep­tance of biosim­i­lars is also im­prov­ing with the emer­gence of more data.

This in­di­cates a strong fu­ture for biosim­i­lars though the ex­act dy­nam­ics on pric­ing and re­im­burse­ment are yet to emerge, es­pe­cially in the US mar­ket.

What role do you see of process in­no­va­tion and con­tract man­u­fac­tur­ing in its growth?

Biosim­i­lars de­vel­op­ment is a chal­leng­ing area as the pro­posed biosim­i­lars need to demon­strate a high de­gree of sim­i­lar­ity with the in­no­va­tor bi­o­logic in terms of their physic­o­chem­i­cal struc­ture, bi­o­log­i­cal

ac­tiv­ity, im­muno­genic­ity, phar­ma­coki­net­ics, phar­ma­co­dy­nam­ics, safety and ef­fi­cacy. The biosim­i­lars must be de­vel­oped within that de­fined de­sign space to match up to the char­ac­ter­is­tics of the ref­er­ence bi­o­log­ics.

Tech­no­log­i­cal ad­vances and in­no­va­tions have cer­tainly helped biosim­i­lars de­vel­op­ment in many ways such as in­crease in yield of pro­tein pro­duc­tion by em­ploy­ing an in­no­va­tive feed me­dia; re­duc­tion of over­all cost of man­u­fac­tur­ing process by im­prov­ing pu­rifi­ca­tion tech­niques and re­duc­ing pu­rifi­ca­tion steps. These a just a few ex­am­ples of process in­no­va­tion that took place since first bi­o­log­i­cal drugs be­came avail­able on the mar­kets in late 80s.

One im­por­tant area that is re­quired for biosim­i­lar drug de­vel­op­ment is map­ping out the in­no­va­tor bi­o­logic in terms of its struc­ture, physic­o­chem­i­cal prop­er­ties and bi­o­log­i­cal ac­tiv­ity through the demon­stra­tion of an­a­lyt­i­cal sim­i­lar­ity. The use of ad­vanced an­a­lyt­i­cal tech­niques for eval­u­a­tion po­tency and pu­rity of biosim­i­lars can con­trib­ute to stream­lin­ing the non-clin­i­cal and clin­i­cal de­vel­op­ment. Bi­o­log­ics with bet­ter im­pu­rity pro­files will likely have bet­ter safety (& im­muno­genic­ity) pro­files.

All these in­no­va­tions could po­ten­tially sup­port biosim­i­lars to be more com­pet­i­tive on the price terms and this would be very rel­e­vant as some ge­ogra­phies have ex­pe­ri­enced crowd­ing in this area with mul­ti­ple biosim­i­lars for a given in­no­va­tor bi­o­logic.

Do you think that reg­u­la­tion can have an im­pact on how the mar­ket evolves? If so, how?

Yes, reg­u­la­tions have def­i­nitely in­flu­enced the evo­lu­tion of biosim­i­lars mar­ket. For ex­am­ple, the EU reg­u­la­tors paved the way for biosim­i­lars around the globe. In the US, reg­u­la­tions have more slowly evolved and this led to re­luc­tance on the part of some biosim­i­lar spon­sors with global as­pi­ra­tions to en­ter this mar­ket.

Cur­rent reg­u­la­tions seem to pro­vide a fairly clear path­way for biosim­i­lars de­vel­op­ment and reg­is­tra­tion and the cur­rent biosim­i­lars reg­u­la­tions cre­ate a favourable en­vi­ron­ment for biosim­i­lar man­u­fac­tur­ers.

First and fore­most, reg­u­la­tory re­quire­ments for biosim­i­lars are in place in most of the largest mar­kets and the reg­u­la­tory ex­pec­ta­tions are be­com­ing more aligned. The reg­u­la­tions rightly rec­om­mend the devel­op­ers to fo­cus on es­tab­lish­ing ro­bust an­a­lyt­i­cal biosim­i­lar­ity as the ba­sis for ab­bre­vi­ated clin­i­cal and non-clin­i­cal de­vel­op­ment.

The fact that the guide­lines around the world are aligned is a very pos­i­tive in­flu­ence as this en­ables biosim­i­lar devel­op­ers to have global de­vel­op­ment pro­grammes that could sup­port mar­ket­ing au­tho­riza­tion in mul­ti­ple mar­kets at the same time. For ex­am­ple, when the ini­tial guide­lines were re­leased it was ex­pected that each reg­u­la­tory agency would like to see biosim­i­lar­ity stud­ies against the ref­er­ence bi­o­logic sourced from their own ju­ris­dic­tion.

How­ever, with the pas­sage of time, and pos­si­bly based on re­quests and feed­back from biosim­i­lar man­u­fac­tur­ers, the agen­cies are now ac­cept­ing that some of the piv­otal clin­i­cal data could be gen­er­ated in com­par­i­son with ref­er­ence bi­o­logic sourced from an­other ju­ris­dic­tion. How­ever, clear and strin­gent re­quire­ments ex­ist for pro­vi­sion of sci­en­tific bridg­ing data in sup­port of such an ap­proach.

Sim­i­larly, if the agen­cies in ma­jor mar­kets do not agree to have the same end­point for a piv­otal clin­i­cal study, it is still pos­si­ble to have a com­mon study pro­to­col with lo­cal amend­ments/adap­ta­tions.

Fur­ther many gov­ern­ments and gov­ern­ment agen­cies around the world have been con­sis­tently en­cour­ag­ing/rec­om­mend­ing/sup­port­ing the use of biosim­i­lars over in­no­va­tor bi­o­log­ics. Some of the no­table ex­am­ples in­clude the French healthy min­istry that is en­cour­ag­ing pre­scrip­tion of biosim­i­lars with the tar­get of start­ing at least 70 per cent of the new bi­o­log­i­cal pre­scrip­tions with the biosim­i­lars; Eng­land’s Na­tional Health Ser­vice (NHS) rec­om­men­da­tion that at least 90 per cent of new pa­tients should be pre­scribed the best value bi­o­log­i­cal medicine within 3 months of launch of a biosim­i­lar medicine and at least 80 per cent of ex­ist­ing pa­tients within 12 months; US FDA’s ed­u­ca­tional ini­tia­tives for health­care providers; and the Nor­we­gian Min­istry of Health and Care Ser­vices that funded the land­mark NorSwitch study to sup­port use/sub­sti­tu­tion of biosim­i­lar in­flix­imab.

More and more physi­cian ex­pert bod­ies such as the EULAR, ESMO, ASCO are en­dors­ing biosim­i­lars as vi­able treat­ment op­tions. Over­all, these are cre­at­ing a very con­ducive en­vi­ron­ment for the biosim­i­lars.

Dr Charu Manak­tala

MD, Head of Asia Pa­cific Biosim­i­lars Cen­ter of Ex­cel­lence at IQVIA

Newspapers in English

Newspapers from India

© PressReader. All rights reserved.