BIOSIM­I­LARS GAIN­ING AC­CEPT­ABIL­ITY

BioSpectrum (Asia) - - Bio Content - Priyanka Ba­j­pai priyanka.ba­j­pai@mmac­tiv.com

The ex­pi­ra­tion of patents and other in­tel­lec­tual prop­erty rights of bi­o­log­i­cal in­no­va­tors over the next decade opens the op­por­tu­nity for biosim­i­lars to en­ter the mar­ket and in­crease com­pe­ti­tion among pro­duc­ers of bi­o­log­ics. A num­ber of new com­pa­nies are ex­pected to en­ter the biosim­i­lars mar­ket world­wide, in­clud­ing big pharma, small biotech, and generic par­tic­i­pants. Asia-pa­cific re­gion has the max­i­mum num­ber of biosim­i­lar prod­ucts in de­vel­op­ment cur­rently as com­pared to any­where else in the world, lead­ing to wealth of op­por­tu­ni­ties for in­ves­ti­ga­tors and pa­tients in­ter­ested in tak­ing part in biosim­i­lar clin­i­cal tri­als. In­dia, Ja­pan, South Korea, and China are par­tic­u­larly ac­tive in biosim­i­lar re­search ef­forts.

The ex­pi­ra­tion of patents and other in­tel­lec­tual prop­erty rights of bi­o­log­i­cal in­no­va­tors over the next decade opens the op­por­tu­nity for biosim­i­lars to en­ter the mar­ket and in­crease com­pe­ti­tion among pro­duc­ers of bi­o­log­ics. A num­ber of new com­pa­nies are ex­pected to en­ter the biosim­i­lars mar­ket world­wide, in­clud­ing big pharma, small biotech, and generic par­tic­i­pants. Asia-pa­cific re­gion has the max­i­mum num­ber of biosim­i­lar prod­ucts in de­vel­op­ment cur­rently as com­pared to any­where else in the world, lead­ing to wealth of op­por­tu­ni­ties for in­ves­ti­ga­tors and pa­tients in­ter­ested in tak­ing part in biosim­i­lar clin­i­cal tri­als. In­dia, Ja­pan, South Korea, and China are par­tic­u­larly ac­tive in biosim­i­lar re­search ef­forts.

The global biosim­i­lars drug mar­ket is ex­pected to grow from $2.6 bil­lion in 2014 to $26.5 bil­lion by 2020 (ac­cord­ing to Al­lied Mar­ket Re­search), thereby be­ing one of the fastest grow­ing seg­ments in global pharma. Ge­o­graph­i­cally, the global biosim­i­lars mar­ket is dom­i­nated by Europe, fol­lowed by Asi­a­Pa­cific, Rest of the World (RoW), and North Amer­ica. How­ever, the Asia-Pa­cific re­gion is likely to wit­ness the high­est growth rate dur­ing the fore­cast pe­riod. It is con­sid­ered that Asia-pa­cific re­gion has the max­i­mum num­ber of biosim­i­lar prod­ucts in de­vel­op­ment cur­rently as com­pared to any­where else in the world, lead­ing to wealth of op­por­tu­ni­ties for in­ves­ti­ga­tors and pa­tients in­ter­ested in tak­ing part in biosim­i­lar clin­i­cal tri­als. In­dia, Ja­pan, South Korea, and China are par­tic­u­larly ac­tive in biosim­i­lar re­search ef­forts.

Al­ter­na­tively re­ferred to as bio-phar­ma­ceu­ti­cals or fol­low-on bi­o­log­ics, biosim­i­lars dif­fer from gener­ics in the en­tire man­u­fac­tur­ing process, right from the raw ma­te­ri­als used in their man­u­fac­tur­ing.

Scott Fo­raker, GM and VP, Biosim­i­lars, Am­gen says, “Biosim­i­lar de­vel­op­ment is a highly skilled, mul­ti­step process re­quir­ing sig­nif­i­cant bi­o­log­ics ex­per­tise, in­fra­struc­ture and cap­i­tal in­vest­ment to suc­cess­fully bring these medicines to mar­ket. The fun­da­men­tal con­cept un­der­pin­ning the de­vel­op­ment path­way is that biosim­i­lars will not be, and are not re­quired to be, struc­turally iden­ti­cal to the ref­er­ence medicine, and it fol­lows that each biosim­i­lar will also dif­fer from an­other biosim­i­lar. Be­cause of this, we be­lieve that biosim­i­lars will look more like branded bi­o­log­ics than small mol­e­cule gener­ics across im­por­tant at­tributes like sci­en­tific dif­fi­culty, a cost of over $200 mil­lion to bring to mar­ket, man­u­fac­tur­ing com­plex­ity and a va­ri­ety of de­ci­sion-mak­ers, which are go­ing to re­quire pro­mo­tion de­tail and ed­u­ca­tion. Reg­u­la­tory path­ways which set ap­pro­pri­ately high stan­dards will be im­por­tant for en­sur­ing qual­ity, re­li­ably-sup­plied biosim­i­lar medicines are avail­able, and in es­tab­lish­ing both physi­cian and pa­tient con­fi­dence.”

A game changer for bio­pharma

With the ex­pected loss of patent ex­clu­siv­ity for some of the lead­ing bi­o­log­i­cal prod­ucts glob­ally over the next five to ten years (patents for more than 10 topselling bi­o­log­ics will ex­pire in the United States and Europe), there is a sig­nif­i­cant mar­ket op­por­tu­nity for the com­mer­cial­iza­tion of equally ef­fec­tive, lower cost biosim­i­lars.

The main driv­ers be­hind the emer­gence of this mar­ket are patent ex­piries on key bi­o­logic prod­ucts, bet­ter de­fined reg­u­la­tory path­ways, es­pe­cially in the Europe, and es­ca­lat­ing health­care costs which have prompted gov­ern­ments and in­sur­ers to find cost con­tain­ment so­lu­tions while main­tain­ing, or even im­prov­ing qual­ity of care.

Europe is the largest con­trib­u­tor of biosim­i­lar rev­enues world­wide. The mar­ket is ex­pected to have

“Most generic com­pa­nies have the tech­ni­cal know-how. They can lev­er­age their generic ex­pe­ri­ence for biosim­i­lars. Com­pa­nies that have suc­ceeded in Europe have strength­ened their R&D in­vest­ment and first-to-mar­ket strate­gies through col­lab­o­ra­tions. Re­luc­tance from physi­cians and pa­tients to pre­scribe and use biosim­i­lars be­cause of po­ten­tial ef­fi­cacy and safety is­sues might have a neg­a­tive im­pact in the mar­ket.” - Sanjeev Ku­mar, In­dus­try Man­agerAsia Pa­cific, Frost & Sul­li­van

an in­crease in de­mand for biosim­i­lar drugs with the in­crease in pres­sure from in­sur­ers and pay­ers for a re­duc­tion in med­i­cal ex­pen­di­ture. Sanjeev Ku­mar, In­dus­try Man­ager- Asia Pa­cific, Frost & Sul­li­van noted, “Most generic com­pa­nies have the tech­ni­cal know-how; there­fore, they can lev­er­age their generic ex­pe­ri­ence for biosim­i­lars. Com­pa­nies that have suc­ceeded in Europe have strength­ened their R&D in­vest­ment and first-to-mar­ket strate­gies through col­lab­o­ra­tions. Re­luc­tance from physi­cians and pa­tients to pre­scribe and use biosim­i­lars be­cause of po­ten­tial ef­fi­cacy and safety is­sues might have a neg­a­tive im­pact in the mar­ket.”

While the US is the largest bi­o­log­ics mar­ket glob­ally, it cur­rently ac­counts for only a small part of the global biosim­i­lars mar­ket. The emer­gence of a sup­port­ive reg­u­la­tory ap­proval path­way for biosim­i­lars and patent ex­piries on ma­jor bi­o­log­i­cal prod­ucts are ex­pected to make US one of the fastest grow­ing ma­jor mar­kets for biosim­i­lars in the next five to ten years. In the mean­time, the EU and other ma­jor mar­kets in rest of the world are also ex­pected to see mul­ti­ple biosim­i­lars launches and sig­nif­i­cant growth in the mar­ket size.

Al­though the prod­ucts have been avail­able else­where—in­clud­ing Europe—for sev­eral years, physi­cians and other key stake­hold­ers in the United States have only re­cently be­gun to an­tic­i­pate their ar­rival. Com­ment­ing on the present sit­u­a­tion of the mar­ket, Sanjeev Ku­mar said, “While cur­rent reg­u­la­tions al­low for the ap­proval of generic copies of con­ven­tional phar­ma­ceu­ti­cals at greatly re­duced costs, un­til re­cently there has not been the tech­nol­ogy nor the reg­u­la­tory path­way with which to in­tro­duce lower-cost ver­sions of bi­o­log­ics. The U.S. Con­gress re­cently en­acted leg­is­la­tion to en­able and en­cour­age the in­tro­duc­tion of biosim­i­lars/fol­low-on bi­o­log­ics, paving the way into an un­tapped mar­ket. How­ever, many ob­sta­cles to a clear ab­bre­vi­ated reg­u­la­tory path­way and mar­ket up­take in the US re­main, such as guid­ance re­gard­ing clin­i­cal re­search re­quire­ments, nam­ing con­ven­tion, and en­duser ac­cep­tance to name a few.”

In ad­di­tion to the above fac­tors, across all mar­kets, the in­tro­duc­tion of more af­ford­able and equally ef­fec­tive biosim­i­lars is ex­pected to in­crease us­age of bi­o­log­i­cal prod­ucts among pa­tients who cur­rently can­not af­ford such a treat­ment op­tion.

Driv­ing the mar­ket

The ex­pi­ra­tion of patents and other in­tel­lec­tual prop­erty rights of bi­o­log­i­cal in­no­va­tors over the next decade opens the op­por­tu­nity for biosim­i­lars to en­ter the mar­ket and in­crease com­pe­ti­tion among pro­duc­ers of bi­o­log­ics. The rea­son for this op­por­tu­nity is to en­sure that pa­tients get ac­cess to the ben­e­fits of suc­cess­ful block­buster drugs at a re­duced price. Over a pe­riod of time, the num­ber of patent ex­piries will in­flu­ence the mar­ket.

The high cost of bi­o­log­ics will spur pay­ers to look to biosim­i­lars for cost sav­ings. The price of biosim­i­lars is 20 per cent to 30 per cent lower than the in­no­va­tor bi­o­logic prod­ucts. Spe­cialty bi­o­log­ics are among the most ex­pen­sive medicines, rang­ing in price from $5,000 to $300,000 per year. Over the next 4 to 5 years, the mar­ket will see an up­take of more biosim­i­lar drugs.

A num­ber of new com­pa­nies are ex­pected to en­ter the biosim­i­lars mar­ket world­wide, in­clud­ing big pharma, small biotech, and generic par­tic­i­pants. In par­tic­u­lar, some In­dian par­tic­i­pants such as Dr Reddy’s, Shan­tha Biotech, and Reliance Life Sciences

are aim­ing to en­ter the Euro­pean mar­ket. Sanjeev Ku­mar is very hope­ful of a bright biosim­i­lars fu­ture. “Be­cause of lim­ited ex­pe­ri­ence, ini­tially these com­pa­nies may take some time to cap­i­tal­ize on the Euro­pean biosim­i­lars mar­ket. How­ever, in the next 5 to 7 years, the con­tri­bu­tions of the above com­pa­nies in terms of new prod­ucts and rev­enue will boost the mar­ket. The in­creas­ing num­ber of biosim­i­lar ap­provals in Ja­pan, In­dia, LATAM, and other re­gions and the fi­nan­cial strength of the big pharma and generic com­pa­nies are some of the rea­sons for the emer­gence of new mar­ket par­tic­i­pants”, he says.

Ramp­ing up ca­pa­bil­i­ties in Asia

Sin­ga­pore is a highly ef­fi­cient and a busi­ness-friendly place and pro­motes com­pa­nies with highly qual­i­fied labour and sup­port from pub­lic in­sti­tu­tions. This makes it an easy ac­cess to trans­porta­tion routes serv­ing Asia and the world. Swiss health­care gi­ant No­var­tis, opened a $500 mil­lion man­u­fac­tur­ing plant in Sin­ga­pore in 2017 that can pro­duce both bi­o­log­ics and biosim­i­lars. It also sited the Asia Pa­cific head­quar­ters of its San­doz di­vi­sion, which con­cen­trates on biosim­i­lars and generic phar­ma­ceu­ti­cals, in Sin­ga­pore.

In 2014, Am­gen, based in Amer­ica and one of the world’s lead­ing biotech­nol­ogy com­pa­nies, also opened a S$200 mil­lion bi­o­log­ics man­u­fac­tur­ing plant in Sin­ga­pore, its first in Asia. The firm cur­rently has many biosim­i­lars in its pipe­line, in ad­di­tion to a biosim­i­lar for in­flam­ma­tory dis­eases (AMJEVITA) that has been ap­proved by the United States Food and Drug Ad­min­is­tra­tion (US FDA). While the Sin­ga­pore plant cur­rently does not pro­duce biosim­i­lars, Am­gen is well­po­si­tioned to sup­port the com­pany’s global growth.

Talk­ing about Am­gen’s ap­proach to biosim­i­lars mar­ket, Scott Fo­raker noted, “As a lead­ing bi­o­log­ics in­no­va­tor and biosim­i­lar de­vel­oper, Am­gen has de­signed our biosim­i­lars ap­proach and prod­uct de­vel­op­ment pro­grams to di­rectly ad­dress the need for con­fi­dence in bi­o­logic qual­ity, and to con­tinue to com­mit a reli­able sup­ply. With nearly four decades of bi­o­log­ics ex­pe­ri­ence, our biosim­i­lars are sub­ject to the same rigor, stan­dard op­er­at­ing pro­ce­dures and qual­ity con­trols as our in­no­va­tor medicines. To en­sure reli­able sup­ply, we also man­u­fac­ture our biosim­i­lars along­side Am­gen’s in­no­va­tive bi­o­log­ics in our cut­ting-edge fa­cil­i­ties. Am­gen is spe­cial­ized in un­lock­ing the po­ten­tial of bi­ol­ogy to cre­ate new ways to com­bat the most dif­fi­cult dis­eases. With the growth

“Biosim­i­lar de­vel­op­ment is a highly skilled, multi-step process re­quir­ing sig­nif­i­cant bi­o­log­ics ex­per­tise, in­fra­struc­ture and cap­i­tal in­vest­ment to suc­cess­fully bring these medicines to mar­ket. The fun­da­men­tal con­cept un­der­pin­ning the de­vel­op­ment path­way is that biosim­i­lars will not be, and are not re­quired to be, struc­turally iden­ti­cal to the ref­er­ence medicine, and it fol­lows that each biosim­i­lar will also dif­fer from an­other biosim­i­lar. Be­cause of this, we be­lieve that biosim­i­lars will look more like branded bi­o­log­ics than small mol­e­cule gener­ics across im­por­tant at­tributes like sci­en­tific dif­fi­culty, a cost of over $200 mil­lion to bring to mar­ket, man­u­fac­tur­ing com­plex­ity and a va­ri­ety of de­ci­sion-mak­ers, which are go­ing to re­quire pro­mo­tion de­tail and ed­u­ca­tion. Reg­u­la­tory path­ways which set ap­pro­pri­ately high stan­dards will be im­por­tant for en­sur­ing qual­ity, re­li­ably-sup­plied biosim­i­lar medicines are avail­able, and in es­tab­lish­ing both physi­cian and pa­tient con­fi­dence.” - Scott Fo­raker, GM and VP, Biosim­i­lars, Am­gen

of Am­gen’s port­fo­lio of 10 biosim­i­lars, we are ex­cited for the fu­ture and our strength­ened abil­ity to reach ad­di­tional pa­tients around the world.

To bol­ster their po­si­tion in Asia’s biosim­i­lars mar­ket, Am­gen and other Western com­pa­nies are also ink­ing col­lab­o­ra­tions with Asian firms. In Septem­ber 2017, for in­stance, Am­gen an­nounced an agree­ment with Chi­nese phar­ma­ceu­ti­cal com­pany Sim­cere to co-de­velop, man­u­fac­ture and man­age the ap­proval ap­pli­ca­tion process for four of its biosim­i­lars for the Chi­nese mar­ket.

Lead­ing Asian com­pa­nies them­selves are ramp­ing up their ef­forts in biosim­i­lars re­search and de­vel­op­ment. In 2012, the South Korean elec­tron­ics and health­care gi­ant Sam­sung Group joined forces with Amer­i­can biotech­nol­ogy com­pany Bio­gen to form a joint ven­ture fo­cused on bio­phar­ma­ceu­ti­cals, called Sam­sung Bioepis. To ac­cel­er­ate its de­vel­op­ment of a biosim­i­lar ver­sion of En­brel, a prom­i­nent rheuma­toid arthri­tis drug cre­ated by Am­gen, Bioepis set aside 100 biore­ac­tors and as­signed 300 re­searchers to over­see 1,500 ex­per­i­ments. In 2016, and af­ter just four

years of de­vel­op­ment, it was the first to in­tro­duce its etan­er­cept biosim­i­lar in Europe where Wyeth mar­kets En­brel. Most biosim­i­lars take eight to 10 years. Very re­cently in Jan­uary 2018, Bio­gen an­nounces to up its share in Sam­sung Bioepis ow­ing to the record biosim­i­lar rev­enues. This has been made pos­si­ble due to the re­cent ap­provals and launches of biosim­i­lar prod­ucts by Bioepis.

Is­sues need at­ten­tion

Al­though it is gen­er­ally ex­pected that biosim­i­lars will emerge as a rapidly grow­ing seg­ment of the bio­phar­ma­ceu­ti­cal in­dus­try, their up­take faces sev­eral chal­lenges.

The reg­u­la­tory poli­cies gov­ern­ing biosim­i­lars are still in flux, with ma­jor mar­kets like China lack­ing con­sis­tent and clear path­ways. The United States is­sued draft biosim­i­lars guid­ance in 2013, and al­though the FDA re­cently ap­proved the fil­gras­tim biosim­i­lar, the agency fi­nal­ized a for­mal ap­proval path­way only till late 2016.

Un­cer­tain­ties and risks for biosim­i­lar man­u­fac­tur­ers will con­tinue to be rel­a­tively high ini­tially. The lack of clear guide­lines on sub­sti­tutabil­ity and in­ter­change­abil­ity with ref­er­ence bi­o­log­ics will likely cause physi­cians to ex­er­cise more cau­tion in pre­scrib­ing biosim­i­lars un­til they gain com­fort with the qual­ity and ef­fi­cacy of biosim­i­lars. Sanjeev Ku­mar noted, “This re­sis­tance may af­fect the mar­ket heav­ily and bring down the prob­a­bil­ity of suc­cess for early use of biosim­i­lars. Over a pe­riod of time, this sce­nario will likely change as more ex­pe­ri­ence and ed­u­ca­tion in biosim­i­lars may pro­duce greater ac­cept­abil­ity.

The dis­ad­van­tage of biosim­i­lar man­u­fac­tur­ers is that they do not have ac­cess to the long-term safety and ef­fi­cacy data or the pro­duc­tion process in­for­ma­tion of the orig­i­na­tor prod­ucts. The biosim­i­lar man­u­fac­tur­ing process is com­plex and deals with a cell-based process, and each drug is prod­uct spe­cific. This may lead to man­u­fac­tur­ing dif­fi­cul­ties in terms of con­sis­tency and qual­ity is­sues.”

The time­line for ap­proval of biosim­i­lars from the clin­i­cal stage to the com­mer­cial prod­uct is ap­prox­i­mately 6 to 10 years, which is longer when com­pared to gener­ics (3 to 4 years). In con­text to this, Sanjeev Ku­mar adds, “The com­plex­ity of the man­u­fac­tur­ing process, nu­mer­ous clin­i­cal tests in­volved, and safety and ef­fi­cacy con­cerns have led to a pro­longed ap­proval time. The longer wait­ing time may hin­der mar­ket growth, thereby cre­at­ing a de­mand and sup­ply gap af­ter patent ex­piry of block­buster bi­o­log­ics.”

Even af­ter ap­proval, prof­itabil­ity of biosim­i­lars could be hurt by in­no­va­tors re­duc­ing prices to make biosim­i­lars cost pro­hib­i­tive.

Fu­ture ahead

As a re­sult of ma­jor patent ex­pi­ra­tions for block­buster bi­o­log­ics, the global biosim­i­lars mar­ket is ex­pected to grow, es­pe­cially with the new leg­is­la­tion for biosim­i­lars in the United States, Ja­pan, and other APAC coun­tries. Physi­cians may be more or less will­ing to pre­scribe biosim­i­lars, de­pend­ing on the in­di­ca­tion (can­cer or im­muno­log­i­cal dis­or­ders). Biosim­i­lars for chronic dis­eases will ex­pe­ri­ence con­tin­u­ous de­mand with lower costs. Also, prod­ucts with dif­fer­ent ad­min­is­tra­tion routes may gain favour over less de­sir­able meth­ods.

Launch of in­no­va­tive pro­duc­tion plat­forms will re­duce the cost of biosim­i­lar pro­duc­tion and thereby pro­vide sub­stan­tial price dif­fer­en­ti­a­tion. Though the tra­di­tional ex­pres­sion sys­tems are ex­pen­sive and re­quire a lengthy time­line for process op­ti­miza­tion and achiev­ing the de­sired yield, they are still be­ing used for pro­duc­tion of bi­o­log­ics at gram to kilo­gram quan­ti­ties. Hence, biosim­i­lar firms are look­ing at novel plat­forms, which would help them to shorten the time by rapidly as­sess­ing drug can­di­dates and pro­duc­ing prod­ucts for pre­clin­i­cal and clin­i­cal stud­ies in a short­ened time­frame. The new sys­tems will likely meet the needs of biosim­i­lar devel­op­ers in the com­ing years.

Newspapers in English

Newspapers from India

© PressReader. All rights reserved.