Gene ther­a­pies don’t have to cost $4 mil­lion: New pro­duc­tion plat­forms re­duce de­vel­op­ment costs and risks

Gene ther­a­py has emerged as a trans­for­ma­tive tech­nol­o­gy, of­fer­ing life-chang­ing treat­ments for con­di­tions with few op­tions. Sup­port­ed by re­cent FDA-ap­provals and a ro­bust in­dus­try-wide de­vel­op­ment pipeline, glob­al in­vest­ment in the gene ther­a­py field could surge from $18 bil­lion in 2023 to more than $97 bil­lion by 2033¹. But in large part due to man­u­fac­tur­ing lim­i­ta­tions, de­vel­op­ment stage gene ther­a­pies suf­fer from a dis­pro­por­tion­ate­ly high num­ber of reg­u­la­to­ry holds, and some mar­ket­ed ther­a­pies are priced at more than $4 mil­lion per dose². As more gene ther­a­pies progress to­ward com­mer­cial­iza­tion, man­u­fac­tur­ers face mount­ing pres­sure to im­prove scal­a­bil­i­ty, low­er pro­duc­tion costs and ac­cel­er­ate af­ford­able pa­tient ac­cess.

For the field to reach its full mar­ket and clin­i­cal po­ten­tial, de­vel­op­ers must over­come per­sis­tent ob­sta­cles in the pro­duc­tion and man­u­fac­tur­ing process­es that con­tribute to un­fa­vor­able de­vel­op­ment out­comes in­clud­ing reg­u­la­to­ry holds, fail­ures due to safe­ty, and scal­a­bil­i­ty chal­lenges, all of which dri­ve up de­vel­op­ment costs.

Lim­its of  tran­sient trans­fec­tion

Tran­sient trans­fec­tion dom­i­nates gene ther­a­py man­u­fac­tur­ing process­es, but this method—while ef­fec­tive in ear­ly-stage re­search—is chal­lenged to meet the de­mands of large-scale com­mer­cial pro­duc­tion. Re­quir­ing mul­ti­ple plas­mids and reagents, it is prone to batch fail­ures and presents re­pro­ducibil­i­ty chal­lenges.

The draw­backs of tran­sient trans­fec­tion be­come even more ev­i­dent at scale. Yield in­con­sis­ten­cies lim­it pro­duc­tion vol­ume and in­crease reg­u­la­to­ry hur­dles, in­creas­ing cost and time to reach pa­tients.

New tech­nolo­gies such as au­toma­tion and nov­el cell lines aim to im­prove con­sis­ten­cy and re­duce man­u­fac­tur­ing time­lines. But these ef­forts are lim­it­ed by their re­liance on tran­sient trans­fec­tion meth­ods. Al­ter­na­tive vec­tor pro­duc­tion plat­forms—such as those us­ing in­sect cells—show promise but have en­coun­tered chal­lenges re­lat­ed to reg­u­la­to­ry ap­proval and prod­uct con­sis­ten­cy.

In­no­va­tion in gene ther­a­py man­u­fac­tur­ing

De­vel­op­ers are ex­plor­ing al­ter­na­tive ap­proach­es to tran­sient trans­fec­tion gene ther­a­py pro­duc­tion and man­u­fac­tur­ing. Non-vi­ral gene ther­a­py vec­tors could help re­duce man­u­fac­tur­ing costs and ad­dress im­muno­genic­i­ty, how­ev­er, the tech­nol­o­gy is in very ear­ly stages. More­over, gene ther­a­pies pri­mar­i­ly re­ly on re­com­bi­nant ade­no-as­so­ci­at­ed virus (rAAV) vi­ral vec­tor de­liv­ery and these ap­proach­es will re­main the su­pe­ri­or ap­proach for many years to come.

To en­able large-scale man­u­fac­tur­ing of rAAVs and ush­er in the next decade of gene ther­a­py de­vel­op­ment, sta­ble, high-yield pro­duc­tion plat­forms are need­ed to re­place tran­sient trans­fec­tion meth­ods. Many com­pa­nies have at­tempt­ed to de­vel­op more cost-ef­fec­tive and high­er-yield rAAV pro­duc­tion sys­tems, but they’ve en­coun­tered sub­stan­tial hur­dles: deal­ing with rep/helper genes tox­ic to cells, achiev­ing op­ti­mal rAAV vi­ral titers and en­sur­ing sys­tem sta­bil­i­ty.

New­Bi­ologix is pi­o­neer­ing a sta­ble in­ducible rAAV pro­duc­er cell line plat­form ca­pa­ble of ad­dress­ing core lim­i­ta­tions of tran­sient trans­fec­tion sys­tems. By cre­at­ing sta­ble cell lines that pro­duce vi­ral vec­tors ef­fi­cient­ly and at scale, New­Bi­ologix’s plat­form is de­signed to elim­i­nate the need for re­peat­ed tran­sient plas­mid trans­fec­tions, sig­nif­i­cant­ly re­duc­ing pro­duc­tion time­lines and en­hanc­ing re­li­a­bil­i­ty dur­ing man­u­fac­tur­ing. With this plat­form, man­u­fac­tur­ers can ex­pect faster pro­duc­tion cy­cles, re­duced costs and im­proved batch con­sis­ten­cy—out­comes that are crit­i­cal for achiev­ing reg­u­la­to­ry ap­proval and scal­ing pa­tient ac­cess. For phar­ma­ceu­ti­cal com­pa­nies, pre­dictable man­u­fac­tur­ing process­es lead to high­er-qual­i­ty prod­uct, more ef­fi­cient tri­als and stream­lined com­mer­cial­iza­tion. For pa­tients, this can trans­late to faster, more af­ford­able ac­cess to life-chang­ing ther­a­pies.

In its com­mit­ment to de­vel­op­ing a sta­ble HEK293 cell line that con­sis­tent­ly pro­duces high-qual­i­ty, high-pu­ri­ty rAAVs, New­Bi­ologix is lay­ing the ground­work for a safe, re­li­able, and ro­bust rAAV pro­duc­tion sys­tem. The new­ly launched New­Bi­ologix Xcell™ Port­fo­lio fea­tures a com­pre­hen­sive suite of ad­vanced tech­nolo­gies aimed at achiev­ing ex­cel­lence in gene and cell ther­a­py pro­duc­tion. This in­cludes a high-per­for­mance en­gi­neered HEK293 cell line specif­i­cal­ly de­signed for rAAV pro­duc­tion, an ad­vanced plat­form that stream­lines the pro­duc­tion and test­ing of rAAV can­di­dates, and cus­tomized se­quenc­ing and bioin­for­mat­ics tools to an­a­lyze rAAV qual­i­ty. By in­te­grat­ing these com­po­nents, New­Bi­ologix is ac­cel­er­at­ing rAAV de­vel­op­ment at the pre­clin­i­cal stage, which will ul­ti­mate­ly re­duce the risk of fail­ure in drug de­vel­op­ment.

Look­ing ahead: Af­ford­able, ef­fec­tive and safe gene ther­a­py at scale

Es­ti­mates sug­gest that as many as 1 mil­lion peo­ple could ben­e­fit from gene ther­a­pies in the next 10 years³. In­no­va­tions in pro­duc­tion will en­sure the field can keep pace with its po­ten­tial and de­liv­er high vol­umes of gene ther­a­py prod­ucts at an af­ford­able cost.

New­Bi­ologix launched its Xcell Port­fo­lio Oc­to­ber 31. The plat­form in­cludes a suite of ad­vanced tech­nolo­gies de­signed for ex­cel­lence in gene & cell ther­a­py pro­duc­tion:

• Xcell™ Eng-HEK293 Cell Line: High-per­for­mance en­gi­neered HEK293 cell line for tran­sient rAAV pro­duc­tion.
• Xcell™ rAAV Pro­duc­tion & Test­ing Plat­form: Cut­ting-edge plat­form de­signed to stream­line the pro­duc­tion and test­ing of rAAV can­di­dates.
• Xcell™ Ge­nom­ic An­a­lyt­i­cal Plat­form: Tai­lored se­quenc­ing and bioin­for­mat­ics so­lu­tions to ad­dress a wide range of sci­en­tif­ic in­quiries.

“The Xcell Port­fo­lio draws on our lead­er­ship’s decades of ex­pe­ri­ence in cell line de­vel­op­ment and our fo­cus on pre­ci­sion, re­li­a­bil­i­ty, and scal­a­bil­i­ty,” said Ig­or Fisch, Ph.D., CEO of New­Bi­ologix. “We are com­mit­ted to cat­alyz­ing rAAV de­vel­op­ment for re­search in­sti­tu­tions, CD­MOs, and biotech­nol­o­gy and phar­ma­ceu­ti­cal com­pa­nies. Our in­no­v­a­tive suite of ser­vices and cell line so­lu­tions tack­les com­plex chal­lenges in gene ther­a­py pro­duc­tion, en­sur­ing that safe and ef­fec­tive treat­ments are ac­ces­si­ble to pa­tients.”

Learn more about New­Bi­ologix here.

Ref­er­ences:

¹Cell and Gene Ther­a­py Mar­ket Size Re­port, 2024-2033. (2024, April). Re­trieved from No­va One Ad­vi­sor web­site: https://www.no­vaonead­vi­sor.com/re­port/cell-and-gene-ther­a­py-mar­ket

²Drug Dis­cov­ery & De­vel­op­ment,With prices top­ping $4 mil­lion, high stakes de­fine cell and gene ther­a­py land­scape (2024, April). Re­trieved from Drug Dis­cov­ery & De­vel­op­ment web­site: https://www.drugdis­cov­ery­trends.com/how-price-safe­ty-and-ef­fi­ca­cy-shape-the-cell-and-gene-ther­a­py-land­scape/

³Na­tion­al Bu­reau of Eco­nom­ic Re­search, Es­ti­mat­ing the fi­nan­cial im­pact of gene ther­a­py in the U.S. (2021, April). Re­trieved from: https://nber.org/sys­tem/files/work­ing_pa­pers/w28628/w28628.pdf