Manufacturing advances are improving gene therapy treatments

Med­ical sci­ence is rac­ing ahead as it decodes com­plex genet­ics to reveal routes to ther­a­pies and cures to the most intractable dis­eases blight­ing soci­ety.

Cell and gene ther­a­pies are boom­ing, with CAR‑T cell treat­ments recog­nis­ing and neu­tral­is­ing even the most shroud­ed can­cers and Crispr gene edit­ing tech­niques reach­ing land­mark approvals to tack­le rare, life-threat­en­ing con­di­tions.

But the sci­ence – along with its life­lines to patients – stalls if the mechan­ics of test­ing and man­u­fac­tur­ing the prod­ucts at scale do not keep pace.

The sci­en­tists who dis­cov­ered Crispr and its rev­o­lu­tion­ary abil­i­ty to change the DNA of ani­mals, plants and microor­gan­isms were award­ed the Nobel Prize in Chem­istry and their work is lead­ing to huge steps towards cur­ing inher­it­ed dis­eases. How­ev­er, the costs of enabling this dis­cov­ery, and oth­er gene and cell ther­a­pies, is as daunt­ing as the mol­e­c­u­lar com­plex­i­ty but con­tract test­ing devel­op­ment and man­u­fac­tur­ing organ­i­sa­tion WuXi Advanced Ther­a­pies – the advanced ther­a­pies busi­ness unit of WuXi AppTec based in the heart of the cell and gene ther­a­py indus­try – has refined man­u­fac­tur­ing plat­forms that accel­er­ate these ther­a­pies to mar­ket.

The company’s inno­va­tion arm, Oxford-based Oxgene, spe­cialis­es in dis­cov­ery and bio­man­u­fac­tur­ing tech­nolo­gies that feed into an end-to-end ser­vice that ensures trans­for­ma­tive sci­ence reach­es the mar­ket and, ulti­mate­ly, the patient.

“We are pas­sion­ate about improv­ing and accel­er­at­ing patient access to the cell and gene ther­a­pies that could change, or even save, their lives, which we do through long-last­ing and mean­ing­ful part­ner­ships with our cus­tomers,” says David Chang, chief exec­u­tive offi­cer at WuXi Advanced Ther­a­pies.

He adds: “Man­u­fac­tur­ing these prod­ucts with con­sis­ten­cy involves major chal­lenges. It is one thing to have the bright idea, but it takes extra rounds of effort, exper­tise and inge­nu­ity to make it com­mer­cial­ly viable – and that is what we live and breathe.”

Research has iden­ti­fied the man­u­fac­tur­ing chal­lenge cell and gene ther­a­py faces in clin­i­cal test­ing and com­mer­cial­i­sa­tion with the impli­ca­tions rever­ber­at­ing from R&D through clin­i­cal tri­als to reim­burse­ment. The man­u­fac­tur­ing process involves liv­ing cells with inher­ent vari­abil­i­ty and high risk from con­t­a­m­i­nants.

Chang says: “We analyse the process, see the bot­tle­necks and inno­vate around them. It is a dif­fi­cult and eco­nom­i­cal­ly tox­ic process. Typ­i­cal­ly, a research insti­tute or a spin­off com­pa­ny will have a great idea but no expe­ri­ence of how to take it to com­mer­cial­i­sa­tion. WuXi Advanced Ther­a­pies has an end-to-end ser­vice which acts as a turnkey solu­tion to help them realise their ambi­tions.”

The annu­al Mass Gen­er­al Brigham ‘Dis­rup­tive Dozen’ report, which show­cas­es emerg­ing gene and cell ther­a­py (GCT) tech­nolo­gies, this year iden­ti­fied break­throughs such as restor­ing sight by mend­ing bro­ken genes, CAR‑T ther­a­pies that take aim at autoim­mune con­di­tions, engi­neer­ing can­cer-killing cells that assault sol­id tumours and har­ness­ing RNA to treat brain can­cer. Even more recent­ly, the Euro­pean Med­i­cines Author­i­ty (EMA) has approved the first gene ther­a­py to be deliv­ered direct­ly into the brain for treat­ment of adults and chil­dren with severe aro­mat­ic L‑amino acid decar­boxy­lase (AADC) defi­cien­cy who have a genet­i­cal­ly con­firmed diag­no­sis, and the New Eng­land Jour­nal of Med­i­cine report­ed pos­i­tive results from a phase I‑2 gene ther­a­py tri­al in patients with hemo­phil­ia B.

The US-based aca­d­e­m­ic health­care sys­tem is part of a glob­al push to advance cell and gene ther­a­py to trans­form can­cer care and treat con­di­tions that cur­rent­ly have min­i­mal ther­a­pies and no cures.

“These are excit­ing times and we now have treat­ments for patients who pre­vi­ous­ly had no option. Every cell and gene ther­a­py that makes it to the clin­ic or com­mer­cial­i­sa­tion is a huge step for­ward,” says Dr Ryan Cawood, Oxgene founder and chief sci­en­tif­ic offi­cer at WuXi Advanced Ther­a­pies. “Ten years ago, there wasn’t the fund­ing, the infra­struc­ture or man­u­fac­tur­ing capa­bil­i­ty. Now, we have the plat­forms to see if these prod­ucts are viable at a much faster pace. We then have the tech­nol­o­gy and exper­tise to make them hap­pen and take them to com­mer­cial­i­sa­tion.”

Oxgene has devel­oped the Tes­sa sys­tem that allows for large scale ade­no-asso­ci­at­ed virus (AAV) pro­duc­tion that helps reduce the cost of cell and gene ther­a­py man­u­fac­ture with­out com­pro­mis­ing on safe­ty. It is part of a suite of tech­nolo­gies that are ener­gis­ing the sec­tor and, cru­cial­ly, attract­ing investors to sup­port ear­ly-stage sci­ence because they reduce the once pro­hib­i­tive costs of tak­ing some prod­ucts to com­mer­cial­i­sa­tion.

“We are work­ing with cells, which are dif­fi­cult to char­ac­terise and very dif­fi­cult to work with, in com­par­i­son to small mol­e­cules,” adds Cawood. “But, because they have all of those com­plex­i­ties, they have a huge amount of advan­tages; they can adapt, they can respond, they can inter­act with human biol­o­gy in ways that small mol­e­cules sim­ply can’t.”

WuXi Advanced Ther­a­pies is com­mit­ted to being an influ­en­tial part­ner on the jour­ney from idea to trans­for­ma­tive treat­ment. Chang adds: “Our plat­forms offer the abil­i­ty to fine tune test­ing and man­u­fac­ture in the short­est pos­si­ble time and we pride our­selves on the oppor­tu­ni­ties our sys­tems pro­vide for indus­try. These tech­niques offer so much poten­tial to sci­en­tists, new and exist­ing com­pa­nies and, most impor­tant­ly, to patients. It means hope.”

To find out more, please vis­it advancedtherapies.com

Pro­mot­ed by Oxgene