The big plas­ma al­liance spear­head­ed by Take­da and CSL Behring has a big Phase III ver­dict: Adding their hy­per­im­mune in­tra­venous im­munoglob­u­lin prod­uct to Gilead’s remde­sivir does not stall dis­ease pro­gres­sion.

Dubbed H-Ig, the treat­ment was sup­posed to be a high­er grade ver­sion of con­va­les­cent plas­ma, which for­mer Pres­i­dent Don­ald Trump once hailed as a “his­toric break­through.” But it seems to be fol­low­ing plas­ma down the same path to­ward ob­so­les­cence.

Julie Kim

Com­ing a year af­ter the com­pa­nies an­nounced the part­ner­ship — which they called a bold move to find an­swers amid un­cer­tain­ty — the fail­ure would mark an end to their work, which had in­clud­ed man­u­fac­tur­ing the prod­uct at-risk.

“We are es­pe­cial­ly proud that we pooled re­sources, brought our plas­ma ex­per­tise and in­fra­struc­ture to­geth­er at our own cost to ben­e­fit pub­lic health and added to our un­der­stand­ing of a com­plex field,” said Julie Kim, pres­i­dent of Take­da’s plas­ma-de­rived ther­a­pies busi­ness unit. She co-led the ini­tia­tive with Bill Mez­zan­otte, head of R&D at CSL Behring.

Fund­ed by the NIH, the ITAC tri­al had en­rolled 600 adult pa­tients hos­pi­tal­ized for Covid-19 across 11 coun­tries and of­fered them in­ves­ti­ga­tion­al H-Ig plas­ma treat­ments. In ad­di­tion to Take­da and CSL Behring, Emer­gent BioSo­lu­tions and Gri­fols al­so sup­plied some of the clin­i­cal ma­te­r­i­al, which was processed and pu­ri­fied in a way that re­sult­ed in more con­cen­trat­ed neu­tral­iz­ing an­ti­body ac­tiv­i­ty while min­i­miz­ing safe­ty is­sues.

“IgG con­cen­tra­tion and IgG spe­cif­ic to SARS-CoV-2 were in­creased over 10-fold from con­va­les­cent plas­ma to the fi­nal prod­uct,” a group from Gri­fols de­scribed in a re­cent pa­per. “Nor­mal­ized en­zyme-linked im­munosor­bent as­say ac­tiv­i­ty (per mg/ml IgG) was main­tained through­out the process. Pro­tein con­tent in these fi­nal prod­uct batch­es was 100% IgG, con­sist­ing of 98% monomer and dimer forms. Po­ten­tial­ly haz­ardous pro­teins (IgM, IgA, and an­ti-A, an­ti-B, and an­ti-D) were re­duced to min­i­mal lev­els.”

In­ves­ti­ga­tors com­pared the clin­i­cal sta­tus of pa­tients in each group on day 7 of fol­lowup, mea­sur­ing a spec­trum of out­comes from lim­it­ing symp­toms to death. The com­pa­nies didn’t say much be­yond the fact that H-Ig didn’t meet the pri­ma­ry end­point, say­ing they will pub­lish the re­sults lat­er.

The hos­pi­tal­ized pa­tient pop­u­la­tion has been an elu­sive group for an­ti­bod­ies, de­feat­ing a slew of can­di­dates from Eli Lil­ly, Glax­o­SmithK­line/Vir and Brii Bio.

Plas­ma from healthy donors who have re­cov­ered from Covid-19, mean­while, has al­so had trou­ble liv­ing up to ear­ly ex­pec­ta­tions.

The UK’s RE­COV­ERY tri­al stopped re­cruit­ing pa­tients for its con­va­les­cent plas­ma arm af­ter an in­de­pen­dent da­ta mon­i­tor­ing com­mit­tee found no sig­nif­i­cant im­prove­ment in mor­tal­i­ty.

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