With two can­cer drugs on the mar­ket, the spot­light is on Agios’ rare meta­bol­ic dis­ease fran­chise led by mi­tapi­vat, its ex­per­i­men­tal drug un­der de­vel­op­ment for a range of con­di­tions in­clud­ing pyru­vate ki­nase de­fi­cien­cy, tha­lassemia, and sick­le cell dis­ease.

At the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion An­nu­al Con­gress (EHA), the com­pa­ny is­sued two up­dates on the ef­fect of mi­tapi­vat — a drug de­signed to tar­get pyru­vate ki­nase-R (PKR), an en­zyme in­volved in the con­ver­sion of sug­ar, or glu­cose, in­to en­er­gy that is crit­i­cal for the sur­vival of red blood cells.

The first up­date came from an on­go­ing mid-stage study test­ing the drug in two forms of tha­lassemia, an in­her­it­ed blood dis­or­der. In the study, 12 out of 13 pa­tients saw sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments in he­mo­glo­bin con­cen­tra­tion, set­ting the stage for a piv­otal tri­al next year.

The tri­al, which has so far en­rolled 20 pa­tients, is eval­u­at­ing the ef­fect of the drug in more mod­er­ate forms of the dis­ease, in pa­tients that are not de­pen­dent on blood trans­fu­sions. Pa­tients start­ed on a low­er 50 gm dose and then were grad­u­al­ly giv­en the high­er 100 mg dose.

Tha­lassemia, caused by mu­ta­tions al­pha or be­ta glo­bin genes, is char­ac­ter­ized by ei­ther no or too lit­tle he­mo­glo­bin — the pro­tein that trans­ports oxy­gen in red blood cells. Pa­tients can ex­pe­ri­ence a range of symp­toms such as ane­mia, weak­ness, frag­ile bones and di­min­ished fer­til­i­ty.

The main goal of  ≥ 1.0 g/dL in­crease in Hb con­cen­tra­tion was met by about 92% of the 13 pa­tients ready for eval­u­a­tion fol­low­ing 12 weeks of treat­ment — the mean change from base­line for the evalu­able pa­tients was 1.34 g/dL over weeks 4-12. Oth­er mark­ers of red blood cell func­tion and per­for­mance al­so fa­vored the drug.

Ac­celeron’s Re­blozyl, which is en­gi­neered to work by tar­get­ing a pro­tein nec­es­sary to en­hance the pro­duc­tion and mat­u­ra­tion of red blood cells, was ap­proved last year for more se­vere be­ta-tha­lassemia pa­tients who are trans­fu­sion-de­pen­dent. Mean­while, blue­bird bio, has an eye-pop­ping­ly ex­pen­sive gene ther­a­py to com­bat the dis­ease ap­proved in Eu­rope, and is aim­ing for a US nod.

Jack­ie Fouse

Akin to blue­bird, whose gene ther­a­py is al­so primed for use in sick­le cell dis­ease, Jack­ie Fouse-led Agios is al­so test­ing mi­tapi­vat in the blood dis­or­der that is char­ac­ter­ized by atyp­i­cal he­mo­glo­bin mol­e­cules, which can dis­tort red blood cells in­to a sick­le, or cres­cent, shape.

Ear­ly da­ta from an on­go­ing phase I SCD tri­al test­ing mul­ti­ple mi­tapi­vat dos­es (5 mg, 20 mg, 50 mg) showed the com­pa­ny had en­rolled 9 pa­tients till date — each got the drug for two weeks, be­fore be­ing ta­pered off. One pa­tient dis­con­tin­ued the tri­al due to a pre-ex­ist­ing con­di­tion, but the re­main­ing 8 were eval­u­at­ed.

Five out of 8 pa­tients achieved the main goal of en­hanc­ing he­mo­glo­bin lev­els by  ≥1.0 g/dL from base­line. Da­ta showed the use of the drug was as­so­ci­at­ed with de­creas­es in he­molyt­ic mark­ers.

Un­til re­cent­ly, the treat­ment land­scape for the dis­ease was bar­ren, but the last few years have seen a tri­fec­ta of ap­provals. Most re­cent­ly, last No­vem­ber saw two ap­provals: No­var­tis’ ther­a­py, Adakveo, de­signed to pre­vent pe­ri­od­ic episodes of sear­ing pain called va­so-oc­clu­sive crises (VOCs) that de­prive the body of oxy­gen-rich blood and Glob­al Blood Ther­a­peu­tics’ Oxbry­ta, which works by in­creas­ing he­mo­glo­bin’s affin­i­ty for oxy­gen. Mi­tapi­vat is ex­pect­ed to work in SCD by de­creas­ing a salt in red blood cells that plays a role in lib­er­at­ing oxy­gen from he­mo­glo­bin in pe­riph­er­al cir­cu­la­tion and en­hanc­ing lev­els of a cen­tral metabo­lite called adeno­sine triphos­phate (ATP).

Agios al­so has two piv­otal stud­ies test­ing mi­tapi­vat in pyru­vate ki­nase de­fi­cien­cy, a rare in­her­it­ed dis­ease that is char­ac­ter­ized by the ac­cel­er­at­ed de­struc­tion of red blood cells. Da­ta from these tri­als are ex­pect­ed lat­er this year or ear­ly 2021.

Sep­a­rate­ly on Fri­day, Agios said it was re­lin­quish­ing its roy­al­ty rights on glob­al net sales of Bris­tol My­ers Squibb’s Id­hi­fa, as as its rights to re­ceive up to $55 mil­lion in out­stand­ing reg­u­la­to­ry mile­stone pay­ments from Bris­tol My­ers Squibb, to Roy­al­ty Phar­ma for $255 mil­lion.

The drug, al­lied with Cel­gene (now a Bris­tol My­ers com­pa­ny), was ap­proved in 2017 for use in acute myeloid leukemia.

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Sanofi chief executive Paul Hudson told investors earlier this year that the Big Pharma was going to emphasize its sales kingpin Dupixent moving forward.

He wasn’t joking — the megablockbuster drug and sales king, recording just shy of $2 billion in sales this past quarter, has now officially secured its fifth indication from the FDA.

Sanofi and Regeneron, who jointly work on Dupixent development and commercialization, announced the new development on Thursday, saying that the FDA gave the all-clear to Dupixent to treat patients with prurigo nodularis, a rare autoimmune disorder characterized by a persistent, severe itch — and also visualized by hard, extremely itchy bumps known as nodules that form on the skin. The FDA noted in its announcement that it is the agency’s first approval for the disease.

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.