Can­cer drug­mak­er Agios of­fers promis­ing da­ta from two stud­ies test­ing blood dis­or­der drug

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.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

BREAK­ING: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

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.

Marcelo Bigal, Ventus Therapeutics CEO

No­vo Nordisk joins No­var­tis, Roche in NL­RP3 are­na, bet­ting $70M cash on NASH, car­diometa­bol­ic us­es

As a drug target, the NLRP3 inflammasome has drawn serious interest from Big Pharma, inspiring a series of M&A deals from Novartis and Roche on top of venture investments by others. Now Novo Nordisk is jumping on the bandwagon — and the Danish pharma giant is taking the target where it knows best.

Novo Nordisk is getting its NLRP3 inhibitors from Ventus Therapeutics, a Versant-backed startup that set out to make some of the best NLRP3 drugs out there by incorporating new insights into the structure of the target complex.

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Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

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.

Paul Hudson, Sanofi CEO (Photographer: Cyril Marcilhacy/Bloomberg via Getty Images)

Sanofi, Re­gen­eron’s Dupix­ent scores an­oth­er in­di­ca­tion with first-ever ap­proval for nodu­lar skin dis­or­der

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 names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

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.