Pox­el, part­ner Sum­it­o­mo Dainip­pon taste suc­cess in first piv­otal test for oral di­a­betes drug

The French meta­bol­ic ex­perts at Pox­el and their Asian part­ners at Sum­it­o­mo Dainip­pon Phar­ma have hit a home run with the first late-stage Japan­ese test of their oral di­a­betes drug imeglim­in, which bodes well for the pair of Phase III tri­als ex­pect­ed to read­out lat­er this year and fu­els the block­buster ex­pec­ta­tions tagged on the mi­to­chon­dr­i­al ther­a­py.

The drug be­longs to a new chem­i­cal class of oral agents called ‘glim­ins’ that si­mul­ta­ne­ous­ly tar­get all three key or­gans in­volved in di­a­betes: the pan­creas, the liv­er and the mus­cles. Imeglim­in is de­signed to work on the two main de­fects seen in pa­tients with type II di­a­betes: by in­creas­ing in­sulin se­cre­tion in the pan­creas, in a glu­cose-de­pen­dent man­ner; and by de­creas­ing the ex­cess pro­duc­tion of glu­cose by the liv­er, while en­hanc­ing ‘in­sulin sen­si­tiv­i­ty’ in the mus­cles.

Thomas Kuhn, Pox­el

The TIMES 1 tri­al test­ed a 1000 mg dose of imeglim­in against a place­bo in 213 Japan­ese pa­tients with type 2 di­a­betes. The drug-in­duced a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion (p<0.0001) in HbA1c — av­er­age blood sug­ar lev­els over a pe­ri­od of weeks/months — at week 24, meet­ing the main goal. The place­bo-cor­rect­ed mean change in HbA1c from base­line was – 0.87%, the com­pa­nies said.

The drug al­so met the main sec­ondary goal of re­duc­ing fast­ing plas­ma glu­cose, and analy­ses of oth­er sec­ondary end­points are on­go­ing.

With an ag­ing pop­u­la­tion and grow­ing rates of obe­si­ty, di­a­betes in Japan has bal­looned, with the num­ber of sus­pect­ed di­a­bet­ics hit­ting a record 10 mil­lion for the first time in 2016, ac­cord­ing to gov­ern­ment es­ti­mates cit­ed by Nikkei.

“The TIMES 1 re­sults con­firm the ro­bust ef­fi­ca­cy com­bined with fa­vor­able safe­ty ob­served in the Phase 2b tri­al in Japan and the po­ten­tial ben­e­fits that Imeglim­in can bring to type 2 di­a­betes pa­tients glob­al­ly,” said Pox­el chief Thomas Kuhn. “The TIMES 1 da­ta is the first ma­jor step to­wards fil­ing the Japan­ese New Drug Ap­pli­ca­tion in 2020. Japan rep­re­sents the sec­ond largest sin­gle mar­ket for type 2 di­a­betes and, Asia, in broad­er terms, is con­sid­ered the most im­por­tant ge­o­graph­ic lo­ca­tion with re­gards to treat­ing the di­a­betes pan­dem­ic in the fu­ture.

In 2016, Pox­el re­port­ed that a Phase IIb tri­al in Japan reg­is­tered he­mo­glo­bin A1c re­duc­tions of 0.52%, 0.94% and 1.00% for the 500 mg, 1000 mg and 1500 mg dose twice-dai­ly. In 2017, the Mer­ck Serono spin­out forked over the Asia rights to the treat­ment to Sum­it­o­mo Dainip­pon Phar­ma in a deal worth up to $300 mil­lion.

Da­ta from TIMES-2 and TIMES-3 are ex­pect­ed lat­er this year. Pox­el (EPA: $POX­EL) out-li­censed the rights to imeglim­in in the Unit­ed States and Eu­rope to Vivek Ra­maswamy’s Roivant Sci­ences last year, with this part­ner fund­ing the ma­jor­i­ty of the cost­ly Phase III pro­gram ex­pect­ed to com­mence this year.

“Imeglim­in has a nov­el mech­a­nism of ac­tion as a mi­to­chon­dr­i­al bioen­er­get­ics en­hancer, po­ten­tial­ly pro­vid­ing a unique po­si­tion in the com­pet­i­tive type II di­a­betes treat­ment land­scape,” Jef­feries an­a­lysts wrote in a note last month. They mod­eled a 60% prob­a­bil­i­ty of com­mer­cial suc­cess for imeglim­in in the US/EU and Asia, with an es­ti­mate of $3.1 bil­lion in glob­al peak sales, in­clud­ing $600 mil­lion in Japan.


Im­age: Shut­ter­stock

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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