Lit­tle Alder bags pos­i­tive PhI­II mi­graine da­ta, but gi­ant ri­vals are rac­ing ahead in a crowd­ed field

Lit­tle Alder Bio­Phar­ma­ceu­ti­cals $AL­DR has racked up a slate of pos­i­tive late-stage da­ta for its Phase III study of a new CGRP mi­graine drug, but it will like­ly have trou­ble stand­ing out from some of the gi­ant play­ers that are al­ready out front in the race to reg­u­la­tors.

Randy Schatz­man

Dubbed PROMISE 1, in­ves­ti­ga­tors es­tab­lished a base­line av­er­age of 8.6 month­ly mi­graines in its group of fre­quent episod­ic mi­graine suf­fer­ers. Alder’s quar­ter­ly-dosed 300 mg and 100 mg cut that rate by 4.3 and 3.9 days. But the place­bo arm al­so ex­pe­ri­enced a hefty 3.2 day im­prove­ment, leav­ing the biotech with a sta­tis­ti­cal­ly sig­nif­i­cant but un­re­mark­able hit on the pri­ma­ry end­point.

In­vestors didn’t re­spond well to the da­ta, ei­ther. The shares dropped a painful 24% in pre-mar­ket trad­ing.

The Both­ell, WA-based biotech did flag some high­lights, though, in­clud­ing a 100% re­sponse among 20% of the pa­tients, there was a sig­nif­i­cant drop ear­ly on in the eptinezum­ab arm for mi­graines and a third achieved a 75% re­duc­tion in mi­graines in weeks 4 through 12. There was not, though, a sig­nif­i­cant drop in the 75% re­duc­tion group over­all for the 100 mg dose.

Alder’s big promise is that its quar­ter­ly IV in­fu­sion ther­a­py can beat or match oth­er drugs which are more fre­quent­ly dosed, mak­ing it an eas­i­er al­ter­na­tive pre­ferred by pa­tients. And it has plans for self-ad­min­is­tra­tion that could al­so po­si­tion the biotech against ri­vals, notes Leerink’s Paul Mat­teis. He adds:

The “high rate of “su­per re­spon­ders” (75% and 100% re­duc­tions)…looks very com­pet­i­tive com­pared to phase III re­sults for oth­er an­ti-CGRPs. While the ap­proval of the IV – pend­ing da­ta from PROMISE2 – is most­ly de­risked, the re­sults raise the ques­tion of what AL­DR will do with its self-ad­min­is­tra­tion as the high­er 300mg dose ap­pears bet­ter than 100mg. One of the most im­pres­sive dat­a­points was the speed-of-on­set: >50% of eptinezum­ab-treat­ed pa­tients had no mi­graines on day two of the study ver­sus 37% on place­bo; this was sta­tis­ti­cal­ly sig­nif­i­cant.

But this is a field where a full line­up of ma­jor league drug de­vel­op­ers has been cheer­ing a se­ries of achieve­ments. Te­va just days ago lined up a 1.5-day ad­van­tage for fre­manezum­ab, putting it in a mix of re­sults post­ed with an im­prove­ment for these drugs that tends to hov­er around the 2-day mark. And it has re­sults for month­ly and quar­ter­ly dos­ing.

Re­searchers are al­ways quick to protest any tri­al com­par­isons that aren’t head-to-head, and pa­tients pop­u­la­tions and dos­ing aren’t an even match in the stud­ies. But pay­ers will al­so be ex­pect­ed to con­sid­er Eli Lil­ly’s 2-day ad­van­tage, or a Phase III out­come for Am­gen and No­var­tis that was quite sim­i­lar to Alder’s for 70 mg erenum­ab, the ther­a­py that is the fur­thest out front. Al­ler­gan al­so has high hopes for its oral ther­a­py in-li­censed from Mer­ck for $250 mil­lion up­front.

Alder al­so has a ways to go in com­plet­ing its Phase III pro­gram.

“These pos­i­tive re­sults, con­sis­tent with pre­vi­ous­ly re­port­ed eptinezum­ab stud­ies, sup­port the unique clin­i­cal pro­file of eptinezum­ab as a po­ten­tial first-of-its-kind in­fu­sion ther­a­py to pre­vent mi­graines,” says Randy Schatz­man. “En­roll­ment is on track for PROMISE 2, our sec­ond piv­otal Phase III study that fo­cus­es on chron­ic mi­graine, and we re­main on track to sub­mit our BLA with the U.S. Food and Drug Ad­min­is­tra­tion (FDA) in the sec­ond half of 2018.”

What’s clear is that no mat­ter how this race ul­ti­mate­ly pans out, mi­graine suf­fer­ers will soon have plen­ty to pick from for a new stan­dard of care in the field. And Alder re­mains a key play­er among the de­vel­op­ers out to make a ma­jor dif­fer­ence for pa­tients.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Matt Gline (L) and Pete Salzmann

UP­DAT­ED: Roivant bumps stake in Im­muno­vant with a $200M deal. But with M&A off the ta­ble, shares crater

Roivant has worked out a deal to pick up a chunk of stock in its majority-owned sub Immunovant $IMVT, but the stock buy falls far short of its much-discussed thoughts about buying out all of the 43% of shares it doesn’t already own.

Roivant, which recently inked a SPAC move to the market at a $7 billion-plus valuation, has forged a deal to boost its ownership in Immunovant by 6.3 points, ending with 63.8% of the biotech’s stock following a $200 million injection. That cash will bolster Immunovant’s cash reserves, giving it a $600 million war chest to fund a slate of late-stage studies for its big drug: the anti-FcRn antibody IMVT-1401.

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Sanofi preps a multi­bil­lion-dol­lar buy­out of an mR­NA pi­o­neer af­ter falling be­hind in the race for a Covid-19 jab — re­port

It looks like Sanofi CEO Paul Hudson is dead serious about his intention to vault directly into contention for the future of mRNA vaccines.

A year after paying Translate Bio a whopping $425 million in an upfront and equity payment to help guide the pharma giant to the promised land of mRNA vaccines for Covid-19, Sanofi is reportedly ready to close the deal with a buyout.

Translate’s stock $TBIO soared 78% after the market closed Monday. A spokesperson for Sanofi declined to comment on the report, telling Endpoints News that the company doesn’t comment on market rumors.

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Alan Hirzel, Abcam

Drug sup­pli­er Ab­cam brings a long­time col­lab­o­ra­tor in house as part of $340M buy­out pact

BioVision has supplied Abcam with research tools since 1999, and now the two are making it official as part of a merger unveiled Monday.

Abcam will buyout BioVision as part of a $340 million acquisition deal to bring aboard the supplier’s biochemical and cell-based assays for biological research, as well as recombinant proteins, antibodies and enzymes.

The deal will give Abcam control of BioVision’s portfolio and allow for both the expansion of research existing areas of focus such as oncology, neuroscience and epigenetics and preparation to expand into new products. As a part of the deal, Abcam will develop and supply products and services to NKY, the previous owner of BioVision and receive support for ongoing development and commercialization of in vitro diagnostic products.

Tib­so­vo clears an­oth­er hur­dle for Servi­er, but can it make Agios' old drug prof­itable?

When European regulators saw the data Agios used to win US approval for their AML drug Tibsovo, they sent the more than decade-old biotech back to the drawing board. A single, single-armed trial was not going to cut it.

On Monday, though, the drug’s new owners announced it had cleared a more rigorous study. In a randomized, Phase III trial of certain newly diagnosed patients, those who received a combination of Tibsovo and chemotherapy lived longer than those who received a combination of placebo and chemotherapy. Those patients also had higher response rates and complete remission rates.

UP­DAT­ED: Watch out Glax­o­SmithK­line: As­traZeneca's once-failed lu­pus drug is now ap­proved

Capping a roller coaster journey, AstraZeneca has steered its lupus drug anifrolumab across the finish line.

Saphnelo, as the antibody will be marketed, is the only treatment that’s been approved for systemic lupus erythematosus since GlaxoSmithKline’s Benlysta clinched an OK in 2011. The British drugmaker notes it’s also the first to target the type I interferon receptor.

Mirroring the population that the drug was tested on in late-stage trials, regulators sanctioned it for patients with moderate to severe cases who are already receiving standard therapy — setting up a launch planned for the end of August, according to Ruud Dobber, who’s in charge of AstraZeneca’s biopharmaceuticals business unit.

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Not all mR­NA vac­cines are cre­at­ed equal. Does it mat­ter?; Neu­ro is back; Pri­vate M&A af­fair; 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.

As part of our broader and deeper drive, Endpoints has been pairing webinars with our special reports to cover more angles on a given topic. In conjunction with Max Gelman’s neuroscience feature, Kyle Blankenship moderated an insightful panel to discuss where the field is headed. You can register to watch it on demand here.

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Bris­tol My­ers pulls lym­phoma in­di­ca­tion for Is­to­dax af­ter con­fir­ma­to­ry tri­al falls flat

Amid an industrywide review of cancer drugs with accelerated approval, Bristol Myers Squibb had to make the tough call last month to yank an approval for leading I/O drug Opdivo after flopping a confirmatory study. Now, a second Bristol Myers drug is on the chopping block.

Bristol Myers has pulled aging HDAC inhibitor Istodax’s indication in peripheral T cell lymphoma after a Phase III confirmatory study for the drug flopped on its progression-free survival endpoint, the drugmaker said Monday.

Rick Pazdur (via AACR)

FDA's on­col­o­gy head Rick Paz­dur de­fends the ac­cel­er­at­ed ap­proval path­way, claim­ing it is 'un­der at­tack'

The FDA is sounding the alarm over its accelerated approval pathway as backlash continues over the recent nod in favor of Biogen’s Alzheimer’s drug Aduhelm, and an ODAC meeting on six such approvals that could potentially be pulled from the market — two of which already have.

“Do you think accelerated approval is under attack? I do,” Rick Pazdur, head of FDA’s Oncology Center of Excellence, said at a Friends of Cancer Research webinar on Thursday.

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