Bio­gen spells out re­mark­able ef­fi­ca­cy da­ta in Alzheimer's for ad­u­canum­ab, but safe­ty threat per­sists

Saman­tha Budd Hae­ber­lein, Bio­gen

Shares of Bio­gen jumped Thurs­day af­ter­noon af­ter an up­dat­ed as­sess­ment of the re­mark­ably pos­i­tive da­ta they’ve been col­lect­ing from the PRIME study of their Alzheimer’s drug hope­ful ad­u­canum­ab was leaked among in­vestors and then quick­ly spread on­line.

Aside from the ker­fuf­fle over how the da­ta first be­gan to sur­face, a close look at the full set of re­sults re­vealed a sur­pris­ing­ly pos­i­tive read­out that will help ig­nite re­newed en­thu­si­asm for Bio­gen’s prospects in what is per­haps the tough­est field in R&D — though a big safe­ty is­sue re­mains a key con­cern.

Look­ing over the da­ta from 196 pa­tients, in­ves­ti­ga­tors re­port­ed that they tracked sig­nif­i­cant de­creas­es in amy­loid plaque bur­den in the brains of pa­tients tak­ing a titrat­ed 10 mg dose of the drug “dur­ing 12 months of treat­ment in ApoE ε4-pos­i­tive pa­tients with pro­dro­mal or mild AD com­pared with place­bo.” And they linked that to a clear and sig­nif­i­cant slow­ing of the dis­ease.

Bio­gen’s shares end­ed up 1.5% at the close, af­ter bounc­ing up and down as the da­ta were passed around. In pre-mar­ket trad­ing shares spiked 3.75%.

In­ves­ti­ga­tors were able to track a slow­ing in the de­cline among pa­tients tak­ing a titrat­ed dose of ad­u­canum­ab. And the most com­mon ad­verse ef­fect, ARIA, “ap­peared” to be re­duced among the titrat­ed drug arm com­pared to the high­er fixed dose among pa­tients with the ApoE4 gene, which may pre­dis­pose them to the dis­ease.

The slow­ing in the Clin­i­cal De­men­tia Rat­ing-Sum of Box­es (CDR-SB, which mea­sures cog­ni­tive and func­tion­al per­for­mance) scale was sta­tis­ti­cal­ly sig­nif­i­cant in the titrat­ed arm com­pared to the place­bo group. And the in­ves­ti­ga­tors say they felt the da­ta they had gath­ered sup­port­ed the de­sign of their Phase III study, which puts this drug to the piv­otal test.

There ap­peared to be a clear dose re­sponse to the drug, which is what in­ves­ti­ga­tors like to see.

In a re­lease is­sued late Thurs­day, Bio­gen spelled out the changes in both the CDR-SB and MMSE mea­sures, break­ing out the scores by dos­es com­pared to a place­bo. For the CDR-SB Group, the place­bo arm wors­ened by an av­er­age of 1.89 points at 54 points. That was close to the 1.69 point drop for the 1 mg group, but far worse than the 0.70 in the titra­tion arm. The 10 mg group had the best score of 0.63.

On the MMSE score, the place­bo arm wors­ened an av­er­age of 2.45 points, but that dropped to 0.55 in the 10 mg arm and 1.00 in the titra­tion arm.

ARIA, though, is clear­ly a per­sis­tent prob­lem. The in­ci­dence of ARIA-E in ApoE4 car­ri­ers in the fixed-dose arms was 5 per­cent in the 1 mg/kg and 3 mg/kg arms, 43 per­cent in the 6 mg/kg arm and 55 per­cent in the 10 mg/kg arm. The in­ci­dence of ARIA-E in ApoE4 car­ri­ers in the titra­tion arm was 35 per­cent.

Bri­an Sko­r­ney, Baird an­a­lyst

This is some of the most en­cour­ag­ing da­ta the Alzheimer’s field has seen in years, leav­ing ad­u­canum­ab as one of the top prospects now in late-stage de­vel­op­ment. While much more safe­ty and ef­fi­ca­cy da­ta re­main to be gath­ered in piv­otal stud­ies, its suc­cess at this stage marks a po­ten­tial turn­ing point, which could be rich­ly re­ward­ed by a mar­ket des­per­ate for an ef­fec­tive ther­a­py, es­pe­cial­ly so soon af­ter Eli Lily’s so­la flopped.

“Both ab­stracts high­light sig­nif­i­cant de­clines in plaque bur­den and as­so­ci­at­ed ben­e­fits in terms of the rate of clin­i­cal de­cline, with the titra­tion co­hort show­ing a stat sig ben­e­fit on CDR-SB com­pared to place­bo at 12 months,” not­ed Bri­an Sko­r­ney, who was en­cour­aged by the ex­ten­sion da­ta. He added:

 Of the 165/196 pa­tients in the PRIME study on a fixed dose, 91 were evalu­able out to 24 months. Pa­tients switched from place­bo to ad­u­canum­ab did show de­clines in plaque bur­den and slow­er rates of cog­ni­tive/func­tion­al de­cline. Pa­tients in the 10mg/kg and 6mg/kg dose groups re­main­ing on drug saw con­tin­ued ben­e­fit out to 24 months and an even more sig­nif­i­cant re­sponse than those who were switched on­to drug af­ter place­bo. There were no new cas­es of ARIA for those con­tin­u­ing on ad­u­canum­ab in the LTE. The one year fol­low up should be in­ter­pret­ed with cau­tion as pa­tients know they are on treat­ment and the clin­i­cal mea­sure­ments are sub­ject to high vari­abil­i­ty.

Ad­u­canum­ab is a crit­i­cal­ly im­por­tant drug for Bio­gen, which has ex­pe­ri­enced a se­ries of pipeline ups and downs as its block­buster Tec­fidera has be­gun to wane on the big mul­ti­ple scle­ro­sis mar­ket.

“The da­ta at CTAD sup­port the pos­i­tive re­sults we have seen in our Phase 1b study of ad­u­canum­ab, and they pro­vide in­sight in­to the ob­served ef­fects in pa­tients treat­ed for up to two years,” said Saman­tha Budd Hae­ber­lein, vice pres­i­dent, clin­i­cal de­vel­op­ment at Bio­gen. “We are com­mit­ted to ad­vanc­ing our glob­al Phase 3 pro­gram for ad­u­canum­ab as well as the sci­en­tif­ic un­der­stand­ing of Alzheimer’s dis­ease so we can help iden­ti­fy a treat­ment for the many peo­ple af­fect­ed by this ter­ri­ble dis­ease.”

https://twit­ter.com/Arm­strong­Drew/sta­tus/806952994855997440

Hal Barron, GSK

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Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:
I think that culture, to some extent, is as hard, in fact even harder, than doing the science.
GSK has had one of the most moribund R&D groups in Big Pharma for years. They proved over and over again that they were very slow to fail, while often sticking with programs with limited commercial upside in an effort to find something that worked. An earlier attempt to prod some changes with “biotech-like” research groups executive dedicated to its pipeline assets was a bust.

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Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

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Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

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Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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Chas­ing Roche's ag­ing block­buster fran­chise, Am­gen/Al­ler­gan roll out Avastin, Her­ceptin knock­offs at dis­count

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Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.

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