Poised to launch its first mar­ket­ing ef­fort, Al­ny­lam makes a big leap in­to CNS dis­eases and Alzheimer's

With its lead RNAi drug poised for an his­toric ap­proval, Al­ny­lam $AL­NY is now lay­ing plans to cre­ate a pipeline of CNS drugs that will tar­get some of the tough­est dis­eases that face re­searchers to­day — in­clud­ing Alzheimer’s, the Night King of dis­eases.

Kevin Fitzger­ald

Al­ny­lam re­searchers are fol­low­ing up on a ro­dent study where they say they were able to de­liv­er a small in­ter­fer­ing RNA drug — or siR­NA —in­to the brain and spinal cord area. Us­ing in­trathe­cal in­jec­tion — cir­cum­vent­ing the blood-brain bar­ri­er — the biotech says that they were able to durably si­lence a dis­ease tar­get gene tran­script, of­fer­ing proof of prin­ci­ple ev­i­dence that they could suc­ceed where a long queue of con­tenders have failed.

Us­ing new tech­nol­o­gy, Al­ny­lam says the plan now is to se­lect its first CNS can­di­date lat­er this year, with a grow­ing ef­fort to go af­ter a string of tough-to-beat dis­eases, in­clud­ing Alzheimer’s, Hunt­ing­ton’s, and Parkin­son’s.

“We have now ap­plied our learn­ings, in­clud­ing ad­di­tion­al chem­istry ad­vances, to en­able de­liv­ery of siR­NAs be­yond the liv­er to the CNS, where there are a large num­ber of un­met needs well suit­ed for RNAi ther­a­peu­tics. As we be­gin to ad­vance our CNS pipeline, ini­tial ef­forts are fo­cused on ge­net­i­cal­ly val­i­dat­ed CNS tar­gets, use of bio­mark­ers for ini­tial proof-of-con­cept, and dis­ease set­tings with high un­met need and a de­fin­able path to reg­u­la­to­ry ap­proval and pa­tient ac­cess,” said Kevin Fitzger­ald, the se­nior VP of re­search at Al­ny­lam. 

Alzheimer’s in par­tic­u­lar has proven to be the tough­est tar­get in bio­phar­ma. Mer­ck’s re­cent fail­ure with a BACE1 in­hibitor led the phar­ma gi­ant to con­clude that that ap­proach — elim­i­nat­ing the flow of amy­loid be­ta in­to the brain — will like­ly not work in symp­to­matic pa­tients. Their re­searchers al­so con­ced­ed that the whole amy­loid be­ta the­o­ry could be noth­ing but a fic­tion that drove bil­lions of dol­lars of mis­spent re­search in­vest­ments.

The fo­cus now has shift­ed more to­ward pre-symp­to­matic pa­tients as well as com­bi­na­tion ther­a­pies go­ing af­ter more than one tar­get at once. And the FDA has in­di­cat­ed its will­ing­ness to pro­vide new guide­lines that fo­cus more on bio­mark­ers of the dis­ease to prove a drug’s abil­i­ty to dri­ve im­proved cog­ni­tion for pa­tients.

While a host of ma­jor play­ers like Pfiz­er and As­traZeneca and GSK have re­treat­ed from the field in the wake of mul­ti­ple fail­ures, leav­ing few or no projects in their wake, new play­ers like Cel­gene and the start­up De­nali have been get­ting in­to the Alzheimer’s are­na. You can now in­clude one more big play­er which plans to make a dif­fer­ence.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'


Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

Susan Galbraith speaking at Endpoints News' virtual EUBIO21 summit

Imfinzi/treme­li­mum­ab com­bo scores As­traZeneca an­oth­er OS win — this time in liv­er can­cer

Is the tide turning on AstraZeneca’s battered PD-L1/CTLA4 combo?

A single priming dose of the experimental tremelimumab, followed by Imfinzi every four weeks, beat Nexavar (sorafenib) in helping a group of liver cancer patients live longer in a Phase III study, the company reported, meeting the primary endpoint.

Specifically, the two drugs extended overall survival for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy and were not eligible for localized treatment.

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FDA+ roundup: Marks on Wood­cock­'s tenure as act­ing com­mis­sion­er; FDA lead­ers of­fer per­spec­tive on bar­ri­ers to di­ver­si­ty in re­search

CBER director Peter Marks praised Janet Woodcock’s work as acting FDA commissioner, and while noting that Biden needs to nominate someone to fill the role permanently by Nov. 16, he said he has “no idea” when that actually might occur.

“Dr. Woodcock has been at the agency for over three decades and she, during that time, has proven herself to be a remarkably capable manager,” Marks said at the Alliance for Regenerative Medicine’s meeting Tuesday. “And she’s been managing as if she’s commissioner, unlike some previous acting [commissioners] who are afraid to actually do things. She doesn’t appear to be afraid to do things. I have not felt any different now from when we had a commissioner in place,” he added.

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FDA ad­comm votes unan­i­mous­ly in sup­port of a J&J Covid-19 boost­er two months af­ter one-dose shot

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Friday voted 19-0 in favor of authorizing a second shot of J&J’s Covid-19 vaccine to follow at least two months after the initial dose.

Regulators don’t have to follow VRBPAC’s recommendation, but they almost always do. Considering that the CDC’s advisory committee has already been set to review the expanded EUA, VRBPAC’s recommendation is likely to be adopted.