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.

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

An NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

'Xeno­trans­plan­ta­tion is com­ing': New NE­JM pa­per gives de­tailed look in­to 2 pig-to-hu­man kid­ney trans­plant cas­es

The thymokidney is a curious organ, if you could call it that. It’s a sort of Frankensteinian creation — a system of pig thymus embedded underneath the outer layer of a pig’s kidney, made for human transplantation.

In the first case of pig-to-human xenotransplantation of a kidney into a brain-dead patient, the thymokidney quietly featured front and center.

In that experiment, which took place in September of last year, NYU researchers led by Robert Montgomery sutured a pig thymokidney onto the leg of a brain-dead 66-year-old woman. That case was widely reported on by a horde of major media outlets, including the New York Times, the BBC, and an in-depth feature by USA Today.

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Vlad Coric, Biohaven CEO

UP­DAT­ED: Fresh off $11.6B sale to Pfiz­er, New Bio­haven hits Phase III set­back just weeks af­ter Vlad Coric chalked up promise

When Pfizer bought up Biohaven’s migraine portfolio in the largest M&A deal of the year earlier this month, Biohaven CEO Vlad Coric promised the rest of the pipeline, which will live on under the umbrella of New Biohaven, still has a lot to offer. But that vision took a dent Monday as the drugmaker revealed it’s once again flopped on troriluzole.

The glutamate regulator failed to meet the primary endpoint on a Phase III study in patients with spinocerebellar ataxia, an inherited disorder that impairs a person’s ability to walk, speak and swallow. SCA can also lead to premature death.

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Mod­er­na seeks to dis­miss Al­ny­lam suit over Covid-19 vac­cine com­po­nent, claim­ing wrong venue

RNAi therapeutics juggernaut Alnylam Pharmaceuticals made a splash in March when it sued and sought money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which Alnylam claims have been integral to the way both companies’ mRNA-based Covid-19 vaccines work.

But now, Moderna lawyers are firing back, telling the same Delaware district court that Alnylam’s claims can only proceed against the US government in the Court of Federal Claims because of the way the company’s contract is set up with the US government. The US has spent almost $10 billion on Moderna’s Covid-19 vaccine so far.

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Cracks in the fa­cade: Is phar­ma's pan­dem­ic ‘feel good fac­tor’ wan­ing?

The discordant effects of the Covid-19 pandemic on pharma reputation continues. While the overall industry still retains a respectable halo from its Covid-19 quick response and leadership, a new patient group study reveals a different story emerging in the details.

On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

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Saqib Islam, SpringWorks CEO

Pfiz­er spin­out Spring­Works will ship its first drug to the FDA be­fore year’s end with PhI­II win

SpringWorks Therapeutics thinks it has cemented the backbone for its first “pipeline-in-a-product” oncology treatment and will send it to the FDA before the clock strikes 2023 with a Phase III win on Tuesday.

The oral gamma secretase inhibitor, dubbed nirogacestat, beat placebo on the primary goal of progression-free survival in adults with progressing desmoid tumors.

The soft-tissue tumors can lead to long-lasting pain, disfigurement and amputation, and there are currently no approved meds for the rare oncology indication. The tumors typically impact patients aged 20 to 44 years old and disproportionately affect women at rates 2 to 3 times higher, with up to a total of 1,650 new cases diagnosed in the US annually, according to SpringWorks.

Robert Califf (Michael Brochstein/Sipa USA via AP Images)

House Re­pub­li­cans at­tack Chi­na-on­ly da­ta in FDA sub­mis­sions, seek new in­ves­ti­ga­tion in­to re­search in­spec­tions

Three Republican representatives are calling on the FDA to take a closer look at the applications including only clinical data from China.

The letter to FDA commissioner Rob Califf late last week comes as the agency recently rejected Eli Lilly’s anti-PD-1 antibody, which attempted to bring China-only data but ran into a bruising adcomm that may crush the hopes of any other companies looking to bring cheaper follow-ons based only on Chinese data.

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