John Maraganore (via Getty Images)

Al­ny­lam nears FDA fil­ing for 4th RNAi ther­a­py vutrisir­an af­ter late-stage da­ta back use in pro­tein mis­fold­ing dis­or­der

With three ap­proved RNAi ther­a­peu­tics al­ready on the mar­ket, Al­ny­lam has se­cured its place as the leader in that rare dis­ease-fo­cused field. Now, a fourth can­di­date is rapid­ly ap­proach­ing reg­u­la­tors’ desks, and Al­ny­lam hopes it will com­ple­ment an­oth­er of its drugs tar­get­ing a rare pro­tein mis­fold­ing dis­or­der.

On Thurs­day, Al­ny­lam un­veiled da­ta from its open-la­bel Phase III He­lios-A study show­ing vutrisir­an topped a his­tor­i­cal place­bo con­trol in re­duc­ing the symp­toms of polyneu­ropa­thy tied to transthyretin-me­di­at­ed (AT­TR) amy­loi­do­sis from base­line af­ter nine months of treat­ment. On sev­er­al sec­ondary end­points, in­clud­ing changes in qual­i­ty of life and pa­tient gait speed, vutrisir­an al­so beat out his­tor­i­cal place­bo.

The 164-pa­tient tri­al ran­dom­ized pa­tients 3:1 on ei­ther a once-quar­ter­ly, sub­cu­ta­neous 25mg dose of vutrisir­an for 18 months or 0.3mg of On­pat­tro (patisir­an), Al­ny­lam’s ap­proved RNAi ther­a­py for AT­TR. The study’s pri­ma­ry end­point judged pa­tients’ base­line changes against a his­tor­i­cal place­bo record­ed dur­ing On­pat­tro’s piv­otal Phase III Apol­lo study.

Al­ny­lam plans to sub­mit a new drug ap­pli­ca­tion for vutrisir­an with the FDA in ear­ly 2021 and stands ready to launch by ear­ly 2022. The com­pa­ny will then fol­low that with fil­ings in oth­er coun­tries, in­clud­ing Brazil and Japan, and then in the EU af­ter ob­tain­ing re­sults of the He­lios-A study’s 18-month analy­sis. That fil­ing could come lat­er this year.

Al­ny­lam CEO John Maraganore told End­points News the com­pa­ny de­cid­ed on the He­lios-A tri­al de­sign af­ter con­sul­ta­tion with the FDA, which de­cid­ed it was un­eth­i­cal to en­roll a new place­bo con­trol arm giv­en the dele­te­ri­ous ef­fects of the dis­ease and con­sis­tent place­bo da­ta from four oth­er late-stage tri­als Al­ny­lam has run in the dis­or­der.

“There is com­plete con­fi­dence that if a pa­tient’s left un­treat­ed with this dis­ease, they will in­ex­tri­ca­bly de­cline with a very de­fined rate of dis­abil­i­ty,” Maraganore said. “It is just ab­solute­ly un­eth­i­cal to do an­oth­er place­bo-con­trolled study.”

Al­ny­lam re­port­ed two deaths in the vutrisir­an arm of He­lios-A, both of which in­ves­ti­ga­tors didn’t tie to treat­ment. One of those pa­tients died of Covid-19 dur­ing treat­ment, Maraganore said, and an­oth­er died af­ter form­ing an il­i­ac artery oc­clu­sion fol­low­ing pneu­mo­nia. That pa­tient con­tract­ed pneu­mo­nia back in De­cem­ber 2019, and Maraganore said Al­ny­lam couldn’t con­firm whether it was ac­tu­al­ly an­oth­er nov­el coro­n­avirus case.

“Whether it was Covid or not, we don’t know,” he said.

There were al­so two cas­es of se­vere side ef­fects an in­ves­ti­ga­tor tied to vutrisir­an, Al­ny­lam said, which in­clud­ed dys­lipi­demia with uri­nary tract in­fec­tion. Maraganore said those side ef­fects are al­so com­mon for un­treat­ed pa­tients with AT­TR amy­loi­do­sis, and Al­ny­lam did not flag any new safe­ty con­cerns in the late-stage study.

As it an­gles for a sec­ond treat­ment tar­get­ing polyneu­ropa­thy tied to AT­TR, Al­ny­lam is al­so pur­su­ing both On­pat­tro and vutrisir­an in AT­TR with car­diomy­opa­thy, po­ten­tial­ly ex­pand­ing both drugs’ small pa­tient pools. As a good sign for the He­lios-B study for vutrisir­an in that in­di­ca­tion, the ther­a­py showed a sig­nif­i­cant ben­e­fit over place­bo in terms of re­duc­ing a key car­diac bio­mark­er known as NT-proB­NP. He­lios-B was ini­ti­at­ed in late 2019 and is cur­rent­ly en­rolling at sites around the world.

Maraganore tout­ed the first He­lios study’s da­ta as “spec­tac­u­lar” and as a sign of more to come.

“What this re­al­ly promis­es to do is re­al­ly sig­nif­i­cant­ly ex­pand our lead­er­ship and over­all op­por­tu­ni­ty in AT­TR space star­ing with polyneu­ropa­thy,” he said.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Janet Woodcock (AP Images)

End­points poll: Janet Wood­cock takes the (in­ter­im) helm at the FDA. And a large ma­jor­i­ty of our read­ers want her to stay there

It’s official: Janet Woodcock is now the acting chief of the FDA.

And — according to an Endpoints poll — most industry readers would like her to stay there, although a significant minority is strongly opposed.

To recap: Joe Biden is reportedly choosing between Woodcock and former deputy FDA commissioner Joshua Sharfstein as his nominee for the permanent position. Given their respective track records, the decision is set to determine the agency’s lodestar for years to come.

Endpoints News

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An Endpoints Zoom meeting; and the email header employees will see if your company is a Premium subscriber

What’s next for End­points — and how to sup­port our in­de­pen­dent bio­phar­ma news mis­sion

The firehose of biopharma news is gushing these days.

That’s why broader and deeper is the theme for 2021 at Endpoints. You can expect new coverage outside our core R&D focus, with deeper reporting in some key areas. When John Carroll and I launched Endpoints nearly five years ago, we were wading in waist-high waters. Now we’re a team of 25 full-time staffers (and growing) with plans to cover the flood of biopharma news, Endpoints-style.

Eli Lil­ly's an­ti­body cuts risk of Covid-19 by up to 80% among the most vul­ner­a­ble — but will it have a place next to vac­cines?

Eli Lilly says bamlanivimab lowered the risk of contracting symptomatic Covid-19 in a first-of-its-kind trial involving nursing home residents and staff, paving the way for a new option to protect against the virus.

But how big of an impact it might have, and what role it will play, at a time vaccines are being rolled out to the exact population it is targeting still remains unclear.

Among 965 participants in the study — all of whom tested negative for the coronavirus at baseline — the number of symptomatic cases reported in the bamlanivimab arm was 57% lower than that in the placebo arm (odds ratio 0.43, p=0.00021). In addition to that primary endpoint, all secondary endpoints reached statistical significance.

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Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by big set­back with a PhI­II fail­ure on NSCLC

Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein.

But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda.

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Northway Biotech's new manufacturing facility in Greater Boston

North­way Biotech sets up shop in Boston hub, look­ing to court more cus­tomers with bi­o­log­ics-fo­cused plant

Getting a foot in the door in Boston’s bustling biopharma hub is a rite of passage for many companies, but it comes with a steep price tag. Lithuanian CDMO Northway — now with a new moniker — will set up a new plant in close proximity, and it’s hoping its biologics focus will find a willing customer base.

Northway Biotech (formerly Northway Biotechpharma) on Wednesday held a virtual grand opening ceremony for its $40 million Waltham, MA facility — a 30,000 square-foot cGMP manufacturing and process development plant that will widely expand on the company’s previous capabilities.

News brief­ing: Five pub­lic biotechs, over 2 days, raise $883M from fresh of­fer­ings; Bel­gian biotech ex­pands Se­ries B fund­ing

The wave of biotech IPOs we’ve been seeing in the last few days underscores that the public markets remain one of the key channels for fresh investments in drug R&D. And that trend was in full view this week as a slate of biotechs nailed down hundreds of millions of dollars in fresh funds.

One of the big winners of the week is Editas $EDIT, which nailed $231 million to back its pioneering work on a gene editing platform. The biotech sold 3.5 million shares at $66 each.

With patent con­cerns loom­ing, Roche gets a new pri­or­i­ty re­view on block­buster IPF drug

Seven years after the FDA first approved Esbriet, the blockbuster Roche IPF drug is getting an expedited review for a second indication.

On Thursday, the agency gave Esbriet priority review for unclassified interstitial lung diseases, or forms of pulmonary inflammation and scarring that don’t fit easily into the over 200 known types of ILD. The move comes 10 months after Esbriet received breakthrough designation and sets Roche up for a decision by May.

Michelle McMurry-Heath, BIO CEO (BIO via YouTube)

BIO looks to re­struc­ture, lay­ing off staff amid chal­lenge to the trade org's nor­mal face-to-face style

The biopharma industry, on the whole, had a red-letter year in 2020 amid Covid-19, with fundraising at an all-time high and major players speeding vaccines ahead to approval. But for BIO, the industry’s leading trade organization, the pandemic has prompted a reconsideration of the game plan.

BIO will pivot to digital as the Covid-19 pandemic continues to rage, making “some staff reductions” as it looks to bring its roughly 37,000 in-person meetings each year to the web, the organization said Thursday.

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