Al­ny­lam nabs speedy re­view, set­ting up 3rd pos­si­ble ap­proval in 3 years

Af­ter near­ly two decades in the haze of pre­clin­i­cal and clin­i­cal de­vel­op­ment, things seem to be com­ing in­to fo­cus for Al­ny­lam Phar­ma­ceu­ti­cals.

Two years ago the com­pa­ny land­ed the first ap­proved drug for RNA in­ter­fer­ence (RNAi), a No­bel Prize-win­ning tech­nique dis­cov­ered in plants and pi­o­neered around the turn of the cen­tu­ry. Then last year, they land­ed an­oth­er ap­proval. Now, fresh off a mas­sive in­vest­ment from Black­stone, they’ve re­ceived an FDA pri­or­i­ty re­view des­ig­na­tion for a third ther­a­py, set­ting them up to po­ten­tial­ly nab three dif­fer­ent ap­provals in three con­sec­u­tive years.

The re­view vouch­er is for an RNAi drug called lumasir­an, for use in a rare dis­ease called pri­ma­ry hy­per­ox­aluria type 1, or PH1. The life-threat­en­ing dis­ease is caused by an over­pro­duc­tion of ox­alate, an end-prod­uct of me­tab­o­lism whose buildup can dam­age mul­ti­ple or­gans, start­ing with the kid­neys. Al­ny­lam’s RNAi drug low­ers ox­alate lev­els by si­lenc­ing the RNA se­quences for the en­zyme that makes it, gly­co­late ox­i­dase.

The FDA, which has al­so grant­ed the drug break­though ther­a­py sta­tus and a pe­di­atric rare dis­ease des­ig­na­tion, is sched­uled to rule on the drug by De­cem­ber 3. No ad­vi­so­ry com­mit­tee has been sched­uled.

For Al­ny­lam, a third ap­proval would be a key step in their march to­ward prof­itabil­i­ty. Black­stone in­vest­ed up-to $2 bil­lion in the com­pa­ny last month, in part in ex­change for Al­ny­lam’s share of roy­al­ties on a fourth RNAi drug, in­clisir­an — a po­ten­tial block­buster cho­les­terol in­jectable that has been sub­mit­ted to the FDA by No­var­tis but orig­i­nal­ly emerged at Al­ny­lam. The move was viewed by an­a­lysts as a key step to­wards mak­ing the com­pa­ny prof­itable. De­spite rev­enue from their first ap­proved drug, On­pat­tro, they lost near­ly a $1 bil­lion last year, as the R&D costs of their grow­ing clin­i­cal pro­grams swelled.

If ap­proved, lumasir­an will like­ly look sim­i­lar to Al­ny­lam’s first two ap­proved drugs: a pow­er­ful ther­a­py for a rare con­di­tion that comes at a high price. On­pat­tro, for a fa­tal con­di­tion called hered­i­tary transthyretin-me­di­at­ed amy­loi­do­sis, costs $450,000 per year. The com­pa­ny’s most re­cent­ly ap­proved drug, Givlaari, for a rare ge­net­ic con­di­tion called acute he­pat­ic por­phyr­ia, sells for $575,000.

In Phase III re­sults an­nounced last De­cem­ber, the drug met both the pri­ma­ry end­point — the re­duc­tion in base­line ox­alate over 3 to 6 months — and all six sec­ondary end­points.

Like the first two Al­ny­lam drugs, lumasir­an tar­gets gene ex­pres­sion in the liv­er. The or­gan, where the body fil­ters all for­eign sub­stances, has been the fore­most tar­get for RNA ther­a­peu­tics, and one of the key long-run­ning ques­tions about the tech­nol­o­gy is how well Al­ny­lam and oth­ers will be able to get their drugs to the rest of the body. Even in­clisir­an, the cho­les­terol drug, works by si­lenc­ing a gene, PC­SK9, that’s pre­dom­i­nant­ly ex­pressed in the liv­er.

An an­swer, though, may be com­ing soon. Al­ny­lam’s Covid-19 pro­gram will use an in­halant form of RNA, so that it can reach the ep­ithe­lial cells where Covid-19 takes root. That pro­gram is set to en­ter the clin­ic in col­lab­o­ra­tion with Vir Biotech­nol­o­gy by the end of the year.

Lumasir­an was in­clud­ed in the Al­ny­lam-Dicer­na cross-li­cens­ing deal ear­li­er this year, and Dicer­na will get roy­al­ties if it is ap­proved.

CDC’s Robert Redford, NIAID’s Anthony Fauci, Admiral Brett Giroir at HHS, and FDA’s Stephen Hahn prepare to testify at a House hearing on June 23 (Getty)

'Ex­treme­ly po­lit­i­cal' — Trump neuters FDA's at­tempt to strength­en vac­cine EUA, ques­tions need to length­en process

Stephen Hahn went before a Senate committee Wednesday and declared he’s fighting. “Every one of the decisions we have reached has been made by career FDA scientists based on science and data, not politics,” he exclaimed, adding that “FDA will not permit any pressure from anyone to change that. I will fight for science.”

A few hours later, he was undermined by President Donald Trump when a reporter asked if he was okay with stricter vaccine guidelines that the FDA was said to be cooking up. “That has to be approved by the White House. We may or may not approve it. That sounds like a political move,” he decided.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

CEO Markus Warmuth (Monte Rosa)

Monte Rosa rakes in $96M Se­ries B as it pre­pares 'mol­e­c­u­lar glue' plat­form for IND-en­abling stud­ies

About four months after completing an extension to its Series A, Monte Rosa Therapeutics is putting its next foot forward with another heap of cash.

The Boston-based biotech is back with $96 million in Series B financing with a goal to get its lead program ready for IND-enabling studies by the end of the year. Though Monte Rosa is keeping its specific target a secret for now, the company has been researching how to utilize its protein degradation technology in breast cancer and non-small cell lung cancer, among other areas.

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

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Jim Roberts and Brian Finrow (Lumen Bioscience)

With a $4M fed­er­al grant, Lu­men jumps in­to the Covid-19 treat­ment race

It’s been less than a month since Lumen Bioscience announced a $16 million Series B to engineer spirulina — a nutrient-packed super food — for diseases like traveler’s diarrhea, norovirus and C. difficile colitis. And now, the biotech has pulled in another $4 million to do the same for Covid-19.

The approach is quite similar to other gastrointestinal targets the company is pursuing, co-founders and Brian Finrow and Jim Roberts said. The Seattle-based company is working on a camelid antibody cocktail to combat GI infection common among Covid-19 patients. In a study published in the American Journal of Gastroenterology, a majority of Covid-19 patients showed GI and respiratory symptoms, and 25% had only GI symptoms.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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