FDA mo­tions Al­ny­lam's lumasir­an in­to a PhI­II short track, set­ting up a shot at an OK in '20

Al­ny­lam $AL­NY may be go­ing so­lo on the de­vel­op­ment of rare dis­ease drug lumasir­an af­ter Sanofi took a pass on its op­tion, but the FDA has come through with a ma­jor as­sist. The com­pa­ny an­nounced to­day that reg­u­la­tors have agreed on a Phase III study de­sign that would ac­cel­er­ate — should all go well — its jour­ney to ap­proval.

For the tri­al de­signed to test lumasir­an in the ul­tra-rare pri­ma­ry hy­per­ox­aluria type 1 (PH1), the new­ly reached align­ment al­lows Al­ny­lam to adopt a pri­ma­ry end­point based on a bio­mark­er: the re­duc­tion of uri­nary ox­alate at six months. The FDA has al­so sanc­tioned a study size of around 25 pa­tients with PH1.

Pritesh Gand­hi

The use of a bio­mark­er spot­lights the FDA’s will­ing­ness to let drug­mak­ers shoot for faster OKs, rather than forc­ing them to wait for da­ta on dis­ease pathol­o­gy (Al­ny­lam notes the bio­mark­er is “di­rect­ly linked to the patho­phys­i­ol­o­gy of PH1 and known to be well cor­re­lat­ed with dis­ease pro­gres­sion”).

The tri­al de­sign pact with the agency al­so marks an ad­vance for the late-stage pipeline at Al­ny­lam as it waits for an ex­pect­ed ap­proval of patisir­an, which will launch their first com­mer­cial op­er­a­tions in RNAi. This biotech has been through all the ups and downs of­ten seen with any new ap­proach to drug de­vel­op­ment. And it’s poised for some ma­jor changes.

With the study de­sign ham­mered out, Al­ny­lam ex­pects to start the PhI­II study in mid-2018, re­port topline re­sults in 2019 and, if pos­i­tive, sub­mit an NDA in ear­ly 2020.

“We are very pleased with the FDA’s shared sense of ur­gency to eval­u­ate the ef­fi­ca­cy and safe­ty of lumasir­an as a po­ten­tial ther­a­peu­tic op­tion for pa­tients as rapid­ly as pos­si­ble,” said Pritesh Gand­hi, gen­er­al man­ag­er of the lumasir­an pro­gram, in a state­ment.

Al­ny­lam is cur­rent­ly con­duct­ing a Phase I/II Part B study in 20 pa­tients. Pre­lim­i­nary re­sults, an­nounced last year, sug­gest that lumasir­an led to a mean max­i­mal re­duc­tion in uri­nary ox­alate of 66% in an un­blind­ed group of four pa­tients, and all of them achieved uri­nary ox­alate lev­els at or near the nor­mal range. Lumasir­an, an RNAi ther­a­peu­tic, is de­signed to “re­duce the he­pat­ic lev­els of the [gly­co­late ox­i­dase] en­zyme, there­by de­plet­ing the sub­strate nec­es­sary for ox­alate pro­duc­tion.” It was grant­ed a break­through ther­a­py des­ig­na­tion in March.

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.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

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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Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Anthony Coyle (Repertoire)

Flag­ship's merged biotech Reper­toire nets ex-Pfiz­er CSO An­tho­ny Coyle as R&D chief

Flagship is building a big-name C-suite at its new, $220 million merged biotech.

Repertoire Immune Medicines, which already boasts former Bioverativ chief John Cox as its CEO, announced yesterday that Anthony Coyle, the former Pfizer CSO and the founding CEO of Pandion, will join as their head of R&D.

“As we progress clinical trials for our multi-clonal T cell candidates in immuno-oncology, Tony’s deep expertise in cellular immunology and novel therapeutic development will help us achieve our vision of creating a new class of transformative medicines for patients,” Cox said in a statement.

Can a mag­net­ic cell ther­a­py re­place corneal trans­plan­ta­tion? As eight-year jour­ney leads to the clin­ic, two broth­ers un­veil bold vi­sion

Jeff Goldberg was getting acquainted with a brand new way to do corneal transplants when an even newer, even bolder idea hit him.

It was almost 10 years ago, and Goldberg was in his first faculty position at Bascom Palmer Eye Institute at the University of Miami. Scientists had developed a new way to do cornea transplants where instead of sewing a whole donor cornea — a decades-old practice — they were just engrafting the inner layer of cells.

News brief­ing: Tiny Vac­cinex's drug flops in PhII Hunt­ing­ton's tri­al, stock craters; Siol­ta nabs $30M Se­ries B to de­vel­op mi­cro­bio­me drug

Siolta Therapeutics, a microbiome company targeting allergic diseases, raked in a $30 million Series B to develop its lead candidate, STMC-103H. The drug, which has been FDA fast-tracked, is headed for proof-of-concept trials, according to the company. Its various indications include allergic asthma, food allergies, atopic dermatitis, allergic rhinitis, and allergy prevention.

The news comes just after the California-based biotech added a prominent biopharma veteran as an advisor: 20-year Gilead CEO John Martin. The biotech also gained Richard Shames as CMO, who came by way of Protagonist Therapeutics.

Embattled CDC director Robert Redfield (AP Images)

Covid-19 roundup: CDC ad­vi­so­ry com­mit­tee de­lays pri­or­i­ty dis­tri­b­u­tion vote; EU re­port­ed­ly in­dem­ni­fy­ing vac­cine mak­ers

A federal committee that advises the CDC was expected to hold a vote Tuesday on a plan regarding the distribution for initial doses of approved Covid-19 vaccines. But that vote has been scrapped.

The Advisory Committee on Immunization Practices, or ACIP, won’t be voting until the committee members learn more about which vaccines become available first, the Wall Street Journal reported. The vote could potentially wait until a specific vaccine is authorized before recommending how to dole out the first doses.