FDA commissioner Rob Califf (AP Photo/Jose Luis Magana)

Su­per-speedy can­cer drug re­views: FDA un­veils new draft guid­ance to help spon­sors ap­ply

How does a can­cer drug cross the FDA fin­ish line 3-5 months be­fore its PDU­FA date? That’s where the Re­al-Time On­col­o­gy Re­view comes in.

For the last five years, FDA’s On­col­o­gy Cen­ter of Ex­cel­lence un­der Rick Paz­dur has been qui­et­ly tapped in­to RTOR to al­low spon­sors to pro­vide even ear­li­er, seg­ment­ed sub­mis­sions of crit­i­cal ef­fi­ca­cy and safe­ty da­ta, there­by en­abling these faster eval­u­a­tions of ap­pli­ca­tions.

On Fri­day, OCE pro­vid­ed its first draft guid­ance on the RTOR pro­gram, ex­plain­ing how spon­sors can ap­ply, what to sub­mit if ac­cept­ed, and how RTOR is dif­fer­ent from rolling re­views, in that rolling re­views re­quire com­plete sec­tions (e.g., the com­plete clin­i­cal mod­ule) to be sub­mit­ted pri­or to a com­plete ap­pli­ca­tion sub­mis­sion.

“At the time top-line re­sults of a piv­otal tri­al(s) are avail­able and the data­base has been locked, an ap­pli­cant may ap­ply for re­view un­der RTOR by sub­mit­ting a re­quest via email,” the agency ex­plains. “The ap­pli­cant should in­clude their top-line re­sults and a writ­ten jus­ti­fi­ca­tion ex­plain­ing how their ap­pli­ca­tion demon­strates that it is ap­pro­pri­ate.”

Gen­er­al­ly, about 20 busi­ness days lat­er, the FDA re­view di­vi­sion will de­cide if an ap­pli­ca­tion can be ac­cept­ed.

While many of the drugs that have gone through RTOR so far have shaved sig­nif­i­cant time off their PDU­FA dates, the FDA al­so makes clear in Fri­day’s draft, that “this may not be fea­si­ble for all ap­pli­ca­tions due to spe­cif­ic is­sues that may be iden­ti­fied with the ap­pli­ca­tion or over­all work­load con­sid­er­a­tions.”

Gener­ic Drug­mak­ers and CRLs

An­oth­er hot-but­ton is­sue for the agency is the fact that gener­ic drugs of­ten go through mul­ti­ple cy­cles of re­views be­fore win­ning ap­proval.

To help com­bat these long cy­cles of CRLs and re-sub­mis­sions, the agency on Fri­day re­leased fi­nal guid­ance ex­plain­ing how if an AN­DA ap­pli­cant fails to ful­ly ad­dress all de­fi­cien­cies iden­ti­fied in a CRL, “with­in 1 year af­ter is­suance of the CRL (or take ei­ther of the oth­er two ac­tions pre­scribed by reg­u­la­tion and that are de­scribed above), FDA may con­sid­er this fail­ure to be a re­quest by the ap­pli­cant to with­draw the AN­DA.”

As far as changes from the draft is­sued on Sep­tem­ber 29, 2020, the agency said:

Changes from the draft to the fi­nal guid­ance in­clude adding an ap­pen­dix that pro­vides [nine] ex­am­ples of fac­tors that FDA could con­sid­er as the ba­sis for con­clud­ing that an ap­pli­cant’s re­quest for an ex­ten­sion of time to re­spond to a CRL is rea­son­able. In ad­di­tion, ed­i­to­r­i­al changes were made to im­prove clar­i­ty.

Re­mote Reg­u­la­to­ry As­sess­ments Out­side the Pan­dem­ic

The agency on Fri­day al­so is­sued a new Q&A-based draft guid­ance on re­mote reg­u­la­to­ry as­sess­ments, which have been an im­por­tant re­source for the agency dur­ing the pan­dem­ic, and will con­tin­ue to be of use af­ter the pan­dem­ic.

While the agency ex­plains how the FDA does not con­sid­er an RRA to sat­is­fy the le­gal re­quire­ments of what an in­spec­tion is (i.e. in-per­son as­sess­ment of a fa­cil­i­ty), it says they are still valu­able, par­tic­u­lar­ly as FDA has used them to help with ap­proval de­ci­sions, ver­i­fy cor­rec­tive ac­tions for es­tab­lish­ments with an ac­cept­able com­pli­ance sta­tus, and gain com­pli­ance in­sight in­to es­tab­lish­ments that FDA has been un­able to in­spect.

“The Agency be­lieves that FDA’s use of both vol­un­tary and manda­to­ry RRAs, as ap­plic­a­ble, for all types of FDA-reg­u­lat­ed prod­ucts is in the in­ter­est of the pub­lic health, and the Agency is is­su­ing this guid­ance to pro­vide fur­ther trans­paren­cy to stake­hold­ers about the cir­cum­stances in which RRAs may be used both dur­ing and be­yond the COVID-19 pan­dem­ic and pro­mote greater con­sis­ten­cy in the way RRAs are con­duct­ed,” the draft says.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Land­mark Amy­lyx OK spurs de­bate; Some... pos­i­tive? Alzheimer's da­ta; Can­cer tri­al bot­tle­neck; Sanofi's CRISPR bet; 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.

After brief stops in Paris and Boston, John Carroll and the Endpoints crew are staying on the road in October with their return for a live/streaming EUBIO22 in London. The hybrid event fireside chats and panels on mRNA, oncology and the crazy public market. We hope you can join him there.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Up­dat­ed: Al­ny­lam re­in­forces APOL­LO-B patisir­an da­ta be­fore head­ing to the FDA

Weeks after uncorking some mostly positive data for patisiran in transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, Alnylam is bolstering its package with new exploratory and subgroup data before shipping it off to regulators.

The RNAi drug maintained “generally consistent” benefits in efficacy and quality of life across several prespecified subgroups at month 12, Alnylam announced on Friday afternoon, including age, baseline tafamidis use, ATTR amyloidosis type, baseline six-minute walk test score and others.

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#AAO22: J&J’s first look at com­mon eye dis­ease port­fo­lio pads the case for PhII of gene ther­a­py

CHICAGO — While the later-stage drug developers in the geographic atrophy field are near the finish line, Johnson & Johnson’s Janssen is taking a more deliberate route, with a treatment that it hopes to be a one-time fix.

The Big Pharma will take its Hemera Biosciences-acquired gene therapy into a Phase II study later this year in patients with GA, a common form of age-related macular degeneration that impacts about five million people worldwide. To get there, Janssen touted early-stage safety data at the American Academy of Ophthalmology annual conference Saturday morning, half a day after competitors Apellis and Iveric Bio revealed their own more-detailed Phase III analyses.

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Jerome Durso, Intercept Pharmaceuticals CEO

In­ter­cep­t's OCA fails a PhI­II NASH tri­al, rais­ing fresh doubts about its years­long quest for an OK

Intercept Pharmaceuticals has run into another big setback in its yearslong quest to win an approval for OCA in NASH. The biotech put out word Friday morning that its Phase III REVERSE study failed the primary endpoint for the liver disease, sending its share price into a tailspin.

There was no significant improvement in fibrosis among the patients suffering from cirrhosis who were treated with obeticholic acid, with investigators hunting for a minimum 1-stage histological improvement in the disease after 18 months of therapy.

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Bo Cumbo, new Solid Bio CEO

Sol­id Bio gets a new CEO, $75M cash and drops lead drug as big in­vestors ju­ry-rig a merg­er deal

Three months after Endpoints News broke the story that gene therapy outfit AavantiBio had gutted its CMC group in a reorganization, the biotech’s CEO has helped engineer a merger with struggling penny stock player Solid Bio. And he’s going to remain in charge of the combined operation, as Solid founder Ilan Ganot steps aside.

The merger news this morning features some high-profile investors.

Perceptive Advisors, RA Capital Management and Bain Capital Life Sciences are leading a $75 million raise to add to the pool of cash Solid will have after the tie-up. That will leave Solid $215 million in cash as Bain’s Adam Koppel jumps on the board — enough to pay for ops and get through some key data milestones on their way into 2025.

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