FDA drafts rec­om­men­da­tions for study­ing can­cer drugs in pa­tients with CNS metas­tases

The FDA on Wednes­day is­sued draft guid­ance pro­vid­ing rec­om­men­da­tions to drug­mak­ers on eval­u­at­ing can­cer drugs in pa­tients with cen­tral ner­vous sys­tem (CNS) metas­tases. FDA says the guid­ance is meant to in­form clin­i­cal tri­al de­signs to sup­port prod­uct la­bel­ing that de­scribes an­ti­tu­mor ac­tiv­i­ty of drugs or bi­o­log­ics in pa­tients with CNS metas­tases from sol­id tu­mors orig­i­nat­ing in oth­er parts of the body.

Richard Paz­dur

“There are few ef­fec­tive treat­ments for pa­tients with cen­tral ner­vous sys­tem (CNS) metas­tases — a type of can­cer that has spread from the orig­i­nal tu­mor to the CNS and is as­so­ci­at­ed with a high­er risk of death. In ad­di­tion, there are al­so few clin­i­cal tri­als test­ing ther­a­pies for CNS metas­tases. More at­ten­tion is war­rant­ed to ad­dress this un­met med­ical need,” said Richard Paz­dur, di­rec­tor of FDA’s On­col­o­gy Cen­ter of Ex­cel­lence.

When look­ing to en­roll pa­tients with brain metas­tases in clin­i­cal tri­als, FDA di­rects spon­sors to its re­cent­ly fi­nal­ized guid­ance, Can­cer Clin­i­cal Tri­al El­i­gi­bil­i­ty Cri­te­ria: Brain Metas­tases.

In the guid­ance, FDA ex­plains some of the chal­lenges present in eval­u­at­ing treat­ments for CNS metasta­t­ic dis­ease. “The po­ten­tial for ben­e­fit of a drug as as­sessed by tu­mor shrink­age of CNS le­sions is un­in­ter­pretable with­out in­for­ma­tion re­gard­ing tu­mor shrink­age at ex­tra-CNS dis­ease sites. Fur­ther­more, eval­u­a­tion of an­ti-tu­mor ac­tiv­i­ty, par­tic­u­lar­ly dura­bil­i­ty of tu­mor re­sponse in the CNS may not be at­trib­ut­able sole­ly to the in­ves­ti­ga­tion­al drug, as treat­ment would gen­er­al­ly be changed at the time of ex­tra CNS dis­ease pro­gres­sion in pa­tients with ev­i­dence of sta­ble or re­spond­ing CNS le­sions,” FDA writes.

FDA al­so notes that CNS dis­ease should not be eval­u­at­ed in iso­la­tion from metasta­t­ic dis­ease in the rest of the body. As such, FDA says that “ef­fi­ca­cy claims based on end­points mea­sur­ing CNS ac­tiv­i­ty alone may not be ap­pro­pri­ate.”

To de­ter­mine whether an ex­pe­dit­ed pro­gram for ther­a­pies with­out avail­able ther­a­peu­tic al­ter­na­tives, FDA says it con­sid­ers, “an avail­able ther­a­py for a metasta­t­ic sol­id tu­mor [to] be an avail­able ther­a­py for CNS metas­tases of that sol­id tu­mor, un­less oth­er­wise spec­i­fied in the la­bel­ing for that ther­a­py.”

When it comes to de­sign­ing clin­i­cal tri­als, FDA says spon­sors should take con­sid­er­a­tion of pri­or ther­a­pies sub­jects may have re­ceived. FDA notes that spon­sors should cap­ture in­for­ma­tion on all pri­or CNS-di­rect­ed treat­ments and that pro­to­cols should spec­i­fy an in­ter­val, typ­i­cal­ly of at least 12 weeks, be­tween com­ple­tion of CNS ra­di­a­tion ther­a­py and study en­try, “to al­low at­tri­bu­tion of treat­ment ef­fects to the study in­ter­ven­tion.”

Ad­di­tion­al­ly, pro­to­cols, “Should spec­i­fy ap­pro­pri­ate strat­i­fi­ca­tion fac­tors for ran­dom­iza­tion to min­i­mize bias based on pri­or ther­a­py(ies).”

FDA al­so pro­vides guid­ance on as­sess­ing CNS metas­tases, not­ing that mag­net­ic res­o­nance imag­ing (MRI) with gadolin­i­um con­trast is pre­ferred and that pro­to­cols should re­quire base­line imag­ing eval­u­a­tion of the CNS in all en­rolled pa­tients with CNS dis­ease. Oth­er rec­om­men­da­tions in­clude ap­ply­ing ac­cept­ed stan­dard re­sponse cri­te­ria for eval­u­at­ing CNS dis­ease and re­quir­ing on-study imag­ing as­sess­ments for CNS dis­ease at the same time points as those for ex­tra-CNS dis­ease.

As for end­points, FDA says the se­lec­tion of an ap­pro­pri­ate end­point will de­pend on the study pop­u­la­tion and whether the study is eval­u­at­ing on­ly pa­tients with CNS metas­tases. Some of the end­points FDA says may be con­sid­ered in­clude time-to-event end­points in ran­dom­ized con­trolled tri­als, over­all sur­vival or end­points based on tu­mor as­sess­ment such as over­all re­sponse rate or pro­gres­sion-free sur­vival.


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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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