10 ways to re­form the FDA's ac­cel­er­at­ed ap­proval path­way: ICER and MSKCC of­fer op­tions

The FDA’s top can­cer doc­tor Rick Paz­dur re­cent­ly called the FDA’s ac­cel­er­at­ed ap­proval path­way “un­der at­tack,” and three top drug pric­ing ex­perts from Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter and ICER are now call­ing the path­way “in flux, and many would say, in cri­sis.”

As the alarm bells sound, Paz­dur’s On­col­o­gy Cen­ter for Ex­cel­lence ini­ti­at­ed a re­view of the ac­cel­er­at­ed ap­proval path­way about a year ago, while more re­cent­ly, HHS’ In­spec­tor Gen­er­al said it al­so will re­view the path­way, fol­low­ing a quick ac­cel­er­at­ed OK for Bio­gen Alzheimer’s drug Aduhelm. The lat­ter re­view came in the face of con­flict­ing da­ta over whether the drug could ac­tu­al­ly slow pa­tients’ men­tal de­cline.

“There’s two ma­jor is­sues here: How do we re­move these drugs if their ac­cel­er­at­ed ap­proval stud­ies do not pan out, and the oth­er one is how the leg­is­la­tion is writ­ten,” Paz­dur said in a Pre­vi­sion Pol­i­cy we­bi­nar ear­li­er this sum­mer. At the time, he not­ed some dis­ap­point­ments from the re­cent mul­ti-day ODAC meet­ing in April on so-called “dan­gling” ac­cel­er­at­ed ap­provals, where a drug that fails a con­fir­ma­to­ry tri­al stays on the mar­ket.

The oth­er ma­jor is­sue is what should be con­sid­ered con­fir­ma­to­ry stud­ies, Paz­dur said, ques­tion­ing if it should just be ad­di­tion­al in­for­ma­tion from an on­go­ing, sin­gle-arm tri­al, or some­thing more.

“We’re caught in the mid­dle many times with on­col­o­gy prod­ucts of a sub­op­ti­mal de­vel­op­ment pro­gram yet a ter­rif­ic un­met need,” Paz­dur said. Over­all, how­ev­er, the ac­cel­er­at­ed path­way has “been very, very suc­cess­ful,” he added, not­ing, “but that doesn’t mean there isn’t room for im­prove­ment.”

Tak­ing that cue on what im­prove­ments can be made, An­na Kaltenboeck, health econ­o­mist and pol­i­cy re­searcher at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter, and ICER’s Aman­da Mehlman and Steven Pear­son pub­lished an ar­ti­cle in the Jour­nal of Com­par­a­tive Ef­fec­tive­ness Re­search on Wednes­day out­lin­ing 10 pos­si­ble ways to re­form the ac­cel­er­at­ed ap­proval path­way.

The re­searchers point to sev­en pol­i­cy re­forms that the FDA could make and an­oth­er three for pay­ers and the life sci­ence in­dus­try.

For the FDA, ICER and MSKCC, au­thors point to re­forms in the pre­mar­ket space, such as by strength­en­ing the se­lec­tion and use of sur­ro­gate end­points, de­vel­op­ing stan­dard­ized re­view tem­plates and re­quir­ing greater use of ran­dom­ized con­trolled tri­als, as well as oth­er rec­om­men­da­tions in the post­mar­ket space, such as cre­at­ing a new la­bel alert for ac­cel­er­at­ed drugs and bet­ter en­forc­ing the com­ple­tion of con­fir­ma­to­ry tri­als.

On sur­ro­gate end­points, the re­searchers call for FDA to re­lease for pub­lic com­ment a pre­lim­i­nary jus­ti­fi­ca­tion for why such an end­point could be used, in­clud­ing what cri­te­ria FDA has al­ready es­tab­lished to sup­port that end­point. The pub­lic com­ment pe­ri­od could al­low clin­i­cal ex­perts and oth­er stake­hold­ers with ex­per­tise in a par­tic­u­lar area to see the FDA’s think­ing and con­tribute to the fi­nal de­ci­sion on us­ing that end­point.

While RCTs are in­fea­si­ble in some sit­u­a­tions, such as with some very rare dis­eases, Kaltenboeck, Mehlman and Pear­son al­so say FDA “should adopt a for­mal shift in pos­ture to­ward re­quir­ing ran­dom­ized con­trolled tri­als.” This ap­proach could do more of the work up­front, ahead of an ac­cel­er­at­ed ap­proval, re­ly­ing less on the con­fir­ma­to­ry work.

Once a drug is mar­ket­ed un­der the ac­cel­er­at­ed path­way, the re­searchers say FDA could help pa­tients un­der­stand the un­con­firmed ben­e­fits of the drug by in­clud­ing a new vi­su­al for its la­bel, such as a yel­low tri­an­gle or a gray box.

On in­creas­ing the FDA’s en­force­ment of com­pa­nies that have dragged their feet in com­plet­ing con­fir­ma­to­ry tri­als, the re­searchers echo what Paz­dur men­tioned about how the path­way on­ly works if the FDA has the abil­i­ty to pull drugs when the fol­low-ups are mov­ing too slow or fail. One of the ma­jor is­sues with more en­force­ment, how­ev­er, is that it’s like­ly to trig­ger push­back from in­dus­try and pa­tient groups, rais­ing the risk that Con­gress would lean on the FDA to cool its jets on en­force­ment, as it did with the Right to Try leg­is­la­tion.

The re­searchers al­so pro­pose two more ideas that might re­quire Con­gres­sion­al ac­tion and are fur­ther re­moved from the sta­tus quo: Sun­set­ting ac­cel­er­at­ed ap­provals that lack con­fir­ma­to­ry ev­i­dence and cre­at­ing a sep­a­rate “safe­ty-on­ly” ap­proval path­way, which could po­ten­tial­ly put pa­tients at even more risk, es­pe­cial­ly if it waives pub­lic or pri­vate in­sur­ance cov­er­age re­quire­ments.

They write:

A law or reg­u­la­tion could be changed to au­to­mat­i­cal­ly with­draw mar­ket­ing au­tho­riza­tion for an ac­cel­er­at­ed ap­proval drug should its con­fir­ma­to­ry ev­i­dence not be avail­able for the FDA re­view by a pre­de­ter­mined date set at the time of ap­proval. This kind of for­mal ‘sun­set’ pol­i­cy would give the clear­est sig­nal to in­dus­try of what is re­quired, and pro­tect the FDA from pres­sure to change de­ci­sions when it makes them at its dis­cre­tion.

As far as poli­cies for life sci­ence com­pa­nies and pay­ers, the MSKCC and ICER re­searchers call to in­crease manda­to­ry fed­er­al re­bate lev­els un­til a drug shifts from ac­cel­er­at­ed to full ap­proval, use pric­ing to in­cen­tivize com­ple­tion of con­fir­ma­to­ry tri­als, and re­quire pay­ments un­der Medicare and Med­ic­aid for ac­cel­er­at­ed ap­proval drugs to be based on out­comes-based con­tracts.

For in­stance, the Med­ic­aid Drug Re­bate Pro­gram could be mod­i­fied for drugs with ac­cel­er­at­ed ap­proval, they note, to re­quire a high­er re­bate dur­ing the time be­tween ac­cel­er­at­ed and full ap­proval. The Med­ic­aid and CHIP Pay­ment and Ac­cess Com­mis­sion re­cent­ly vot­ed 16-1 to rec­om­mend to Con­gress that they in­crease Med­ic­aid re­bates for ac­cel­er­at­ed ap­proval drugs be­fore con­fir­ma­to­ry tri­als are com­plet­ed.

Image courtesy of The Janssen Pharmaceutical Companies of Johnson & Johnson.

Pro­tect­ing the glob­al phar­ma­ceu­ti­cal in­no­va­tion ecosys­tem – what’s at stake?

We are living in a new era of healthcare that is rapidly advancing progress impacting patient outcomes and experiences. We’ve seen a remarkable pace of transformational innovation, applied research, and advanced clinical development over the last decade.

Despite this tremendous progress, there is much more work to be done, and patients are counting on us – now more than ever – to continue that momentum. At the heart of our industry is a focus on developing and delivering medicines for some of the world’s most challenging diseases, including those that have few or no effective treatments today.

Roger Perl­mut­ter lines up deals, fresh fund­ing at Eikon; Sec­ond RSV vac­cine ap­proved; Sev­er­al biotechs flash­ing red; 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.

As you come back to our website this weekend for ASCO news, don’t forget to check out our updated event lineup at BIO, which will cover everything from the current state of VC investing in biotech to top pharma R&D chiefs discussing how to make pipeline decisions.

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Roger Perlmutter, Eikon Therapeutics CEO

Roger Perl­mut­ter builds Eikon's pipeline with deal-mak­ing flur­ry, rais­ing $106M more

Eikon Therapeutics announced three business development deals on Thursday, effectively dropping in a pipeline of cancer drugs alongside more than $100 million in fresh funding.

The Hayward, CA-based company has become one of biotech’s richest startups since its 2019 founding, having raised nearly $775 million. It’s developing a massive, automated research approach built around Nobel Prize-winning microscope science to peer inside cells and watch proteins in action. After its Series B last year, PitchBook reported a $3.02 billion valuation. And while CEO Roger Perlmutter declined to comment on that figure, he said its first tranche of nearly $106 million in Series C funding is a “meaningful step-up to our Series B valuation.”

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Grail’s blood test charts path for di­ag­nos­ing pa­tients sus­pect­ed of hav­ing can­cer in large study: #AS­CO23

Grail’s vision is simple but bold. The blood testing company has long held that people are often diagnosed with cancer too late. If seemingly healthy people were screened for early signs of the disease before symptoms appear, they may be able to get more effective treatments that nip cancer in the bud.

That premise is the basis of Grail’s commercial blood test, Galleri, which searches for the genetic fingerprints of cancer in the blood. The test, launched in 2021, reaped $55 million in sales last year, but now the company is setting its sights on a new market: patients suspected of having cancer due to symptoms such as abdominal pain, rectal bleeding or unexplained weight loss. Rather than administering expensive scans or conducting invasive biopsies right away, Grail hopes doctors will consider a simple blood test.

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Novartis headquarters in Basel, Switzerland (Kyle LaHucik for Endpoints News)

No­var­tis’ Kisqali pre­vents breast can­cer from com­ing back for longer — but can it best Eli Lil­ly’s Verzenio? #AS­CO23

CHICAGO — Novartis’ CDK4/6 inhibitor Kisqali helped early breast cancer patients stay cancer-free for longer after surgery, according to interim study results presented at ASCO.

In a Phase III study, Kisqali was added on top of endocrine therapy — the current standard treatment for early breast cancer patients. Kisqali reduced the risk of disease relapse by 25% compared with endocrine therapy alone in patients with Stage II or III HR-positive, HER2-negative breast cancer.

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GSK pro­motes rou­tine im­mu­niza­tions for adults amid post-pan­dem­ic vac­cine back­slide

GSK launched a new initiative on Thursday and committed up to $1 million in grant funding to improve adult routine vaccination rates.

While the pandemic spotlight was trained on the race for novel Covid-19 vaccines, other routine vaccination rates plummeted, raising concerns that missed doses may put children and even some adults at risk of preventable diseases such as measles or shingles. The World Health Organization last year reported the largest drop in childhood vaccinations in roughly three decades.

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Tammie Denyse speaks up about Black women and breast cancer inequity in Gilead's first TikTok campaign. (Gilead Sciences)

Gilead joins Tik­Tok with on­col­o­gy aware­ness cam­paign fea­tur­ing di­verse group of can­cer ad­vo­cates

Gilead Sciences is taking over the opening page on TikTok for the next two weeks. A Gilead-sponsored video, featuring cancer advocates talking about equity and other issues, will show up as the landing page, called the “For You” page, for millions of TikTok watchers.

The cancer awareness campaign will begin on Monday and run for two weeks, a Gilead spokesperson told Endpoints News. The TikTok ad debut is timed around the ASCO medical conference, but the work is aimed more broadly at healthcare professionals, as well as people touched by cancer and people interested in advancing Black and general health equity.

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Stephen MacMillan, Hologic CEO (Photo by Riccardo Savi/Getty Images for Concordia Summit)

Il­lu­mi­na names Ho­log­ic CEO as new board mem­ber and chair

Illumina’s board appointed two new members, including Hologic CEO Stephen MacMillan as the non-executive chair, a move that followed a proxy fight that saw shareholders oust the company’s board chair.

The DNA sequencing company also appointed Scott Ullem, the CFO of Edwards Lifesciences, to the board, according to a company statement.

Illumina’s plans to add two new board members came as Carl Icahn waged a board proxy campaign culminating with shareholders electing his candidate, Andrew Teno, over board chair John Thompson. Illumina CEO Francis deSouza survived a threat to his board seat by securing more than twice the shareholder votes than his challenger. Another Illumina candidate, Robert Epstein, was also elected and remained on the board.

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Catal­ent makes ad­di­tion­al lay­offs at In­di­ana fa­cil­i­ty

Contract manufacturer Catalent is making more staff cuts at one of its locations in the US amid dramatic corrective actions it’s been taking over the past few months.

In an email to Endpoints News, a Catalent spokesperson confirmed the company is making “a number of personnel changes” at a manufacturing facility in Bloomington, IN. While a specific number was not given to Endpoints, several local media outlets, including Indiana Public Media and the Bloomington Herald-Times, have put the number of layoffs at 150. No postings have been made to the Indiana Department of Workforce Development’s WARN notice.

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