Tech glitch­es over­shad­ow FDA on­col­o­gy ad­comm as a sol­id ma­jor­i­ty of ad­vis­ers vote to keep Roche's Tecen­triq in mTNBC

Kick­ing off three days of re­ex­am­in­ing an­ti-PD(L)-1 ac­cel­er­at­ed ap­provals, the FDA’s On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee start­ed slow­ly on Tues­day. Af­ter a more than hour-long tech­ni­cal de­lay, mem­bers vot­ed 7-2 to keep alive the ac­cel­er­at­ed ap­proval for Genen­tech’s Tecen­triq (ate­zolizum­ab) plus Abrax­ane (nab-pa­cli­tax­el) in metasta­t­ic triple neg­a­tive breast can­cer (mTNBC) while ad­di­tion­al con­fir­ma­to­ry tri­als are on­go­ing.

But tech­ni­cal glitch­es at the hear­ing kept dis­cus­sions among the com­mit­tee’s can­cer ex­perts to on­ly a few ques­tions for Genen­tech, and the au­dio cut out be­fore the com­mit­tee mem­bers of­fered any of their typ­i­cal ex­pla­na­tions af­ter their votes.

Triple-neg­a­tive breast can­cer (TNBC) is no­to­ri­ous­ly dif­fi­cult to treat, rep­re­sent­ing 10-20% of breast can­cers, with a me­di­an sur­vival af­ter di­ag­no­sis of just 12 to 18 months and a 5-year sur­vival rate of 15%, ex­plained Char­lie Fuchs, a Yale can­cer spe­cial­ist who joined Roche in Jan­u­ary.

The good: With lim­it­ed oth­er treat­ment op­tions, Tecen­triq ini­tial­ly won its ac­cel­er­at­ed ap­proval in com­bi­na­tion with nab-pa­cli­tax­el for adult pa­tients with mTNBC whose tu­mors ex­press PD-L1 in March 2019 based on a me­di­an pro­gres­sion-free sur­vival (PFS) of 7.4 months, which com­pared with 4.8 months for those on place­bo in com­bo with nab-pa­cli­tax­el.

The bad: The con­fir­ma­to­ry tri­al did not pan out, and even showed a wor­ri­some sign as the place­bo out­per­formed the treat­ment com­bo in terms of over­all sur­vival.

Laleh Amiri-Ko­rdestani, di­vi­sion di­rec­tor at the Of­fice of On­co­log­ic Dis­eases, pre­sent­ed for the FDA on Tues­day and al­so not­ed that the over­all sur­vival re­sults in the ini­tial tri­al (on which the ac­cel­er­at­ed ap­proval is based) may be due to chance alone, and that the ben­e­fit seen in the first tri­al was not cor­rob­o­rat­ed in a sim­i­lar pop­u­la­tion in the con­fir­ma­to­ry tri­al.

The ug­ly: She al­so called the over­all sur­vival re­sults in the con­fir­ma­to­ry tri­al “con­cern­ing.” Those re­sults led to an alert from the agency and a la­bel up­date in De­cem­ber be­cause of the “pos­si­bil­i­ty of detri­ment” in over­all sur­vival.

Pre­sent­ing for Genen­tech, Steve Chui, glob­al de­vel­op­ment lead in on­col­o­gy, spelled out both the ben­e­fit from the ini­tial tri­al and how the con­fir­ma­to­ry tri­al did not show a PFS ben­e­fit. He al­so ex­plained how the re­sults from the con­fir­ma­to­ry tri­al showed 101 of those on place­bo and pa­cli­tax­el had a me­di­an of 28.3 months of over­all sur­vival, com­pared with 22.1 months for 191 of those on ate­zolizum­ab and pa­cli­tax­el.

Look­ing to the fu­ture, Chui point­ed to con­ver­sa­tions from De­cem­ber with FDA on oth­er pos­si­ble con­fir­ma­to­ry tri­als, in­clud­ing one that would use a dif­fer­ent type of chemo along with Tecen­triq in about 570 mTNBC pa­tients, which is ex­pect­ed to see re­sults in 2023. Oth­er tri­als pro­posed won’t read out un­til 2023 or 2024.

The FDA said in its brief­ing doc­u­ments that “it is not yet clear which of these tri­als are suf­fi­cient­ly de­signed to ad­e­quate­ly con­firm ben­e­fit,” and ad­comm pan­elists ques­tioned why one of the tri­als would use dif­fer­ent chemother­a­pies if it’s a con­fir­ma­to­ry tri­al for Tecen­triq and nab-pa­cli­tax­el. But the ma­jor­i­ty of mem­bers still vot­ed to keep the in­di­ca­tion un­der an ac­cel­er­at­ed ap­proval.

Pri­or to the dis­cus­sion of ate­zolizum­ab, Ju­lia Beaver, chief of med­ical on­col­o­gy at FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, opened the meet­ing by ex­plain­ing how ac­cel­er­at­ed ap­provals on­ly need to be “rea­son­ably like­ly to pre­dict clin­i­cal ben­e­fit,” and that of the 151 ac­cel­er­at­ed ap­provals for on­col­o­gy drugs, 35 have been for PD-(L)1 an­ti­bod­ies, in­clud­ing the three un­der scruti­ny this week, and a to­tal of 10 have been with­drawn.

Those with­drawals have come as the treat­ment land­scape may have changed or be­cause fol­low-up tri­als have failed to con­firm ben­e­fits.

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Dave Marek, Myovant CEO

My­ovant board balks as ma­jor­i­ty own­er Sum­it­o­mo swoops in with a $2.5B deal to buy them out

Three years after Sumitomo scooped up Roivant’s 46% stake in the publicly traded Myovant $MYOV as part of a 5-company, $3 billion deal, they’re coming back for the whole thing.

But these other investors at Myovant want more than what the Japanese pharma company is currently offering to pay at this stage.

Sumitomo is bidding $22.75 a share for the outstanding stock, which now represents 48% of the company after Sumitomo bumped its ownership since the original deal with Roivant. Myovant, however, created a special committee on the board, and they’re shaking their heads over the offer.

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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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Big Phar­ma heavy­weights seek tweaks to FDA's clin­i­cal out­come as­sess­ment guid­ance

Pfizer, GSK, Janssen, Regeneron, Boehringer Ingelheim and at least a half dozen other companies are calling on the FDA to provide significantly more clarity in its draft guidance from this summer on clinical outcome assessments, which are a type of patient experience.

The draft is the third in a series of four patient-focused drug development guidance documents that the FDA had to create as part of the 21st Century Cures Act, and they describe how stakeholders (patients, caregivers, researchers, medical product developers and others) can collect and submit patient experience data and other relevant information for medical product development and regulatory decision-making.

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Rob Etherington, Clene CEO

Star­tup's gold nanocrys­tal ALS drug flops a PhII tri­al, a re­minder of the dis­ease's ob­sta­cles de­spite Amy­lyx OK

Despite the FDA approving an ALS drug for the first time in five years last week, the disease continues to fluster researchers, and another biotech is feeling the pain of a mid-stage failure.

Clene Nanomedicine reported early Monday that its ALS program, which uses gold nanocrystals to try to catalyze intracellular reactions, did not achieve its Phase II primary or secondary endpoints. And in a press release, the company noted for the first time that it’s speaking with “potential strategic partners” about the program — language that typically indicates a biotech is preparing to sell off an asset.

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Albert Bourla, Pfizer CEO (Gian Ehrenzeller/Keystone via AP)

Can a smart­phone app de­tect Covid? Pfiz­er throws down $116M to find out

What can a cough say about a patient’s illness? Quite a bit, according to ResApp Health — and Pfizer’s listening.

The pharma giant is shelling out about $116 million ($179 million AUD) to scoop up the University of Queensland spinout and its smartphone technology that promises to diagnose Covid and other respiratory illnesses based on cough and breathing sounds, the university announced last week.

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An­oth­er warn­ing let­ter for Lupin as FDA iden­ti­fies de­fi­cien­cies at In­dia-based site

With few new details of what needs fixing, Lupin disclosed last week that the FDA recently sent a warning letter to its Tarapur, India-based site.

After an inspection from March 22 to April 4, Lupin disclosed in an April stock filing that it received a Form 483 with four observations, but it didn’t offer any details on the observations.

Similar to comments made in April, the company said last week it does not believe the FDA slap will disrupt its drug supplies or the existing revenues from operations of this facility.

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Silviu Itescu, Mesoblast CEO

Mesoblast sends in im­proved po­ten­cy as­say, look­ing to re­sub­mit to FDA on acute graft-ver­sus-host dis­ease drug

In 2020, the FDA rejected Mesoblast’s remestemcel-L, or Ryoncil, its lead candidate for pediatric acute graft-versus-host disease (aGVHD) that didn’t respond to steroids. The FDA raised a number of concerns, first objecting to Mesoblast’s single arm, open-label trial, though regulators struggled to describe how a randomized trial would work, since pediatricians and parents were reluctant to put children with aGVHD in a placebo arm.

Tim Whitten, Taiho Oncology CEO

FDA green­lights Ot­su­ka sub­sidiary's bile duct can­cer drug

Otsuka subsidiary Taiho Oncology nabbed an accelerated approval on Friday for Lytgobi (futibatinib), its new kinase inhibitor to treat adults with a type of previously treated bile duct cancer, known as metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.

The accelerated approval (meaning a confirmatory trial is necessary to show clinical benefit) follows a shortened six-month review, thanks to the FDA’s Real-Time Oncology Review program.