Pfiz­er has run 41 tri­als over 15 years for tanezum­ab. As ad­comm nears, the FDA re­mains unim­pressed — and more than a lit­tle wor­ried

Ahead of an ad­vi­so­ry com­mit­tee meet­ing lat­er this week, the FDA on Mon­day re­leased its in-depth re­view of Pfiz­er and Eli Lil­ly’s an­ti-NGF os­teoarthri­tis drug tanezum­ab, con­clud­ing that it “pro­vides sub­stan­tial ev­i­dence of ef­fec­tive­ness” but al­so rais­ing con­cerns that the pro­posed risk eval­u­a­tion and mit­i­ga­tion strat­e­gy (REMS) may not be enough to lessen its sig­nif­i­cant safe­ty risks.

The safe­ty ques­tions at hand deal with re­ports of un­usu­al and un­ex­pect­ed joint-re­lat­ed ad­verse events in tanezum­ab-treat­ed pa­tients with os­teoarthri­tis, FDA ex­plained, not­ing, “The re­view team has con­cerns that the Ap­pli­cant’s pro­posed REMS is not suf­fi­cient to mit­i­gate the risk of RPOA [Rapid­ly Pro­gress­ing Os­teoarthri­tis] and would not en­sure that the ben­e­fits of tanezum­ab out­weigh the risks of RPOA.”

The FDA on Wednes­day and Thurs­day (for a half day) will con­vene a joint meet­ing of its Arthri­tis Ad­vi­so­ry Com­mit­tee and Drug Safe­ty and Risk Man­age­ment Ad­vi­so­ry Com­mit­tee to re­view the mon­o­clon­al an­ti­body. The com­mit­tees will vote on one ques­tion at the end of the meet­ings, “Will the REMS pro­posed by the Ap­pli­cant en­sure that the ben­e­fits of tanezum­ab out­weigh its risks?”

Al­though FDA said tanezum­ab proved to be ef­fec­tive, its ef­fect size “is mod­est, and there is no con­vinc­ing ev­i­dence of a su­pe­ri­or ef­fi­ca­cy of tanezum­ab over NSAIDs.”

And the agency said there is “no clear ev­i­dence to sup­port that re­quir­ing and im­ple­ment­ing the pro­posed el­e­ments” of the REMS will have an im­pact on pre­vent­ing or the pro­gres­sion of the joint-re­lat­ed risks.

“Most of the joint safe­ty events were de­tect­ed to­wards the end of the treat­ment and dur­ing the fol­low-up pe­ri­od af­ter the ces­sa­tion of treat­ment. As there is no ev­i­dence that the risk plateaus, it is un­known whether the rates and risk will ac­cel­er­ate or plateau with con­tin­ued dos­ing past one year,” FDA said in its brief­ing doc­u­ment.

In ad­di­tion, the agency said tanezum­ab is as­so­ci­at­ed with an el­e­vat­ed risk of re­quir­ing a to­tal joint re­place­ment, as ob­served in two of the three post-2015 clin­i­cal stud­ies, with ev­i­dence of dose re­sponse. There is al­so ev­i­dence that the risk for de­vel­op­ing joint de­struc­tion is 2- to 3-fold high­er if NSAIDs and tanezum­ab are used to­geth­er, FDA said.

“Fur­ther­more, even if the mit­i­ga­tion strate­gies em­ployed in the clin­i­cal tri­al demon­strat­ed ef­fec­tive­ness, it is un­clear that those strate­gies could be repli­cat­ed in clin­i­cal prac­tice,” FDA said.

The ad­comm meet­ings lat­er this week will cap a long and ques­tion-filled de­vel­op­ment pro­gram for tanezum­ab, which has been in de­vel­op­ment for more than 15 years, across 41 clin­i­cal stud­ies and at least 43 for­mal meet­ings with the FDA.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Marianne De Backer (L) and Jeff Hatfield

Bay­er nabs star biotech Vi­vid­ion with a $2B buy­out and an ‘arms-length’ pact, pulling a part­ner out of the IPO con­ga line

Vividion is canceling that IPO it filed. Instead of following the industry-wide migration to Nasdaq, the biotech that has captured considerable attention for its still-preclinical work finding cryptic pockets to bind to on proteins is going to work for Bayer now.

The pharma giant is putting out word today that it has bought out Vividion for $1.5 billion in cash and another half-billion dollars in milestones.

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Tadataka Yamada (Photographer: Kiyoshi Ota/Bloomberg via Getty Images)

Sci­ence pi­o­neer, phar­ma re­search chief, glob­al health ad­vo­cate and biotech en­tre­pre­neur Tadata­ka ‘Tachi’ Ya­ma­da has died

Tadataka Yamada, a towering physician-scientist who made his name in academia before transforming drug development at GlaxoSmithKline and developing vaccines for malaria and meningitis at the Gates Foundation, died unexpectedly of natural causes at his home in Seattle Wednesday morning.

He was 76. Frazier Healthcare Partners’ David Socks confirmed his death.

Known widely by the mononym “Tachi,” Yamada had a globetrotting career and arrived in industry relatively late in life. A 2004 Independent article noted GSK had asked Yamada to stay on beyond his approaching 60th birthday, the company’s usual retirement age. Yamada would continue working for the next 17 years, steering the Gates Foundation’s global health division for 6 years, funding Jim Wilson’s gene therapy work when few would touch it, launching Takeda Vaccines and co-founding a series of high-profile biotechs.

UK re-in­ves­ti­gates Pfiz­er's eye-pop­ping price goug­ing on an epilep­sy drug

When a drugmaker raises the price of a drug in the US by more than 2,000% overnight, and without any particular reason for that increase, nothing typically happens to the company. No fines, no court orders, just business as usual.

Martin Shkreli’s decades-old anti-parasitic drug Daraprim was the perfect example — massive price spike on an old drug, lots of media attention, public outcry, Congressional committees dragging his former company through multiple hearings, and at the end of it? Nothing happened to the price or the company (until generic competition came).

Thomas Lingelbach, Valneva CEO

A small vac­cine de­vel­op­er fa­vored by the UK gov­ern­ment in Covid-19 touts a PhI­II first in chikun­gun­ya

Before Valneva garnered the favor of the UK government as a potential supplier of Covid-19 vaccines, the French biotech prided itself on being the first company to bring a chikungunya vaccine into Phase III.

It now has positive pivotal results to back up the breakthrough therapy designation the FDA granted just weeks ago.

There are currently no approved jabs to prevent chikungunya virus infection despite decades of R&D efforts, a fact that underscores just how arduous traditional vaccine development can be, particularly for neglected tropical disease. In a absence of a major commercial market, the US government and NGOs such as CEPI have deployed various grants and incentives to spur on a small crew of academics and industry players, with Merck, via its acquisition of Themis, claiming a spot in that race.

Josh Hoffman, outgoing Zymergen CEO (Zymergen)

UP­DAT­ED: Syn­bio uni­corn Zymer­gen jet­ti­sons found­ing CEO, cuts guid­ance as cus­tomers re­port lead prod­uct does­n't work

Zymergen, just months off a $500 million IPO that put the synthetic bio firm in rarified air, has now ejected its founding CEO and downgraded its revenue forecasts after customers reported its lead film product doesn’t work as advertised, the company said Tuesday afternoon.

CEO Josh Hoffman will leave his role and sacrifice his board seat immediately in favor of Jay Flatley, the former CEO of Illumina who will take the lead role on an interim basis as the company conducts a search for its next leader.

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Bio­gen, Ei­sai are push­ing for an­oth­er ac­cel­er­at­ed Alzheimer's OK — this time for BAN2401

Now that the door at the FDA has been opened wide for Alzheimer’s drugs that can demonstrate a reduction in amyloid, Biogen and its partners at Eisai are pushing for a quick OK on the next drug to follow in the controversial path of aducanumab.

In a presentation to analysts, Eisai neurology chief Ivan Cheung outlined some bullish expectations for their newly-approved treatment and set the stage for what he believes will be a fast follow for BAN2401 (lecanemab) — after a dry spell in new drug development that’s lasted close to 20 years.

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Zymergen co-founders Zach Serber, Josh Hoffman, and Jed Dean (Zymergen via website)

Zymer­gen's sud­den im­plo­sion shocked biotech. A lin­ger­ing loan could make things even worse

As former synbio unicorn Zymergen picks up the pieces from its spectacular implosion Tuesday, an outstanding loan from Perceptive Advisors — the only blue-chip biotech crossover investor to touch Zymergen’s fundraising efforts — could make the situation worse, according to public documents.

In December 2019, more than a year before Zymergen filed for what would eventually become a $500 million IPO, the “biofacturing” firm signed a $100 million credit facility with Perceptive to help supplement the nearly $700 million the company had raised across four VC rounds.

Janet Woodcock (Bill Clark/CQ Roll Call via AP Images)

HHS ex­tends Aduhelm in­ves­ti­ga­tion in­to the ac­cel­er­at­ed ap­proval path­way, wad­ing in­to a brew­ing con­tro­ver­sy

The government investigation into how the FDA approved Aduhelm appears to point well beyond the agency’s ties with Biogen in the leadup to its approval of their controversial Alzheimer’s drug Aduhelm.

The HHS Office of Inspector General posted a notice Wednesday that officials will review the accelerated approval pathway, the regulatory mechanism the agency used to approve the drug in the face of conflicting data over whether it could actually slow Alzheimer’s patients’ mental decline. Now the Aduhelm OK is just one branch of an investigation called for last month by acting FDA commissioner Janet Woodcock.

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