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.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Who’s spend­ing and who’s cut­ting from Big Phar­ma’s $127B R&D bud­get? Here are the top 15 play­ers

A couple of the Big 15 biopharma companies in R&D hit the gas on research spending last year. Merck and Sanofi still have lots to prove in the pipeline, and they’re willing to gamble large sums to make a better future for themselves.

Doing nothing would be infinitely worse.

But collectively, the top players rang up a modest 2.4% increase in spending in 2022, which didn’t cover inflationary pressures. And that set the tone for an extraordinarily cautious year for the industry — even as it laid out about $127 billion to advance new drugs or up the ante on approved therapies.

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Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

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Sally Susman, Pfizer EVP and chief corporate affairs officer

Q&A: Pfiz­er cor­po­rate com­mu­ni­ca­tions chief Sal­ly Sus­man dis­cuss­es book craft­ed in pan­dem­ic and per­son­al lessons

From the political arena to the finance and beauty industries to pharmaceuticals, Pfizer’s Sally Susman has broken barriers, stereotypes and conventions. And now the chief communicator is “Breaking Through,” the title of her first book about effective and innovative communications launching today. The full official title is “Breaking Through: Communicating to Open Minds, Move Hearts, and Change the World.”

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Gun­ning for 2023 ap­proval, GSK de­tails PhI­II da­ta for Jem­per­li in front­line en­dome­tri­al can­cer

GSK has a new slate of data to offer on its PD-1 inhibitor, Jemperli — data that the pharma giant hopes will cement one of the four drug approvals it’s expecting this year.

While Jemperli (dostarlimab) is already approved for a subset of patients with second-line endometrial cancer, GSK set out in the Phase III RUBY trial to test it as an earlier line of treatment while also enrolling a broader group of patients. In an interim analysis, Jemperli was shown to extend progression-free survival for both the subset and the overall trial population when added to chemotherapy.

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Es­pe­ri­on sues Dai­ichi Sankyo, de­mand­ing pay­ment of $300M mile­stone for car­dio drug

Esperion is suing its business partner Daiichi Sankyo, saying the Japanese drugmaker is improperly refusing to pay a $300 million milestone that the biotech company will be owed after reporting positive data from a large trial of its cardiovascular drug Nexletol.

The 2019 deal between the companies had Daiichi Sankyo pay $150 million upfront plus another $150 million after the first sales of the drug. But another major payout was tied to an outcomes study reported this month, known as CLEAR. Esperion, in its suit against Daiichi, argues that the drug’s more than 20% reduction of heart attack risk is enough to trigger a $300 million payout from Daiichi once it’s added to the drug’s label.

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Robert Califf, FDA commissioner (Photo by Drew Angerer/Getty Images)

House com­mit­tee to in­ves­ti­gate FDA's re­sponse to on­go­ing drug short­ages

Republican leaders of the House Committee on Energy & Commerce sent a five-page letter yesterday announcing an investigation into the ongoing drug shortages that have rankled the US during the pandemic and the FDA’s response to it.

The letter, signed by Chair Cathy McMorris Rodgers (R-WA), explains how shortages have become more common over the past decade, while pointing to a report from the National Academies of Science, Engineering and Medicine finding that drug shortages have been “on the rise” over the past several decades and are lasting longer, with new drug shortages in the US seeing a 30% increase from 2021 to 2022.

Eli Lil­ly to in­crease in­vest­ment to $1B in­to new Irish man­u­fac­tur­ing fa­cil­i­ty — re­port

The US pharma giant Eli Lilly will be increasing its financial commitment to a manufacturing site in Ireland.

According to a release from Ireland’s Industrial Development Agency (IDA) on Monday, Lilly will be investing another $500 million in its manufacturing facility in Limerick, Ireland — bringing the total investment into the facility to approximately $1 billion.

In January of last year, Lilly announced it was placing a $446 million investment into the site to expand active pharmaceutical ingredient and monoclonal antibody production.

Uğur Şahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

BioN­Tech read­ies for plunge in Covid sales, will boost mR­NA and on­col­o­gy pipelines

BioNTech is estimating €5 billion (nearly $5.4 billion) in Covid-19 vaccine sales this year, a marked drop from €17.1 billion ($18.5 billion) in 2022 — and way off analysts’ expectations of around €8 billion ($8.6 billion).

In BioNTech’s year-end earnings call on Monday, it reported a total of €17.3 billion ($18.7 billion) in 2022 revenue, almost all from vaccine sales, which include those via its Pfizer deal and direct sales.

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