Need a place­bo con­trol group for your next can­cer drug study? On­ly in cer­tain cir­cum­stances, says FDA

Giv­en the eth­i­cal chal­lenges of us­ing a place­bo in ran­dom­ized con­trolled clin­i­cal tri­als for ther­a­pies to treat hema­to­log­ic ma­lig­nan­cy and on­co­log­ic dis­ease, the FDA rec­om­mends that a spon­sor use a place­bo-con­trolled de­sign on­ly in se­lect cir­cum­stances, ac­cord­ing to new draft guid­ance re­leased Thurs­day.

Such cir­cum­stances in­clude “where sur­veil­lance is stan­dard of care,” or with spe­cif­ic tri­al “de­sign fea­tures (e.g. if the tri­al us­es an add-on de­sign, when the end­point in­tend­ed to sup­port a la­bel­ing claim has a high de­gree of sub­jec­tiv­i­ty, such as pa­tient re­port­ed out­comes).”

And when con­sid­er­ing the use of a place­bo con­trol, the FDA says spon­sors should pro­vide a ra­tio­nale for the tri­al de­sign and a de­tailed de­scrip­tion in the pro­to­col and sta­tis­ti­cal analy­sis plan of the pro­pos­al for blind­ing and un­blind­ing.

“If a spon­sor in­tends to main­tain the treat­ment blind when dis­ease re­curs or pro­gress­es or a sus­pect­ed ad­verse event oc­curs, the in­formed con­sent doc­u­ment should spec­i­fy the risks and po­ten­tial dis­ad­van­tages of this ap­proach, and the pro­to­col should in­clude jus­ti­fi­ca­tion for the po­ten­tial added risk,” the three-page draft says.

The FDA al­so rec­om­mends that spon­sors un­blind a pa­tient “at the time of doc­u­ment­ed dis­ease re­cur­rence or pro­gres­sion to en­sure op­ti­mal pa­tient man­age­ment.”

Con­tin­ued blind­ing at the time of dis­ease pro­gres­sion or oc­cur­rence of se­ri­ous ad­verse events presents ad­di­tion­al chal­lenges, the FDA says.

For ex­am­ple, in a blind­ed im­munother­a­py tri­al, a pa­tient who de­vel­ops ad­verse events on the con­trol arm may re­ceive un­nec­es­sary treat­ments (e.g., im­muno­sup­pres­sive drug prod­ucts in­clud­ing a high dose of glu­co­cor­ti­coids, cy­clophos­phamide, in­ter­leukin-6 an­tag­o­nist, or in­flix­imab) for man­age­ment of ad­verse events in­cor­rect­ly at­trib­uted to the in­ves­ti­ga­tion­al drug prod­uct.

Main­tain­ing the blind af­ter dis­ease pro­gres­sion could al­so af­fect a pa­tient’s sub­se­quent ther­a­py.

The FDA al­so rec­om­mends un­blind­ing the pa­tient and in­ves­ti­ga­tor “when the pa­tient has an ad­verse event sus­pect­ed to be re­lat­ed to the in­ves­ti­ga­tion­al drug prod­uct and for which man­age­ment of the ad­verse event with one or more drug prod­ucts with sub­stan­tial tox­i­c­i­ty or in­va­sive pro­ce­dures is be­ing con­sid­ered. In such cas­es of un­blind­ing, the pa­tient should not be re­moved from the tri­al.”

In terms of the prac­ti­cal and eth­i­cal con­cerns re­lat­ed to us­ing place­bos in some on­col­o­gy tri­als, the FDA notes that in many cas­es, be­cause of the tox­i­c­i­ty of the ac­tive treat­ment, pa­tients and in­ves­ti­ga­tors may know if they are re­ceiv­ing a place­bo treat­ment.


First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion.

In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Adam Koppel and Jeffrey Schwartz, Bain

Bain ex­ecs Adam Kop­pel and Jef­frey Schwartz line up $125M for their first blank check deal as Wall Street con­tin­ues to em­brace biotech

Adam Koppel and Jeffrey Schwartz have jumped into the blank check game, raising $125 million for a stock listing in search of a company.

Their SPAC, BCLS Acquisition Corp, raised $125 million this week, with a line on $25 million more as it scouts for a biotech in search of money and a place on Wall Street.

The two principals at Bain Life Sciences have been on a romp since they set up the Bain operation 4 years ago. Their S-1 spells out a track record of 22 deals totaling $650 million for the life sciences group, which led to 9 IPOs.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

UP­DAT­ED: FDA anoints Gilead­'s remde­sivir as the Covid-19 treat­ment win­ner, hand­ing down full ap­proval — de­spite some deep skep­ti­cism

Seven months into the Covid-19 pandemic, the race to develop a treatment for the disease that’s proved to be the biggest health crisis in a century has an officially designated winner: Gilead. And they’re picking up the prize — worth billions in peak sales — despite a major study that concluded the drug was no help in reducing the number of people who die from the virus.

The FDA handed down a thumbs-up for remdesivir, the company announced Thursday afternoon, as the drug becomes the first fully approved treatment for Covid-19 in the US. Remdesivir, to be marketed as Veklury, will come with a label for treatment in adults and children older than 12 in Covid-19 cases that require hospitalization.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.