FDA seeks with­draw­al of heart­burn drugs due to new car­cino­gen con­cerns

The FDA on Wednes­day re­quest­ed that all man­u­fac­tur­ers of drugs con­tain­ing ran­i­ti­dine (com­mon­ly known as Zan­tac and used for heart­burn) re­move all pre­scrip­tion and over-the-counter (OTC) ver­sions from the mar­ket be­cause the car­cino­gen N-Ni­troso­di­methy­lamine (ND­MA) has now been found to in­crease sig­nif­i­cant­ly in sam­ples stored at high­er tem­per­a­tures.

The an­nounce­ment is the most se­ri­ous in a chain of FDA safe­ty ad­vi­sories re­lat­ed to ND­MA in ran­i­ti­dine med­i­cines fol­low­ing a se­ries of re­calls of Zan­tac and oth­er ran­i­ti­dine drugs, and as the agency said last No­vem­ber that the ND­MA lev­els in such drugs “are sim­i­lar to the lev­els you would ex­pect to be ex­posed to if you ate com­mon foods like grilled or smoked meats.”

Now, new FDA test­ing and eval­u­a­tion prompt­ed by in­for­ma­tion from third-par­ty lab­o­ra­to­ries “con­firmed that ND­MA lev­els in­crease in ran­i­ti­dine even un­der nor­mal stor­age con­di­tions, and ND­MA has been found to in­crease sig­nif­i­cant­ly in sam­ples stored at high­er tem­per­a­tures, in­clud­ing tem­per­a­tures the prod­uct may be ex­posed to dur­ing dis­tri­b­u­tion and han­dling by con­sumers,” FDA said.

“The test­ing al­so showed that the old­er a ran­i­ti­dine prod­uct is, or the longer the length of time since it was man­u­fac­tured, the greater the lev­el of ND­MA. These con­di­tions may raise the lev­el of ND­MA in the ran­i­ti­dine prod­uct above the ac­cept­able dai­ly in­take lim­it,” the agency added.

Janet Wood­cock

FDA al­so pre­vi­ous­ly told com­pa­nies to vol­un­tar­i­ly with­draw ran­i­ti­dine and niza­ti­dine prod­ucts that do not meet the agency’s ND­MA thresh­old (96 nanograms per day or 0.32 ppm).

But now FDA is is­su­ing this im­me­di­ate mar­ket with­draw­al re­quest for all man­u­fac­tur­ers, which means ran­i­ti­dine prod­ucts will not be avail­able for new or ex­ist­ing pre­scrip­tions or OTC use in the US.

“Ran­i­ti­dine prod­ucts will stay off the mar­ket un­less a man­u­fac­tur­er can show that their prod­uct is sta­ble while stored and does not gen­er­ate ex­cess ND­MA,” CDER Di­rec­tor Janet Wood­cock said on Twit­ter.

As far as oth­er heart­burn med­i­cines, FDA says that its test­ing has not found ND­MA in famo­ti­dine (Pep­cid), cime­ti­dine (Taga­met), es­omepra­zole (Nex­i­um), lan­so­pra­zole (Pre­vacid) or omepra­zole (Prilosec).

FDA and the Eu­ro­pean Med­i­cines Agency be­gan in­ves­ti­gat­ing the pres­ence of ND­MA in ran­i­ti­dine med­i­cines last Sep­tem­ber.

FDA Re­quest

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Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; 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.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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