Genentech’s tocilizumab shortage due to Covid-19 now hits CAR-T recipients, with FDA offering alternatives to help

Soon af­ter San Fran­cis­co-based Genen­tech won an EUA for tocilizum­ab as a treat­ment for hos­pi­tal­ized Covid pa­tients last sum­mer, the com­pa­ny an­nounced a short­age of the drug while point­ing to the emer­gence of the Delta vari­ant and the slow­ing of vac­ci­na­tion rates across the US.

‘This new wave of the pan­dem­ic has led to Genen­tech ex­pe­ri­enc­ing an un­prece­dent­ed de­mand for Actem­ra IV– well-over 400% of pre-COVID lev­els over the last two weeks alone and it con­tin­ues to in­crease,’ the com­pa­ny said in Au­gust.

More re­cent­ly, the short­age is caus­ing is­sues for oth­ers who might need tocilizum­ab fol­low­ing the in­fu­sion of CAR-T cell im­munother­a­pies as can­cer treat­ments, due to the po­ten­tial for se­vere or even life-threat­en­ing cy­tokine re­lease syn­drome.

All CAR-Ts are sub­ject to risk eval­u­a­tion and mit­i­ga­tion strate­gies (REMS) OKed by the FDA, which in this case re­quire that pri­or to CAR-T in­fu­sions, a min­i­mum of two dos­es of tocilizum­ab are avail­able on-site for each pa­tient and are ready for im­me­di­ate ad­min­is­tra­tion (with­in 2 hours) due to the po­ten­tial for CRS.

The world­wide short­age of tocilizum­ab means the FDA has to get flex­i­ble with its re­quire­ment that two dos­es be on site, and the agency is­sued new guid­ance on Fri­day ex­plain­ing how.

For CAR T cell im­munother­a­pies sub­ject to these REMS, the FDA says it does not in­tend to ob­ject if health care providers pre­scribe, dis­pense, or ad­min­is­ter these bi­o­log­ics when two dos­es of tocilizum­ab are not avail­able, pro­vid­ed that all of the fol­low­ing cir­cum­stances are ac­count­ed for:

Be­fore in­fu­sion of the CAR-T im­munother­a­py to a pa­tient, one dose of tocilizum­ab is avail­able on-site for each pa­tient for im­me­di­ate ad­min­is­tra­tion (with­in 2 hours), and there is ac­cess to an ad­di­tion­al dose of tocilizum­ab with­in 8 hours af­ter each pre­vi­ous dose, if need­ed.

Health care providers use their best med­ical judg­ment in weigh­ing the ben­e­fits and risks of treat­ment with the CAR T cells in the con­text of the short­age. ‘There are lim­it­ed da­ta to sup­port the use of al­ter­na­tive agents di­rect­ed against in­ter­leukin (IL)-6 or oth­er cy­tokines for CRS man­age­ment in gen­er­al, and in par­tic­u­lar, as first-line ther­a­py,’ FDA notes.

Health care providers com­mu­ni­cate with their pa­tients re­gard­ing their de­ci­sion-mak­ing, in­clud­ing the risks and ben­e­fits of treat­ment with CAR T cell im­munother­a­py in the con­text of the tocilizum­ab short­age, and the po­ten­tial chal­lenges in the treat­ment of CRS and po­ten­tial use of al­ter­na­tive CRS man­age­ment ap­proach­es.

Un­der the REMS, cer­ti­fied hos­pi­tals and their as­so­ci­at­ed clin­ics al­so should main­tain ad­e­quate records of pa­tient-lev­el da­ta re­gard­ing the use of CAR T cell im­munother­a­pies and must doc­u­ment and re­port any se­ri­ous ad­verse events sug­ges­tive of CRS or neu­ro­log­i­cal tox­i­c­i­ty, the FDA says.

Genen­tech al­so must main­tain records of cer­ti­fied hos­pi­tals and their as­so­ci­at­ed clin­ics that were not able to com­ply with REMS re­quire­ments and in­stead pro­vide CAR T cell im­munother­a­py in a man­ner con­sis­tent with this pol­i­cy due to the tocilizum­ab short­age.

‘Al­though all REMS re­quire­ments re­main in ef­fect dur­ing this time, FDA does not in­tend to take en­force­ment ac­tion against spon­sors or oth­ers with re­spect to the REMS re­quire­ments re­lat­ing to the ac­cess to tocilizum­ab’ dur­ing this short­age, the agency adds.

Sensor-based technology for clinical trial data collection represents the latest medical paradigm shift. There are more than 700 clinical studies involving wearable devices currently underway in the United States. A study from Intel IT projects their inclusion in clinical trials will surge to 70% by 2025.

Apps, biosensors and patient-centered technologies increase visibility of comprehensive patient data. Pharma leaders anticipate the benefits of wearables to include better data (58%), faster results (33%) and lower trial costs (10%).

When Bristol Myers Squibb celebrated the approval of ozanimod — branded Zeposia — in ulcerative colitis earlier this year, the company touted the first gastrointestinal indication for an S1P receptor modulator.

Now Pfizer wants to give the pharma rival a run for its money.

Pfizer is dropping $6.7 billion to acquire Arena Pharmaceuticals, whose lead drug, etrasimod, targets the sphingosine 1-phosphate receptor.

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Merck’s potential Covid-19 treatment molnupiravir will not be used in France, French regulators said Friday.

The French National Authority of Health cited the potential impact of the Omicron variant, the fact that Regeneron’s mAb cocktail is more effective, and the pill’s own lack of efficacy as reasons for denying early access of the drug to patients experiencing mild to moderate cases of Covid-19. France has already pre-ordered hundreds of thousands of the pills, with the goal of treating 50,000 patients.

Rumors have swirled around a potential buyout of Switzerland’s Vifor Pharma by Australia’s CSL since the start of December, and now the gossip reportedly has some truth to it.

Vifor confirmed to Reuters early Monday that it is in discussions to be acquired by CSL for more than $8.5 billion, sending its shares up more than 15% in overseas trading. The deal is expected to be finalized Tuesday, according to Australian media, with one large investor reportedly willing to pay more than $173 per share — about $60 more than Vifor’s price before the rumors began circulating on Dec. 2.

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Gene therapy biotech Intellia Therapeutics has dosed its first patient with genome editing candidate NTLA-2002, its drug candidate for hereditary angioedema, a rare genetic condition that causes swelling under the skin.

The drug candidate has been under development as a single-dose gene therapy to prevent HAE attacks by inactivating the target gene kallikrein B1 (KLKB1). That would, Intellia hopes, reduce plasma kallikrein activity and thus prevent HAE attacks.

AbbVie’s Migraine Relief-Tok on TikTok

Relaxation apps have nothing on AbbVie migraine med Ubrelvy’s TikTok. Ocean waves and birds chirping offer respite and a quiet scrolling break on the more typically frenetic social media app.

AbbVie calls it Migraine Relief-Tok and in a series of ads feature different calming sounds of nature with the advice: ‘Take a Break. Breathe in, Breathe out.’

The unexpected quiet in what can be an overstimulating experience of music, dancing, pop culture and politics is intentional. AbbVie knows that like many people, the 40 million people who suffer from migraine, are also on social media and TikTok.

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In the face of short attacks, it is not uncommon these days for companies to cry foul and defend themselves against what they call false and misleading statements. But are these short sellers involved in something more nefarious? The Department of Justice is reportedly trying to find out through a sweeping criminal investigation.

Federal investigators are scrutinizing an unknown number of hedge funds and research firms — alongside their trading of at least several dozen shorts — to see if any kind of deception or manipulation was involved, Reuters and Bloomberg reported.

Roberto Bellini, Bellus Health CEO

Do investors want the good news, or the bad news first? Bellus went with the good news, sharing that its chronic cough contender hit the primary endpoint in a Phase IIb trial, lining it up for a Phase III study in the second half of next year where it could pose stiff competition for Merck.

Amidst all the commotion, the Canadian biotech also revealed that the same candidate flunked a proof-of-concept trial in atopic dermatitis, and the company will now steer the program away from pruritic conditions.

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The Senate Finance Committee on Saturday released the latest text of President Joe Biden’s $2 trillion spending package, paid for at least in part with new negotiating power for Medicare and inflation rebates drugmakers will have to pay if their drug prices rise too quickly each year.

But now, generic drugs at risk of shortage and biosimilars have been cut out of the rebates, as their industry lobbying groups had sought. They’d said the inclusion of such rebates and negotiations could increase the likelihood of drug shortages and create barriers to competition.
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