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.

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

The notorious drug testing company Valisure, which has made a name for itself by forcing FDA’s hand with some of its safety-related uncoverings, received a letter this week after the FDA uncovered violations at its Connecticut-based testing lab in 2021.

The letter, which was sent on Dec. 5, stated that the FDA is “concerned” that Valisure was not aware of  drug supply chain security requirements.

Republicans have taken a stand against the pandemic era habit of lax work-from-home schedules. Now that they’ve wrestled control of the House majority, the FDA’s leadership is playing ball, sending many of the agency’s more than 18,000 employees back to their desks early next year.

Whether this exodus back to White Oak in Silver Spring, MD (many staff will still be allowed to work from home for multiple days per week) will mean more defections to industry and elsewhere remains to be seen.

The generics manufacturer Lupin has been given another Form 483 from the FDA this year.

US regulators inspected Lupin’s pharmaceutical manufacturing site in the town of Mandideep, India from Nov. 14 through Nov. 23, with the 14-page report marking 16 observations.

The inspection report stated that the site did not have the appropriate controls over its computer systems to ensure that changes in “master production” or records are only done by authorized personnel, along with written procedures not being established to conduct annual reviews of records associated with drug batches.

The FDA is struggling to remove drugs from the marketplace that don’t show effectiveness in late stage trials, new JAMA analyses found, thanks to the persistent tension between speed and confidence in early clinical data.

Congress, regulated industry and patients have urged the FDA to shorten the amount of time that the market has to wait for drugs to become available that may help severe and prevalent diseases – and the FDA has listened, offering up a quick accelerated approval pathway that’s frequently used by new cancer drugs.