An­oth­er day, an­oth­er AAV-de­liv­ered gene ther­a­py run­ning in­to road­blocks with the FDA.

The agency has placed a clin­i­cal hold on Log­icBio’s AAV-de­liv­ered gene edit­ing ther­a­py LB-001 af­ter two ado­les­cent pa­tients in an ear­ly tri­al for the drug were di­ag­nosed with throm­bot­ic mi­croan­giopa­thy (TMA), a clin­i­cal syn­drome de­fined by the for­ma­tion of tiny clots in blood ves­sels, the com­pa­ny said Wednes­day.

The biotech is try­ing LB-001 in a Phase I/II tri­al dubbed SUN­RISE to treat chil­dren with the rare meta­bol­ic dis­ease methyl­malonic acidemia, which re­sults in pa­tients not be­ing able to break down cer­tain fats and pro­teins.

In that study, two of four pa­tients re­port­ed cas­es of TMA, nei­ther of which proved fa­tal. In the first case, Log­icBio in­sti­tut­ed new safe­ty pro­to­cols in the SUN­RISE tri­al fol­low­ing the pa­tient’s di­ag­no­sis. That case was re­solved as of De­cem­ber 2021.

In the sec­ond case, the pa­tient was di­ag­nosed with TMA in Jan­u­ary of this year and is cur­rent­ly be­ing mon­i­tored.

With now two cas­es re­port­ed, the FDA opt­ed to halt de­vel­op­ment un­til more in­fo on what ex­act­ly caused those side ef­fects is picked out. In the mean­time, Log­icBio has said it’s putting tri­al da­ta up­dates on pause and work­ing with the agency to get the study back up and run­ning.

TMA has been a com­mon stum­bling block be­fore in gene ther­a­py stud­ies, a fact which Log­icBio ad­mit­ted in its re­lease. But it’s still not a wel­come re­sult for the com­pa­ny or its lead drug. LB-001 pur­ports to work by in­sert­ing a cor­rec­tive copy of the methyl­malonyl-CoA mu­tase gene in­to hu­man cells, dri­ving ther­a­peu­tic pro­duc­tion of that en­zyme in the liv­er.

Shares in $LOGC were trad­ing down 34% be­fore the bell Wednes­day.

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 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 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.