Up­dat­ed: FDA gives Cel­lec­tis all clear af­ter pa­tient death halt­ed off-the-shelf CAR-T tri­al

Four months af­ter a pa­tient death forced Cel­lec­tis to halt one of their off-the-shelf CAR-T tri­als, the FDA has giv­en them the OK to start dos­ing pa­tients again.

The Paris-based biotech said they changed the study’s pro­to­col to ac­com­mo­date the agency’s con­cerns, al­though they will still have to work with in­ves­ti­ga­tors to ob­tain lo­cal ap­proval to restart the tri­al and start re­cruit­ing pa­tients again. Pri­or its halt, the Phase I had sites in New York, New Jer­sey and Texas.

Cel­lec­tis did not dis­close what the changes were, but af­ter the ini­tial hold, an­a­lysts sug­gest­ed the com­pa­ny might mon­i­tor pa­tient cy­tokine lev­els more close­ly, swap out of one of the chemother­a­py drugs used or pre­vent pa­tients who have pre­vi­ous­ly re­ceived an ex­per­i­men­tal mul­ti­ple myelo­ma CAR-T from en­rolling.

The com­pa­ny’s stock {CLLS} rose 5.6% on the news, from $19.70 to $20.80.

Though part­nered with the new up­starts such as Arie Bellde­grun’s Al­lo­gene, Cel­lec­tis, a 21-year-old com­pa­ny, has been work­ing on off-the-shelf ver­sions to the first CAR-Ts since be­fore those CAR-Ts were ap­proved.

Car­rie Brown­stein

One of three dif­fer­ent so­lo projects now in the clin­ic, the halt­ed study, MELANI-01, is test­ing a cell ther­a­py for mul­ti­ple myelo­ma. If ef­fec­tive, it could serve as a po­ten­tial­ly eas­i­er way to man­u­fac­ture and ad­min­is­ter an al­ter­na­tive to the mul­ti­ple myelo­ma CAR-Ts now near­ing ap­proval from J&J and Leg­end Biotech and from blue­bird bio and Bris­tol My­ers Squibb.

When they an­nounced the hold, Cel­lec­tis CMO Car­rie Brown­stein said that the com­pa­ny had al­ready in­de­pen­dent­ly de­cid­ed to move for­ward with dose lev­el 1 in the study. The pa­tient who died had been the first to re­ceive dose lev­el 2, an in­fu­sion of 3 mil­lion cells per kilo­gram. They de­vel­oped cy­tokine re­lease syn­drome, the hall­mark side ef­fect of CAR-T ther­a­py, and died of car­diac ar­rest 25 days lat­er.

The dose 1 lev­el in­volves 1 mil­lion cells per kilo­gram.

The FDA has been on high alert for safe­ty is­sues in cell ther­a­py tri­als, and this wasn’t the first time they’ve paused a Cel­lec­tis study. Back in 2017, an­oth­er pa­tient death paused de­vel­op­ment of UCART123.

Af­ter some pro­to­col ad­just­ments, the ther­a­py was al­lowed to go back in­to pa­tients. It is now in a Phase I for acute myeloid leukemia.

Im­ple­ment­ing re­silience in the clin­i­cal tri­al sup­ply chain

Since January 2020, the clinical trials ecosystem has quickly evolved to manage roadblocks impeding clinical trial integrity, and patient care and safety amid a global pandemic. Closed borders, reduced air traffic and delayed or canceled flights disrupted global distribution, revealing how flexible logistics and supply chains can secure the timely delivery of clinical drug products and therapies to sites and patients.

The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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The flu virus (CDC)

Roche tacks on an­oth­er Xofluza in­di­ca­tion as flu sea­son meets pan­dem­ic

Xofluza was heralded as the first new flu drug in 20 years when it got the FDA OK back in 2018. But even so, Roche saw tough competition from cheaper Tamiflu generics that appeared to be nearly as — if not just as — effective.

Now, the pharma says the drug also can be used to prevent influenza after exposure, snagging a new approval and adding to Xofluza’s appeal as flu season meets the pandemic.

In fi­nal days at Mer­ck, Roger Perl­mut­ter bets big on a lit­tle-known Covid-19 treat­ment

Roger Perlmutter is spending his last days at Merck, well, spending.

Two weeks after snapping up the antibody-drug conjugate biotech VelosBio for $2.75 billion, Merck announced today that it had purchased OncoImmune and its experimental Covid-19 drug for $425 million. The drug, known as CD24Fc, appeared to reduce the risk of respiratory failure or death in severe Covid-19 patients by 50% in a 203-person Phase III trial, OncoImmune said in September.

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Pascal Soriot (AP Images)

UP­DAT­ED: As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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A poll sug­gests vac­cine da­ta boost­ed Pfiz­er's pub­lic im­age, but oth­er da­ta point to long road ahead

For much of the pharmaceutical industry, the pandemic presented an opportunity: to prove their value to the world and turn public opinion around on a business much of the country had come to disdain.

That theory — that helping pull the country from a pandemic could neutralize years of anger over high drug prices — was put to its biggest test this month, as three different drugmakers announced data from their Covid-19 vaccines, offering the first major evidence that industry-built inoculations could turn the tide of the outbreak in the US.

Covid-19 roundup: Rus­sia prices vac­cine 't­wo or more times cheap­er' than mR­NA shots; Sino­vac PhI­II da­ta ex­pect­ed in ear­ly De­cem­ber

The world can now purchase its first registered vaccine — at less than $10 per dose.

RDIF, the Russian sovereign wealth fund and an avid backer of Sputnik V, said the vaccine will be available internationally starting from March 2021. A two-dose regimen of the adenovirus-based vaccine, which it has said is more than 90% effective, will cost less than $20.

And they are not shy about inserting themselves right into a rivalry with Western frontrunners, namely Pfizer/BioNTech and Moderna.

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Leonard Schleifer, Regeneron CEO (Andrew Harnik/AP)

Trail­ing Eli Lil­ly by 12 days, Re­gen­eron gets the FDA OK for their Covid-19 an­ti­body cock­tail

A month and a half after becoming the experimental treatment of choice for a newly diagnosed president, Regeneron’s antibody cocktail has received emergency use authorization from the FDA. It will be used to treat non-hospitalized Covid-19 patients who are at high-risk of progressing.

Although the Rgeneron drug is not the first antibody treatment authorized by the FDA, the news comes as a significant milestone for a company and a treatment scientists have watched closely since the outbreak began.