Roche says a sec­ond tri­al of Actem­ra re­vives hopes for IL-6. What now?

Roche’s Actem­ra — and the IL-6 drug class by ex­ten­sion — may have a role in the fight against Covid-19 af­ter all.

Da­ta from a new Phase III study showed that adding the drug to stan­dard of care could re­duce hos­pi­tal­ized pa­tients’ like­li­hood of need­ing mech­a­nism ven­ti­la­tion, the Swiss phar­ma gi­ant re­port­ed. Im­por­tant­ly, the ma­jor­i­ty of the 389 en­rolled pa­tients are from mi­nor­i­ty racial and eth­nic groups who are of­ten un­der­rep­re­sent­ed in clin­i­cal tri­als but bear the brunt of the pan­dem­ic.

On the pri­ma­ry end­point, pa­tients with Covid-as­so­ci­at­ed pneu­mo­nia who took Actem­ra were 44% less like­ly to need mech­a­nism ven­ti­la­tion or die down the road, com­pared to the place­bo arm (p-val­ue = 0.0348). The pro­por­tions of pa­tients who did with­in 28 days were 12.2% and 19.3%, re­spec­tive­ly.

Dubbed EM­PACTA, the tri­al used a dif­fer­ent out­come mea­sure from that used in the CO­V­AC­TA study, which al­so in­volved pa­tients with pneu­mo­nia but ap­peared to have re­cruit­ed a more se­vere group, and fo­cused on im­prove­ment in clin­i­cal sta­tus. Actem­ra failed to dif­fer­en­ti­ate it­self from place­bo there, spelling what many as­sumed was an end to the idea of re­pur­pos­ing the rheuma­toid arthri­tis drug to fight the un­con­trolled im­mune re­sponse and lung dam­age that can re­sult from Covid-19.

Levi Gar­raway

Back in Ju­ly, Roche in­ves­ti­ga­tors did high­light one bright spot — a mod­est 0.037 p val­ue for cut­ting the time to dis­charge — which didn’t count for much with the pri­ma­ry end­point flop.

But that da­ta point wasn’t held up in the new num­bers re­leased this morn­ing, as the dif­fer­ence in time to hos­pi­tal dis­charge or “ready for dis­charge” at day 28 was not sta­tis­ti­cal­ly sig­nif­i­cant. Me­di­an days to dis­charge were 6 for Actem­ra and 7.5 for place­bo, with a p-val­ue of 0.2456.

All the oth­er sec­ondary end­points al­so failed to hit sta­tis­ti­cal sig­nif­i­cance, in­clud­ing mor­tal­i­ty and time to clin­i­cal fail­ure.

It’s un­clear how these re­sults would stack up in the eyes of reg­u­la­tors as Roche brings the da­ta to the FDA and oth­er agen­cies around the world. Levi Gar­raway, head of glob­al prod­uct de­vel­op­ment, said that re­duc­ing the need for mech­a­nism ven­ti­la­tion is “an im­por­tant out­come.”

In sep­a­rate stud­ies, Re­gen­eron and Sanofi have con­clud­ed ear­ly on that Kevzara — which works sim­i­lar­ly to Actem­ra, block­ing the cy­tokine IL-6 — was like­ly hav­ing lit­tle ef­fect on most but the most crit­i­cal pa­tients (who are al­ready on ven­ti­la­tors at en­roll­ment). The drug lat­er failed all pri­ma­ry and sec­ondary end­points even in that sub­group, and the part­ners an­nounced they were es­sen­tial­ly pulling a plug on the pro­gram.

Roche is ap­par­ent­ly not ready to give in. There’s one more Phase III study un­der­way test­ing a com­bi­na­tion of Actem­ra and remde­sivir, Gilead’s EUA-blessed an­tivi­ral. Clin­i­cal sta­tus will be the pri­ma­ry end­point for the REM­DAC­TA tri­al, which tar­gets se­vere pa­tients with pneu­mo­nia; sec­ondary end­points in­clude me­chan­i­cal ven­ti­la­tion, mor­tal­i­ty and in­ten­sive care vari­ables.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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In a sup­ply chain short­age workaround, Aus­trali­a's Vic­to­ria state aims to build its own mR­NA fa­cil­i­ty

As countries all around the world have experienced troubles with vaccine shortages, Australia’s Victoria state is developing its own mRNA manufacturing facility in an effort to up its number of vaccinated residents.

Victoria will spend $39 million to set up the facility, which could be the first in the southern hemisphere, Reuters reported. The mRNA technology is used in the Pfizer-BioNTech and Moderna vaccines, and has gotten more attention, as adenovirus-based vaccines from AstraZeneca and J&J have had reports of rare, but similar blood clots in some patients. There have been no reports of major side effects in either Moderna or Pfizer’s jab.

FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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Bay­er plots a ma­jor facelift at Berke­ley cam­pus, un­cork­ing a 30-year, $1.2B plan to dri­ve cell and gene ther­a­pies

Bayer first set roots in Berkeley back in 1974, when it was still operating as Miles Labs. The site has pumped out three hemophilia A treatments for distribution worldwide; but now, as the pharma continues its cell and gene therapy push, it has something bigger in mind.

Bayer is planning a 30-year revamp at the campus, which includes 918,000 square feet in new buildings and double the jobs, according to a report by the Bay Area Council Economic Institute.

LLS backs 5 new can­cer drug projects with up to $50M; Trodelvy con­tin­ues to im­press with more TNBC da­ta

The Leukemia and Lymphoma Society has tapped 5 new early-stage projects to back with up to $10 million each in fresh investments. The 5 biotechs are:

— Caribou, headed by Rachel Haurwitz and co-founded by Jennifer Doudna, is working on next-gen, off-the-shelf CAR-Ts to replace the patient-derived cells now in use.

— The LLS supported NexImmune’s IPO, helping fund its work on nanoparticles that can gin up an immune response directed at cancer cells. The biotech has 2 projects now in Phase I trials.

Steffen Schuster, ITM CEO

Ra­dio­phar­ma re­mains hot as Ger­many's ITM rais­es $109M to ad­vance neu­roen­docrine can­cer pro­gram

The world of radiopharmaceuticals has been heating up over the last few years, and Thursday saw another company focused on the field pull in a new nine-figure raise.

Germany’s ITM, or Isotopen Technologien München, scored a $109 million round of loan financing to push forward its precision oncology pipeline and fund late-stage development for its lead program. As part of the agreement, the loan will convert to shares in the event of future financial or corporate transactions, ITM said.