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.

Charles Baum, Mirati CEO

Mi­rati plots a march to the FDA for its KRAS G12C drug, breath­ing down Am­gen’s neck with bet­ter da­ta

Mirati Therapeutics $MRTX took another closely-watched step toward a now clearly defined goal to file for an approval for its KRAS G12C cancer drug adagrasib (MRTX849), scoring a higher response rate than the last readout from the class-leading rival at Amgen but still leaving open a raft of important questions about its future.

Following a snapshot of the first handful of responses, where the drug scored a tumor response in 3 of 5 patients with non-small cell lung cancer, the response rate has now slid to 45% among a pooled group of 51 early-stage and Phase II patients, 43% — 6 of 14 — when looking solely at the Phase I/Ib. Those 14 patients had a median treatment duration of 8.2 months, with half still on therapy and 5 of 6 responders still in response.

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In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Covid-19 roundup: An mR­NA play­er gets a boost out of the lat­est round of an­i­mal da­ta; Phase­Bio pulls the plug on treat­ment tri­al

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.

Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

UP­DAT­ED: FDA anoints Gilead­'s remde­sivir as the Covid-19 treat­ment win­ner, hand­ing down full ap­proval — de­spite some deep skep­ti­cism

Seven months into the Covid-19 pandemic, the race to develop a treatment for the disease that’s proved to be the biggest health crisis in a century has an officially designated winner: Gilead. And they’re picking up the prize — worth billions in peak sales — despite a major study that concluded the drug was no help in reducing the number of people who die from the virus.

The FDA handed down a thumbs-up for remdesivir, the company announced Thursday afternoon, as the drug becomes the first fully approved treatment for Covid-19 in the US. Remdesivir, to be marketed as Veklury, will come with a label for treatment in adults and children older than 12 in Covid-19 cases that require hospitalization.

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Stephen Hoge, Moderna president (Moderna)

On morn­ing of FDA Covid-19 ad­comm, Mod­er­na com­pletes PhI­II en­roll­ment, putting them neck-and-neck with Pfiz­er

Weeks away from a potential EUA application, Moderna announced they have completed enrollment in their 30,000-person Phase III Covid-19 vaccine trial, with over a third of volunteers non-white and a quarter over the age of 65.

The announcement caps what has been the most closely-watched recruitment race in the history of drug development, as Pfizer and Moderna rushed to get enough volunteers to prove whether or not experimental vaccines could actually protect people from contracting Covid-19. Pfizer reached that mark on Sept. 15. Moderna said around the same time that they would slow down enrollment to ensure they enrolled enough participants from minority and at-risk groups.