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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data is messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data is exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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Boost­er bo­nan­za: FDA en­dors­es 'mix-and-match' scheme, and Mod­er­na and J&J too

The FDA late Wednesday signed off on authorizing the use of heterologous — or what FDA calls a “mix and match” of a primary vaccine series and different booster doses — for all currently available Covid-19 vaccines, in addition to separately authorizing Moderna and J&J boosters.

On the mix-and-match approach, which FDA officials insisted isn’t too confusing in a press conference, the agency offered the example of an 18-year-old who received the J&J shot at least two months ago and may now receive a single booster of the J&J, a half dose of the Moderna, or the Pfizer-BioNTech booster.

Leen Kawas (L) has resigned as CEO of Athira and will be replaced by COO Mark Litton

Ex­clu­sive: Athi­ra CEO Leen Kawas re­signs af­ter in­ves­ti­ga­tion finds she ma­nip­u­lat­ed da­ta

Leen Kawas, CEO and founder of the Alzheimer’s upstart Athira Pharma, has resigned after an internal investigation found she altered images in her doctoral thesis and four other papers that were foundational to establishing the company.

Mark Litton, the company’s COO since June 2019 and a longtime biotech executive, has been named full-time CEO. Kawas, meanwhile, will no longer have ties to the company except for owning a few hundred thousand shares.

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Man­u­fac­tur­ing woes for No­vavax’s Covid jab bad­ly dis­rupt plans for roll­out to the poor — re­port

Production problems at a Novavax facility in Maryland have led to delays in the Covax vaccine sharing program. Now, a shortage of 1 billion doses is expected, as the supplier tries to navigate producing a shot up to regulators’ standards, Politico reported Tuesday.

The company has run into trouble with the purity of the vaccine. Novavax has had trouble proving it can produce a shot consistently up to standards, and it has caused significant delays in the rollout to low- and middle-income countries. This follows several delays at Novavax that has put the executive crew on the defensive.

Bill Gates at the Global Investment Summit in London, Oct. 19, 2021 (Leon Neal/Pool via AP Images)

Gates Foun­da­tion pledges $120M to ramp up gener­ic sup­ply of Mer­ck­'s Covid-19 pill while ac­tivists blast Pfiz­er's dis­pro­por­tion­ate pow­er

Merck’s molnupiravir may not be officially authorized anywhere in the world yet, but who will get access to it has shaped up to be a huge issue. The Bill & Melinda Gates Foundation is now stepping up to ensure lower-income countries won’t be left behind — and calling on others to follow its lead.

The oral antiviral pill, which was shown to dramatically cut the risk of severe Covid-19 disease and death in a Phase III study, is the latest rallying symbol in the battle against not just the coronavirus but the inequality it’s exposed.

Sen. Richard Durbin (D-IL, foreground) and Sen. Richard Blumenthal (D-CT) (Patrick Semansky/AP Images)

Sen­a­tors back FDA's plan to re­quire manda­to­ry pre­scriber ed­u­ca­tion for opi­oids

Three Senate Democrats are backing an FDA plan to require mandatory prescriber education for opioids as overdose deaths have risen sharply over the past decade, with almost 97,000 American opioid-related overdose deaths in the past year alone.

While acknowledging a decline in overall opioid analgesic dispensing in recent years, the FDA said it’s reconsidering the need for mandatory prescriber training through a REMS given the current situation with overdoses, and is seeking input on the aspects of the opioid crisis that mandatory training could potentially mitigate.