Kiniksa whiffs on ef­fi­ca­cy try­ing to re­pur­pose an RA pro­gram for Covid-19, but spins sur­vival 'trend­s' as a pos­i­tive

As the search for more po­ten­tial Covid-19 treat­ments con­tin­ues, Kiniksa Phar­ma­ceu­ti­cals $KN­SA has re­vealed da­ta for a re­pur­posed im­munol­o­gy can­di­date it says are pos­i­tive. But the num­bers paint a much murki­er pic­ture.

The Bermu­da-based biotech whiffed bad­ly on the pri­ma­ry end­point in the small Phase II por­tion of a Phase II/III study for its mavril­i­mum­ab pro­gram, say­ing that af­ter two weeks the pro­por­tion of pa­tients with se­vere Covid-19 who were alive and off sup­ple­men­tal oxy­gen was not sta­tis­ti­cal­ly sig­nif­i­cant com­pared to place­bo. Kiniksa al­so missed the sec­ondary end­point — pro­por­tion of pa­tients alive and with­out res­pi­ra­to­ry fail­ure af­ter four weeks — though it not­ed the da­ta moved in the right di­rec­tion over longer pe­ri­ods.

John Paoli­ni

“The da­ta showed en­cour­ag­ing trends of re­duced mor­tal­i­ty and du­ra­tion of me­chan­i­cal ven­ti­la­tion in pa­tients treat­ed with mavril­i­mum­ab, es­pe­cial­ly when con­sid­er­ing that many pa­tients in this place­bo-con­trolled study had al­ready been treat­ed with remde­sivir and/or cor­ti­cos­teroids,” Kiniksa CMO John Paoli­ni said in a state­ment.

In­vestors were most­ly mut­ed on the news, with Kiniksa shares up less than 1% in ear­ly Tues­day trad­ing.

Kiniksa had been test­ing its can­di­date in 40 pa­tients with se­vere pneu­mo­nia and hy­per­in­flam­ma­tion re­lat­ed to Covid-19 and ran­dom­ized them in an open-la­bel fash­ion in­to the drug and place­bo arms at a 1-to-1 ra­tio. All the pneu­mo­nia pa­tients need­ed sup­ple­men­tal oxy­gen, half need­ed non-in­va­sive ven­ti­la­tion, and none re­quired me­chan­i­cal ven­ti­la­tion at the base­line, Kiniksa said.

In ad­di­tion, 26 of the 40 pa­tients were on cor­ti­cos­teroids such as dex­am­etha­sone and 30 had al­so been tak­ing Gilead’s Vek­lury (remde­sivir). Kiniksa fol­lowed the pa­tients for 60 days af­ter a sin­gle in­fu­sion of mavril­i­mum­ab.

Over­all, 12 of the 21 pa­tients tak­ing mavril­i­mum­ab, or 57.1%, were alive and off oxy­gen af­ter two weeks, com­pared to 9 of 19 pa­tients (47.4%) on place­bo. That marked a rel­a­tive in­crease of 20.5%, Kiniksa said, but clocked in at a nom­i­nal p-val­ue of p=0.536 — more than a full or­der of mag­ni­tude high­er than need­ed to prove sig­nif­i­cance.

The sec­ondary al­so failed to reach the mag­ic p=0.05 num­ber, though it’s here where the biotech is point­ing to­ward the pos­i­tive trend. Af­ter four weeks, 20 of 21 pa­tients were alive and not suf­fer­ing from res­pi­ra­to­ry fail­ure, com­pared to 15 of 19 in the place­bo group. Kiniksa’s rel­a­tive in­crease in this in­stance was 20.7%, which reg­is­tered a p-val­ue of p=0.172.

Kiniksa al­so pro­vid­ed da­ta re­gard­ing the deaths of pa­tients in both arms. Fol­low­ing the four-week sec­ondary end­point pe­ri­od, there was one death in the mavril­i­mum­ab arm and three on place­bo, good for a nom­i­nal p=0.222. Af­ter the full 60-day ob­ser­va­tion pe­ri­od, there was one ad­di­tion­al death in the place­bo group, which low­ered the nom­i­nal p-val­ue to 0.108.

Tues­day’s da­ta mark the lat­est in a string of ex­per­i­men­tal drugs re­pur­posed to fight Covid-19 that show ini­tial pos­i­tive signs of ef­fi­ca­cy but al­so pose as many ques­tion as they an­swer. Vek­lury has been the most promi­nent of the bunch, hav­ing demon­strat­ed a re­duc­tion in re­cov­ery time by five days in hos­pi­tal­ized Covid-19 pa­tients and by sev­en days in pa­tients re­quir­ing oxy­gen, in a NI­AID-spon­sored tri­al.

But the WHO has come out against Gilead’s drug, find­ing Vek­lury did not have any sub­stan­tial ef­fect on im­prov­ing mor­tal­i­ty rates, re­duc­ing the amount of pa­tients need­ing ven­ti­la­tors or short­en­ing hos­pi­tal stays. De­spite this, the FDA hand­ed down a full ap­proval for Vek­lury in Oc­to­ber and said it found the for­mer tri­al “bet­ter suit­ed” for a time-to-re­cov­ery end­point since the WHO study was open la­bel.

It re­mains to be seen whether Tues­day’s mavril­i­mum­ab da­ta will help or hurt its chances as a Covid-19 drug giv­en the ever-shift­ing land­scape of tack­ling the dis­ease. Mavril­i­mum­ab is a mon­o­clon­al an­ti­body that tar­gets GM-CS­FRα, hav­ing made it through a Phase IIb study for rheuma­toid arthri­tis. Kiniksa’s lead in­di­ca­tion for mavril­i­mum­ab is gi­ant cell ar­teri­tis, a rare in­flam­ma­to­ry dis­ease of medi­um-to-large ar­ter­ies.

The com­pa­ny is fur­ther eval­u­at­ing the pro­gram in Covid-19 in a glob­al, adap­tive de­sign Phase II/III tri­al, and is ex­pect­ing Phase II da­ta in the first half of next year.

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

So­cial: Kiniksa web­site

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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