UK biotech rock­ets up on Covid-19 'break­through' for in­haled in­ter­fer­on be­ta — can its small study live up to the boast?

In­ter­fer­on be­ta, a cy­tokine ap­proved and wide­ly used in in­jectable forms, sur­faced very ear­ly on as a po­ten­tial treat­ment for Covid-19. A British biotech now says its in­haled for­mu­la­tion of the drug helped hos­pi­tal­ized pa­tients re­cov­er — and low­ered their risk of do­ing worse.

It’s a small study in­volv­ing on­ly 101 pa­tients and missed some end­points, but Synair­gen said the re­sults could sig­nal a “ma­jor break­through.” If true, that would al­so mark se­ri­ous val­i­da­tion for a drug that As­traZeneca once li­censed but even­tu­al­ly aban­doned as an asth­ma ther­a­py.

First, the pos­i­tives:

  • Pa­tients in the SNG001 arm saw their risk of re­quir­ing ven­ti­la­tion or dy­ing re­duced by 79% com­pared to those who re­ceived place­bo, with a mar­gin­al­ly pos­i­tive p-val­ue of 0.046.
  • They were al­so “more than twice as like­ly to re­cov­er” — to the point where they can go about their dai­ly lives de­spite the in­fec­tion — al­though the dif­fer­ence here wasn’t spelled out (p=0.043).
Stephen Hol­gate

Al­though the com­pa­ny didn’t use the ex­act word­ing, these out­comes ap­pear to align with the pri­ma­ry end­point list­ed on a tri­al post­ing, which mea­sures clin­i­cal im­prove­ment dur­ing the 16-day dos­ing pe­ri­od on an 8-point scale. No fur­ther de­tails on how pa­tients im­proved or wors­ened along that scale were pro­vid­ed.

Shares shot up 173.97% up­on the news, reach­ing 100 GBX on the Lon­don Stock Ex­change.

One oth­er sec­ondary end­point stood out, while oth­ers fell short.

Breath­less­ness, a se­vere symp­tom de­signed to be as­sessed along­side cough and spu­tum, was “marked­ly re­duced” for pa­tients who got the drug (p=0.007). The num­bers for cough and spu­tum weren’t avail­able.

More­over, Synair­gen not­ed, three par­tic­i­pants died af­ter be­ing ran­dom­ized to place­bo, com­pared to ze­ro deaths in the SNG001 group — not that they can draw any con­clu­sion from it.

SNG001 works by send­ing high lo­cal con­cen­tra­tions of in­ter­fer­on be­ta, a “nat­u­ral­ly oc­cur­ring an­tivi­ral pro­tein,” to re­store the lung’s de­fense against the virus, ac­cord­ing to Stephen Hol­gate, a Uni­ver­si­ty of Southamp­ton pro­fes­sor who co-found­ed Synair­gen.

Richard Mars­den

But the tri­al, which was con­duct­ed across 9 sites in the UK, found that pa­tients who al­ready re­quired oxy­gen at ad­mis­sion didn’t seem to ben­e­fit as much. The “nu­mer­i­cal ad­van­tage” in the like­li­hood of hos­pi­tal dis­charge didn’t trans­late to a sta­tis­ti­cal­ly sig­nif­i­cant gain, with me­di­an time to dis­charge in the SNG001 group at 6 days and the place­bo group, 9 days (p=0.096).

Synair­gen al­so want­ed to high­light that pa­tients ap­peared to be more like­ly to have re­cov­ered by the end of treat­ment if they were on the drug, though it was again not sta­tis­ti­cal­ly sig­nif­i­cant.

What does this all mean? The com­pa­ny is con­duct­ing fur­ther analy­sis and it has pre­vi­ous­ly said a piv­otal tri­al would be need­ed. Mars­den said they are now work­ing with reg­u­la­tors and oth­er groups to “progress this po­ten­tial COVID-19 treat­ment as rapid­ly as pos­si­ble.”

It’s un­clear how the da­ta and those from a fol­low-up tri­al would be squared against in­ter­fer­on be­ta ad­min­is­tered in more tra­di­tion­al, com­mer­cial­ly avail­able forms. These are be­ing test­ed in com­bi­na­tion with the HIV drug Kale­tra in both the UK’s RE­COV­ERY tri­al and the WHO-led SOL­I­DAR­I­TY study, two of the largest mas­ter pro­to­cols or­ga­nized to weed out a ros­ter of po­ten­tial Covid-19 drugs.

A study out of Is­rael, pub­lished days ago, con­clud­ed that al­though in­ter­fer­on be­ta “did not change time to reach the clin­i­cal re­sponse, adding to the stan­dard of care sig­nif­i­cant­ly in­creased dis­charge rate on day 14 and de­creased 28-day mor­tal­i­ty.”

Be­fore the pan­dem­ic swept it up, Synair­gen had been test­ing SNG001 in pa­tients with chron­ic ob­struc­tive pul­monary dis­ease. Back in 2014 As­traZeneca in-li­censed the drug for asth­ma and kicked off a study, on­ly to halt it ear­ly in 2016 af­ter de­ter­min­ing that an over­all low num­ber of ex­ac­er­ba­tions among the asth­ma pa­tients re­cruit­ed in that cold sea­son would make it dif­fi­cult to see if they could ac­tu­al­ly hit the pri­ma­ry end­point that had been laid out.

“When we’ve col­lect­ed cells from pa­tients with COPD and asth­ma and old­er peo­ple…we find that their lung cells don’t re­spond very well to virus­es,” Mars­den told End­points News in a pre­vi­ous in­ter­view. “We have al­so along the way al­ways rec­og­nized that with an emerg­ing virus, the drug could be used.”

Whether it will be adopt­ed is a whole oth­er ques­tion like­ly won’t take long to an­swer in the fran­tic R&D race for treat­ments.

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

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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.

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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

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

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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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Pascal Soriot, AstraZeneca CEO (via Getty images)

UP­DAT­ED: FDA slaps As­traZeneca's MCL-1 can­cer drug with a hold af­ter safe­ty is­sue — 2 years af­ter Am­gen axed a trou­bled ri­val

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The pharma giant noted on clinicaltrials.gov that its Phase I/II study for the MCL-1 drug AZD5991 “has been put on hold to allow further evaluation of safety related information.”

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

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