Savara gets FDA break­through sta­tus de­spite large, late-stage fail­ure

Savara watched their stock crater in June as they an­nounced a late-stage fail­ure on their lead com­pound. But now, based on the same Phase III tri­al, the FDA is giv­ing the biotech and its rare lung dis­ease drug break­through ther­a­py des­ig­na­tion.

The des­ig­na­tion comes for Mol­gradex, an in­halant meant to treat au­toim­mune pul­monary alve­o­lar pro­teinosis (aPAP). It was the lead com­pound in Savara’s 2016 buy­out of Seren­dex. The dis­ease is caused by au­toan­ti­bod­ies that neu­tral­ize a pro­tein called GM-CSF in the lungs, and the in­halant re­plen­ish­es the lungs with a re­com­bi­nant form of the pro­tein.

Savara said in June that the drug had failed to sig­nif­i­cant­ly im­prove oxy­gen lev­els in tri­al pa­tients’ alve­o­lar, the parts of the lung ob­struct­ed in PAP pa­tients. Savara tried to sal­vage the study, point­ing to sec­ondary and “ex­plorato­ry” end­points and blam­ing the pri­ma­ry fail­ure on an un­ex­pect­ed­ly high place­bo ef­fect. In­vestors didn’t buy it, tank­ing their stock price $SVRA 75%.

The FDA, though, ap­pears to think there’s a sto­ry there. It’s im­pos­si­ble to know the agency’s think­ing, but de­tailed slides Savara re­leased this fall em­pha­sized “a pat­tern of im­prove­ment” on sev­er­al met­rics in the 139-per­son tri­al and ar­gued that the “to­tal­i­ty of out­come da­ta” sup­port Mol­gradex over place­bo.

That da­ta in­clud­ed sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments on the Saint Georges Res­pi­ra­to­ry Ques­tion­naire and CT scans. The biotech al­so ar­gued the pri­ma­ry end­point (tech­ni­cal­ly called A-aDO2), as well as a walk­ing test called 6MWT, he­mo­glo­bin lev­els and the time be­fore res­cue surgery “trend­ed” to­ward sig­nif­i­cance.

Bruce Trap­nell

Mol­gradex was “ef­fec­tive as shown by changes in lung pathol­o­gy, phys­i­ol­o­gy, health sta­tus, func­tion,” lead in­ves­ti­ga­tor Bruce Trap­nell wrote.

That still leaves a lot of ques­tions about the ben­e­fit for pa­tients, and though in­vestors came back with the break­through des­ig­na­tion, they didn’t re­turn Savara to its pre-June sta­tus. The stock near­ly tripled on Mon­day, from $1.73 per share to $4.91. But that’s still less than half of the $10.57 price on June 12.

The news may al­so bol­ster con­fi­dence in Savara’s oth­er pro­grams. Those in­clude a Phase II tri­al ap­ply­ing Mol­gradex to non­tu­ber­cu­lous my­cobac­te­ria, with re­sults ex­pect­ed ear­ly this year, and a now-en­rolling study ap­ply­ing the drug to non­tu­ber­cu­lous my­cobac­te­ria in cys­tic fi­bro­sis pa­tients. There’s al­so a van­comycin in­halant for MR­SA in­fec­tions in CF pa­tients, with Phase III re­sults ex­pect­ed in about a year.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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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 are 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 are 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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Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Oc­u­lar Ther­a­peu­tix ham­mered by a PhII fail­ure in dry eye dis­ease — shares tank

Ocular Therapeutix $OCUL has had its ups and downs in the 7 years since it went public. Friday was one of those down days.

The Bedford, MA-based biotech reported that its lead experimental eye drug, OTX-CSI (cyclosporine intracanalicular insert), failed a Phase II trial for dry eye disease. And the stock experienced one of its periodic meltdowns, dropping more than 30% ahead of the bell.

The therapy flat failed the primary endpoint: increased tear production at 12 weeks as measured by the Schirmer’s Test compared to the vehicle control group. And while investigators called out an improvement from baseline in “signs of dry eye disease as measured by total corneal fluorescein staining (CFS) and symptoms of dry eye disease as measured by the visual analogue scale (VAS) eye dryness in subjects treated with the OTX-CSI insert,” it wasn’t statistically significant.

Sanofi, Re­gen­eron etch out an­oth­er PhI­II vic­to­ry for Dupix­ent, eas­ing se­vere itch and clear­ing le­sions

Sanofi and Regeneron can boast of another inflammatory disease where Dupixent has proven effective.

The best-selling drug, which targets both IL-4 and IL-13, has delivered a clean sweep in a Phase III trial for prurigo nodularis, a chronic disease characterized by itch so intense that it can affect patients’ sleep and psychology. Thick skin lesions can cover most of the body.

On the primary endpoint, 37% of patients taking Dupixent saw a clinically meaningful reduction in itch compared to 22% of those on placebo (p=0.0216) at week 12. All secondary endpoints were also met, including clearance of skin lesions and improvement in quality of life.