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.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Pfiz­er, Sarep­ta and two oth­ers sug­gest Duchenne drug safe­ty is­sues tied to "class ef­fect"

Since the first experimental Duchenne gene therapy programs came about, the space has proven rife with safety issues and patient deaths in clinical trials. Pfizer and three biotechs now think they’ve found a reason why.

The four companies suggested there may be a “class effect” causing the adverse events in Duchenne gene therapies, they wrote in a new study. They specifically highlighted how side effects in five patients across three trials, who all showed muscle weakness with cardiac involvement, were “strikingly similar.”

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Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

Frank Pallone (D-NJ), House Energy and Commerce Committee chair (Kevin Dietsch/Pool via AP Images)

House com­mit­tee unan­i­mous­ly ad­vances FDA user fee leg­is­la­tion with ac­cel­er­at­ed ap­proval tweaks

The House Energy and Commerce Committee on Wednesday offered a rare show of bipartisan support for a bill that would provide the FDA with user fees for the next five years.

The committee voted 55-0 to advance the quinquennial user fee bill to the full House floor, which if approved, will allow the FDA to use biopharma funds to hire new reviewers, and hit new marks as outlined in the user fee deals that the FDA and biopharma companies forged over the past several years.

Pearl Huang, former Cygnal Therapeutics president and CEO

UP­DAT­ED: Flag­ship builds a new start­up out of pieces from 2 of its biotechs. And a Roche vet leaves to do some­thing new

Flagship has crafted a new startup out of pieces from a pair of fledglings in the VC’s nest. And a prominent Roche veteran who ran one of the biotechs won’t be making the next leg of the journey.

The new company is called Sonata Therapeutics, which is picking up the work that Inzen was doing related to the cellular microenvironment and combining with Flagship’s Cygnal Therapeutics, which came out of stealth more than 3 years ago and put Pearl Huang — the BeiGene founder and former Roche SVP — at the helm.

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Patty Murray (D-WA) (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

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FDA lob­bies Con­gress over rare dis­ease court rul­ing with wide im­pli­ca­tions

Usually reserved for making decisions on drug applications or enforcing what Congress stipulates, the FDA is now dipping its toe into the wild world of congressional politics as it attempts to fix a major court decision that could have a chilling effect on rare disease R&D.

The case in question from last October saw a US appeals court overturn a prior FDA court win, saying that the agency never should’ve approved a rare disease drug because a previously approved but more expensive drug with the same active ingredient has orphan drug exclusivity barring such an approval.

Peter Marks (Greg Nash/Pool via AP)

Even FDA's Pe­ter Marks is wor­ried about the com­mer­cial vi­a­bil­i­ty of gene and cell ther­a­pies

When bluebird bio’s gene therapy to treat beta thalassemia won European approval in 2019, the nearly $2 million per patient price tag for the potential cure seemed like a surmountable hurdle.

Fast forward two years later, and bluebird has withdrawn Zynteglo, the beta thal drug, along with the rest of its gene therapy portfolio from Europe, which the company said is generally unwilling to pay a fair price for the treatment.

Pri­cy in­halers re­main ex­pen­sive due to de­vice tweaks that keep com­peti­tors at bay, re­searchers find

New research published in Health Affairs today highlights the way in which the FDA’s inhaler regulations have rewarded incremental adjustments to older products, thereby enabling companies to skirt around cheaper competition.

A DC appeals court clerk and researchers from Harvard and the University of Calgary dug through all the patents and regulatory exclusivities granted to inhalers approved by the FDA between 1986 and 2020, finding that of the 62 inhalers approved, 53 (or 85%) were brand-name products, with a median of 16 years of protection from generic competition.