FDA rais­es ques­tions about Mallinck­rodt's HRS-1 drug be­fore ad­vi­so­ry hear­ing

Last Au­gust, UK drug­mak­er Mallinck­rodt pre­sent­ed pos­i­tive topline find­ings for its em­bat­tled ter­li­pressin, il­lus­trat­ing the can­di­date met its pri­ma­ry end­point in treat­ing a life-threat­en­ing form of liv­er dis­ease that caus­es kid­ney fail­ure.

But the FDA con­tin­ues to have ques­tions about ter­li­pressin’s safe­ty and ef­fi­ca­cy. Af­ter de­ter­min­ing from the out­set of the tri­al that the pri­ma­ry end­point would on­ly clas­si­fy as a sur­ro­gate end­point, the agency is ques­tion­ing whether or not pa­tients “trend­ed to­ward clin­i­cal im­prove­ments” while on ter­li­pressin. Reg­u­la­tors will con­vene in a hear­ing to­day and have re­leased a doc­u­ment out­lin­ing their think­ing ahead of the meet­ing.

In par­tic­u­lar, the FDA high­light­ed “a sig­nif­i­cant safe­ty con­cern” re­gard­ing a high­er num­ber of pa­tients in the ter­li­pressin arm who suf­fered res­pi­ra­to­ry fail­ure than in the place­bo arm. More than half of these events oc­curred with­in five days of ad­min­is­ter­ing treat­ment and 61 per­cent re­sult­ed in death, com­pared to 20 per­cent in the con­trol.

The FDA did note that be­cause of the med­ical com­plex­i­ties in most of the pa­tients stud­ied, it is dif­fi­cult to de­ter­mine to what ex­tent, if any, the role ter­li­pressin played in each of the in­di­vid­ual cas­es. The agency is al­so con­cerned about an in­creased rate of sep­sis and sep­tic shock in the treat­ment arm.

Ter­li­pressin has faced sev­er­al chal­lenges in its quest to win ap­proval to treat he­pa­tore­nal syn­drome type 1 in the US ever since it re­ceived a com­plete re­sponse let­ter all the way back in 2009. At the time, the FDA re­quired Mallinck­rodt to con­duct an ad­di­tion­al study to prove the ef­fi­ca­cy and safe­ty of ter­li­pressin, but the fol­low-up again failed to reach sta­tis­ti­cal sig­nif­i­cance.

The third tri­al for ter­li­pressin, which the FDA is eval­u­at­ing in to­day’s hear­ing, did show a sta­tis­ti­cal­ly sig­nif­i­cant re­ver­sal in HRS-1 com­pared to the place­bo. Ad­di­tion­al­ly, due to high mor­tal­i­ty rates of HRS-1, pa­tients may some­times re­quire re­nal re­place­ment ther­a­py, and those in the ter­li­pressin arm showed high­er rates of RRT-free sur­vival de­spite ter­li­pressin treat­ment in com­bi­na­tion with RRT not show­ing an as­so­ci­a­tion with im­proved sur­vival.

But be­cause the pri­ma­ry end­point of the study cap­tured treat­ment ef­fects on a lab­o­ra­to­ry pa­ra­me­ter (serum cre­a­ti­nine), the agency con­sid­ered it a sur­ro­gate end­point. Whether or not the FDA ap­proves ter­li­pressin for use to treat HRS-1, in light of the tri­al meet­ing for that end­point, is up for de­bate. It’s worth not­ing that ter­li­pressin is ap­proved for use in Eu­rope un­der the brand name Gly­pressin.

HRS-1 is a life-threat­en­ing con­di­tion in­volv­ing a rapid de­cline in kid­ney func­tion in peo­ple with ad­vanced liv­er dis­ease. The ail­ment is most com­mon in in­di­vid­u­als with ad­vanced cir­rho­sis and as­cites, but can al­so oc­cur in some with acute liv­er fail­ure and oth­er liv­er dis­eases. Half of those with HRS-1 die with­in two weeks of di­ag­no­sis and 80 per­cent with­in three months.

Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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Lund­beck sounds taps on an­oth­er CNS drug, re­treat­ing from a mine field still oc­cu­pied by a Mer­ck team

Lundbeck has snipped another clinical-stage branch of its CNS research, dumping a schizophrenia program after determining that their therapy would have no positive influence on the disease.

Designed originally as a 240-patient study, researchers set out in early 2019 to see if a homegrown drug dubbed Lu AF11167 could make it through a proof-of-concept study. The drug is a PDE10Ai inhibitor, targeting an enzyme which it said at the time offered a new pathway to retuning the body’s neurotransmitter dopamine. The big idea was that by hitting their target, the drug would modulate “dopamine D1 and D2 receptor-mediated intraneuronal signaling without binding to these receptors,” influencing negative symptoms of schizophrenia.

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UP­DAT­ED: No­vavax her­alds the lat­est pos­i­tive snap­shot of ear­ly-stage Covid-19 vac­cine — so why did its stock briefly crater?

High-flying Novavax $NVAX became the latest of the Covid-19 vaccine players to stake out a positive set of biomarker data from its early-stage look at its vaccine in humans.

Their adjuvanted Covid-19 vaccine was “well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera,” the company noted. According to the biotech:

All subjects developed anti-spike IgG antibodies after a single dose of vaccine, many of them also developing wild-type virus neutralizing antibody responses, and after Dose 2, 100% of participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID‑19 disease. Importantly, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional.

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J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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Sean Nolan and RA Session II

Less than 3 months af­ter launch, the AveX­is crew’s Taysha rais­es $95M Se­ries B. Is an IPO next?

The old AveXis team is moving quickly in Dallas.

Three months ago, they launched Taysha with $30 million in Series A funding and a pipeline of gene therapies out of UT Southwestern. Now, they’ve announced an oversubscribed $95 million Series B. And the biotech is declining all interview requests on the news, the kind of broad silence that can indicate an IPO is in the pipeline.

Biotechs, including those relatively fresh off launch, have been going public at a frenzy since the pandemic began. Investors have showed a willingness to put upwards of $200 million to companies that have yet to bring a drug into the clinic. Still, if Taysha were to go public in the near future, it would be perhaps the shortest path from launch to IPO in recent biotech memory.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

Mod­er­na CEO Stéphane Ban­cel out­lines a prospec­tive moth­er­lode of Covid-19 vac­cine rev­enue — will a back­lash fol­low?

Moderna shows no sign of slowing down, or turning charitable when it comes to pricing supplies of its Covid-19 vaccine.

One of the leaders in the Phase III race to get a Covid-19 vaccine across the finish line in record time, Moderna says it’s on track to complete enrollment in one of the most avidly watched studies in the world next month. And the biotech has already banked some $400 million in deposits for vaccine supply as it works through negotiations with countries around the world — as CEO Stéphane Bancel sets out to hire a commercial team.

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Covid-19 roundup: J&J and BAR­DA agree to $1 bil­lion for 100 mil­lion dos­es; Plas­ma re­duces mor­tal­i­ty by 50% — re­ports

J&J has become the latest vaccine developer to agree to supply BARDA with doses of their Covid-19 vaccine, signing an agreement that will give the government 100 million doses in exchange for $1 billion in funding.

The agreement, similar to those signed by Novavax, Sanofi and AstraZeneca-Oxford, provides funding not only for individual doses but to help J&J ramp up manufacturing. Pfizer, by contrast, received $1.95 billion for the doses alone. Still, if one looked at each agreement as purchase amounts, J&J’s deal would be $10 per dose, slotting in between Novavax’s $16 per dose and AstraZeneca’s $4 per dose.

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RA, No­var­tis back Gen­tiBio's seed round, plans to launch de­vel­op­ment of En­gTreg ther­a­pies

Boston, MA-based startup GentiBio landed a $20 million seed fund from three investors to dive into engineered regulatory T cell (EngTreg) development.

Marquee investors OrbiMed, Novartis Venture Fund and RA Capital Management have backed GentiBio’s mission to develop EngTregs for the treatment of autoimmune, alloimmune, autoinflammatory, and allergic diseases. Unlike other companies studying treatments using a patient’s own Tregs, GentiBio plans to make use of CD4+ immune cells, found in the blood.

Paul Laikind, ViaCyte CEO

Stem cell play­er Vi­a­Cyte ex­pands col­lab­o­ra­tion with Gore to de­vel­op sub­cu­ta­neous di­a­betes treat­ment

Longtime stem cell player ViaCyte has teamed up with a materials science company in an effort to solve immunosuppression challenges and advance its type 1 diabetes treatments.

Expanding on an existing collaboration, ViaCyte and W.L. Gore have agreed to combine the biotech’s PEC-Encap candidate with a Gore-produced membrane in what they hope will eliminate the need for immunosuppressive drugs. Such treatments have created foreign body responses in the past, and stamping these reactions out is the main goal, ViaCyte CEO Paul Laikind said.