Silviu Itescu, Mesoblast CEO

Mesoblast spins a PhI­II cell ther­a­py miss in heart fail­ure as a win, high­light­ing pos­i­tive mor­tal­i­ty da­ta

About two and a half months af­ter the FDA turned away their lead pro­gram, Mesoblast $MESO re­port­ed a Phase III miss Mon­day af­ter­noon for their sec­ond clin­i­cal prod­uct. But the Aus­tralian biotech point­ed to­ward da­ta in a sec­ondary end­point it thinks the agency might find promis­ing.

In a late-stage tri­al mea­sur­ing rexleme­stro­cel-L in 537 pa­tients, Mesoblast found that the ex­per­i­men­tal cell ther­a­py did not sig­nif­i­cant­ly re­duce hos­pi­tal­iza­tions over place­bo in in­di­vid­u­als with re­cur­ring heart fail­ure. The pro­gram man­aged to hit sec­on­daries in mor­tal­i­ty-rate re­duc­tion for ear­li­er stages of heart fail­ure, and it’s here where Mesoblast hopes it can still pave a path to­ward ac­cel­er­at­ed ap­proval should reg­u­la­tors prove re­cep­tive.

“The hos­pi­tal­iza­tions in pa­tients with chron­ic heart fail­ure are re­al­ly about their abil­i­ty to han­dle vol­ume loads and pa­tients who are brit­tle are not able to han­dle vol­ume loads very well,” CEO Sil­viu Ites­cu said in a con­fer­ence call Mon­day evening. “It ap­pears that our ther­a­py does not have any im­pact on those types of out­comes.”

In­vestors ap­peared skep­ti­cal of Mesoblast’s claims as the com­pa­ny’s shares fell af­ter the bell Mon­day and con­tin­ued to slide Tues­day morn­ing to down about 17%.

The Phase III tri­al ran­dom­ized pa­tients even­ly in­to the drug or place­bo arms. Mesoblast en­rolled 206 pa­tients with Class II heart fail­ure and 331 in­di­vid­u­als who had pro­gressed to Class III, a more se­vere form of the con­di­tion. In or­der to be in­clud­ed in the study, all pa­tients need­ed to have been hos­pi­tal­ized for heart fail­ure with­in nine months of start­ing treat­ment.

Mesoblast did not re­port any num­bers or a p-val­ue for the pri­ma­ry end­point, on­ly say­ing there was “no re­duc­tion” over place­bo in hos­pi­tal­iza­tions for re­cur­ring non-fa­tal heart fail­ure events.

In­stead, the com­pa­ny re­vealed its pos­i­tive sec­ondary end­point da­ta. In all pa­tients, rexleme­stro­cel-L showed a 60% re­duc­tion in heart at­tacks and stroke re­lat­ed to car­diac death, Mesoblast said, scor­ing a p-val­ue of  0.002. The ther­a­py al­so demon­strat­ed a 60% re­duc­tion in death from any cause in the Class II pop­u­la­tion, good for a p-val­ue of 0.037.

Rexleme­stro­cel-L al­so pre­vent­ed such pa­tients from pro­gress­ing to se­vere dis­ease but did not spec­i­fy any num­bers, the com­pa­ny said, on­ly re­port­ing a p-val­ue of 0.004. Those in the con­trol arm with max­i­mum stan­dard of care ther­a­py pro­gressed from Class II to Class III af­ter an av­er­age of 20 months.

It’s these da­ta where Mesoblast now sees a po­ten­tial path ahead. Ites­cu fur­ther told in­vestors in Mon­day’s call that rexleme­stro­cel-L could prove a com­ple­men­tary med­i­cine to drugs that re­duce hos­pi­tal­iza­tions but don’t re­duce mor­tal­i­ty. He al­so said in pre­vi­ous meet­ings with the FDA that the agency has made clear it is fo­cus­ing on mor­tal­i­ty, de­spite hos­pi­tal­iza­tion serv­ing as pri­ma­ry.

When the com­pa­ny start­ed its tri­al, Ites­cu said, the the­o­ry for the un­der­ly­ing mech­a­nism was that the med­i­cine could re­duce in­flam­ma­tion in heart mus­cles, pro­tect tis­sue from dy­ing and pre­vent those mus­cles from be­com­ing scar tis­sue.

“The ques­tion then goes to why do we have this ma­jor ben­e­fit on mor­tal­i­ty?” Ites­cu said on the call. “I think the da­ta that we’ve seen here, where we’ve seen this dra­mat­ic re­duc­tion in mor­tal­i­ty in pa­tients who are at an ad­vanced stage of dis­ease but not yet so ad­vanced that they’re not able to be res­cued, sug­gests that this mech­a­nism may be play­ing a key role.”

Ites­cu al­so not­ed the pro­gram’s ben­e­fits in less se­vere cas­es of heart fail­ure, say­ing it could po­ten­tial­ly be used to in­ter­vene be­fore pa­tients progress past Class II. The key mov­ing for­ward will be meet­ing with reg­u­la­tors and fig­ur­ing out ex­act­ly the right time to dose pa­tients.

Mon­day’s re­sults fol­low the FDA hand­ing Mesoblast a CRL for its acute graft-ver­sus-host dis­ease pro­gram, remestem­cel-L, back in Oc­to­ber. Reg­u­la­tors ob­ject­ed to the na­ture of the da­ta pack­age, with the com­pa­ny hop­ing to gain ap­proval on the ba­sis of on­ly a sin­gle, open-la­bel tri­al. De­spite the re­jec­tion, No­var­tis part­nered with the biotech last month in a $1.2 bil­lion-plus deal, hop­ing to de­vel­op the can­di­date for ARDS, in­clud­ing cas­es re­lat­ed to Covid-19.

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 is 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 is 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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David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

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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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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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

There are new questions being posed about a class of cancer drugs in the wake of the second FDA-enforced clinical hold in the field.

Two years after the FDA hit Amgen with a clinical hold on its MCL-1 inhibitor AMG 397 following signs of cardiac toxicity, AstraZeneca says that regulators hit them with a hold on their rival therapy of the same class.

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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Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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

Ex­clu­sive: Athi­ra CEO Leen Kawas re­signs af­ter in­ves­ti­ga­tion finds she ma­nip­u­lat­ed da­ta

Leen Kawas, CEO and founder of the Alzheimer’s upstart Athira Pharma, has resigned after an internal investigation found she altered images in her doctoral thesis and four other papers that were foundational to establishing the company.

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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Sen. Richard Durbin (D-IL, foreground) and Sen. Richard Blumenthal (D-CT) (Patrick Semansky/AP Images)

Sen­a­tors back FDA's plan to re­quire manda­to­ry pre­scriber ed­u­ca­tion for opi­oids

Three Senate Democrats are backing an FDA plan to require mandatory prescriber education for opioids as overdose deaths have risen sharply over the past decade, with almost 97,000 American opioid-related overdose deaths in the past year alone.

While acknowledging a decline in overall opioid analgesic dispensing in recent years, the FDA said it’s reconsidering the need for mandatory prescriber training through a REMS given the current situation with overdoses, and is seeking input on the aspects of the opioid crisis that mandatory training could potentially mitigate.

Bris­tol My­ers pledges to sell its Ac­celeron shares as ac­tivist in­vestors cir­cle Mer­ck­'s $11.5B buy­out — re­port

Just as Avoro Capital’s campaign to derail Merck’s proposed $11.5 billion buyout of Acceleron gains steam, Bristol Myers Squibb is leaning in with some hefty counterweight.

The pharma giant is planning to tender its Acceleron shares, Bloomberg reported, which add up to a sizable 11.5% stake. Based on the offer price, the sale would net Bristol Myers around $1.3 billion.

To complete its deal, Merck needs a majority of shareholders to agree to sell their shares.