Zyner­ba flunks an­oth­er ma­jor tri­al, all but end­ing Frag­ile X hopes

Zyner­ba’s CBD drug has failed its fourth tri­al in as many years.

In a piv­otal Phase III tri­al, their lead com­pound failed to sig­nif­i­cant­ly im­prove be­hav­ioral symp­toms in pa­tients with Frag­ile X syn­drome, miss­ing both the pri­ma­ry end­point and three dif­fer­ent sec­ondary end­points.

The fail­ure is the lat­est in a se­ries of set­backs for a com­pa­ny that once hoped to ri­val top cannabis biotech GW Phar­ma. Five years ago, as CBD drug de­vel­op­ment be­gan bub­bling, the Penn­syl­va­nia biotech went pub­lic on the promise of mak­ing THC, cannabis’s ac­tive in­gre­di­ent, with­out the need for plants, al­low­ing for cheap­er, more scal­able drugs. In giv­ing the drug by gel rather than oral­ly, they al­so promised to re­duce side ef­fects.

Since then, though, while GW Phar­ma emerged with the first CBD ap­proval, Zyner­ba’s drugs have strug­gled might­i­ly in the clin­ic, miss­ing key end­points and some­times fail­ing to show dose-de­pen­dent re­spons­es. Plans for an epilep­sy and os­teoarthri­tis drug fell away with clin­i­cal fail­ures in 2017. A year lat­er, so did a patch that was meant to de­liv­er their THC through the skin.

Zyner­ba’s note­wor­thy suc­cess was a Phase II tri­al that seemed to show a 46% im­prove­ment in symp­toms among 20 pa­tients with the ge­net­ic neu­ro­log­i­cal dis­or­der Frag­ile X. That tri­al, though, had no con­trol arm, leav­ing doubts about how ef­fec­tive the drug was.

The 212-per­son tri­al an­nounced Tues­day was the first place­bo-con­trolled study to test Zyner­ba’s CBD for that con­di­tion, and the study ap­peared to vin­di­cate the doubters. Pa­tients on the drug did not score sig­nif­i­cant­ly bet­ter on the aber­rant be­hav­ior check­list, the ir­ri­tabil­i­ty sub­scale, the so­cial­ly un­re­spon­sive/lethar­gic sub­scale, or in Clin­i­cal Glob­al Im­pres­sion.

The com­pa­ny’s stock was cut near­ly in half Tues­day morn­ing, from $6.54 to $3.48.

Ar­man­do Anido

As he has af­ter past fail­ures, CEO Ar­man­do Anido tried to spin the lone pos­i­tive re­sult of the tri­al in­to a vic­to­ry. Al­though it wasn’t a pri­ma­ry or sec­ondary end­point, the com­pa­ny pre-planned an analy­sis of the pa­tients whose FMR1 gene — the or­ches­tral gene in Frag­ile X — and were ful­ly methy­lat­ed.  In those pa­tients, the re­sults were sta­tis­ti­cal­ly sign­fi­ciant, al­beit nar­row­ly so.

“The re­sults from CON­NECT-FX iden­ti­fied a sig­nif­i­cant pa­tient pop­u­la­tion who re­spond­ed well to Zygel and may pro­vide us with a path­way to­wards li­cen­sure,” CEO Ar­man­do Anido said in a state­ment, not­ing they es­ti­mate around 60% of frag­ile X pa­tients are ful­ly methy­lat­ed. “We in­tend to dis­cuss the re­sults of the study with the FDA as soon as pos­si­ble.”

The com­pa­ny said sim­i­lar things af­ter the os­teoarthri­tis tri­al pro­duced one pos­i­tive re­sult on a com­pos­ite end­point. The in­di­ca­tion is no longer list­ed on their of­fi­cial pipeline.

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.