One year on, Capri­cor's stem cell ther­a­py ap­pears to help DMD pa­tients in small study, but in­vestors balk at the da­ta

Re­peat­ed set­backs aside, lit­tle Capri­cor has sug­gest­ed it has gen­er­at­ed some long-term da­ta to sup­port its pur­suit to gar­ner ap­proval for its stem cell ther­a­py for Duchenne mus­cu­lar dy­s­tro­phy, al­though some of the da­ta ap­peared to un­der­whelmed in­vestors.

The da­ta from the small, place­bo-con­trolled mid-stage study, HOPE-2, tracked the ef­fects of the com­pa­ny’s stem cell ther­a­py CAP-1002, which is de­signed to tem­per the in­flam­ma­tion as­so­ci­at­ed with DMD, in 8 boys and young men who are in ad­vanced stages of DMD. The re­main­ing 12 en­rolled pa­tients re­ceived the place­bo.

The main goal of the study was a mea­sure that eval­u­ates shoul­der, arm and hand strength in pa­tients who are gen­er­al­ly non-am­bu­lant (per­for­mance of the up­per limb (PUL) 2.0), as sug­gest­ed by the FDA, Capri­cor said. It is one of sev­er­al ways Capri­cor quan­ti­fied skele­tal mus­cle im­prove­ment in the tri­al.

The in­tra­venous in­fu­sion of CAP-1002, giv­en every 3 months, in­duced a sta­tis­ti­cal­ly mean­ing­ful im­prove­ment of 2.4 points (p=0.05) ver­sus the place­bo group, in which pa­tient de­clines were con­sis­tent with nat­ur­al his­to­ry da­ta. How­ev­er, on an­oth­er mea­sure of up­per limb func­tion, the trend was in fa­vor of the Capri­cor drug, but did not hit sta­tis­ti­cal sig­nif­i­cance.

The com­pa­ny’s shares $CAPR were down near­ly 13% to $6.89 in morn­ing trad­ing.

Source: Capri­cor, 2020

Click on the im­age to see the full-sized ver­sion

Mean­while, there were al­so some en­cour­ag­ing da­ta on car­diac func­tion — the ge­net­ic con­di­tion is char­ac­ter­ized by pro­gres­sive weak­ness and chron­ic in­flam­ma­tion of the skele­tal, heart and res­pi­ra­to­ry mus­cles.

As re­flect­ed above, CAP-1002 elicit­ed an im­prove­ment across dif­fer­ent mea­sures of car­diac func­tion, al­though the ef­fect was not al­ways sta­tis­ti­cal­ly sig­nif­i­cant. In par­tic­u­lar, the drug al­so caused a re­duc­tion in the lev­els of the bio­mark­er CK-MB, an en­zyme that is on­ly re­leased when there is car­diac mus­cle cell dam­age.

Armed with these da­ta and an RMAT and or­phan drug des­ig­na­tion from the FDA, Capri­cor is now hop­ing to eke out a plan with the FDA for mar­ket­ing ap­proval.

Ed­uar­do Mar­bán

LA-based Capri­cor ini­tial­ly set out to test the po­ten­tial of tech­nol­o­gy that Ed­uar­do Mar­bán, CEO Lin­da Mar­bán’s hus­band, de­vel­oped at Johns Hop­kins. But re­peat­ed set­backs clob­bered the com­pa­ny, which in 2014 trad­ed north of $14 a share. In 2017, J&J walked away from a col­lab­o­ra­tion on a stem cell ther­a­py for dam­aged hearts af­ter it flopped in the clin­ic.

In late 2018, the com­pa­ny vol­un­tar­i­ly halt­ed a DMD clin­i­cal tri­al, fol­low­ing a “se­vere al­ler­gic re­ac­tion” that oc­curred dur­ing in­fu­sion. In Feb­ru­ary 2019, the com­pa­ny said it is ex­plor­ing strate­gic al­ter­na­tives for one or more of its prod­ucts and cut­ting 21 jobs to keep fi­nan­cial­ly afloat, but had re­sumed dos­ing in its DMD tri­al.

The first batch of pos­i­tive da­ta on CAP-1002, which con­sists of prog­en­i­tor cells de­rived from donor hearts and is de­signed to ex­ude ex­o­somes that ini­ti­ate mus­cle re­pair by sup­press­ing in­flam­ma­tion and dri­ving im­munomod­u­la­tion, came last Ju­ly when the com­pa­ny an­nounced the drug had gen­er­at­ed a pos­i­tive ef­fect at the in­ter­im analy­sis junc­ture of HOPE-2. Capri­cor is now work­ing on to flex­ing its ther­a­peu­tic mus­cle with CAP-1002 to fight the Covid-19 pan­dem­ic.

DMD is a rare mus­cle-wast­ing dis­ease caused by the ab­sence of dy­s­trophin, a pro­tein that helps keep mus­cle cells in­tact. It dis­pro­por­tion­ate­ly af­fects boys — and af­fects rough­ly 6,000 in the Unit­ed States.

Pa­tients are es­sen­tial­ly treat­ed with steroids. Sarep­ta Ther­a­peu­tics now has two ex­on-skip­ping drugs de­signed to treat cer­tain sub­sets of the dis­ease, al­though the mag­ni­tude of their ef­fect is con­tro­ver­sial giv­en that ap­provals were not based on place­bo-con­trolled da­ta. Mean­while, Sarep­ta and oth­ers are al­so pur­su­ing one-time cures in the form of gene ther­a­pies to re­place the miss­ing dy­s­trophin gene in pa­tients.

So­cial: Lin­da Mar­bán, Capri­cor CEO (Twit­ter)

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 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.