Avro­bio takes a sec­ond stab at a good first im­pres­sion — but dura­bil­i­ty ques­tions still dog gene ther­a­py

Ge­off MacK­ay

Four months ago, Avro­bio’s shares $AVRO were sub­ject­ed to a rit­u­al slaugh­ter on Wall Street af­ter in­vestors were spooked by their lead gene ther­a­py’s poor per­for­mance on a key mea­sure re­flect­ing po­ten­tial dura­bil­i­ty. To­day, the top ex­ecs at the com­pa­ny are mak­ing a new pitch, hop­ing that they can win over the mar­ket with up­dat­ed ev­i­dence that the gene ther­a­py is work­ing for pa­tients with Fab­ry dis­ease.

But you can ex­pect plen­ty of more ques­tions to come on its longterm prospects.

The big ques­tion last Oc­to­ber was cen­tered on the vec­tor copy num­bers re­flect­ed in the hand­ful of pa­tients who had re­ceived Avro­bio’s AVR-RD-01. The VCN is a mark­er for the gene ther­a­py’s abil­i­ty to in­sert healthy copies of the GLA gene that en­codes for a de­fi­cient en­zyme in Fab­ry dis­ease. And it has to be right in a field pur­su­ing once-and-done treat­ments. Blue­bird went back to the draw­ing board af­ter track­ing VCN num­bers of 0.3 and 0.6 in the first gen­er­a­tion of its gene ther­a­py for be­ta-tha­lassemia, herald­ing a spike to 1.5 and 2.1 for two pa­tients in a Lenti-Glo­bin study. And blue­bird knows full well that a high­er, or ris­ing, VCN breeds con­fi­dence.

In Avro­bio’s case, the VCN head­ed down in sev­er­al cas­es. And their re­lease un­der­scores that adding a few months of ob­ser­va­tion didn’t im­prove mat­ters.  

Ac­cord­ing to CEO Ge­off MacK­ay, who de­cid­ed to add the VCN num­bers to this morn­ing’s re­lease in­stead of wait­ing for the evening pre­sen­ta­tion of the da­ta for an­a­lysts, this was all “as ex­pect­ed.” Pa­tient #1’s VCN, he said in an email, is “sta­ble” at 0.1.

In the Oc­to­ber re­sults we saw:

Pa­tient #1 start­ed ther­a­py with a VCN of 0.7 and then re­searchers tracked a steady drop to 0.1 18 months post-treat­ment. Pa­tient #2 dropped from 1.4 to 0.4 in 6 months. Pa­tient #3: 0.2 to 0.8 at 3 months. And pa­tient #4 went from 0.7 to 0.5 in a few months.

In the up­date to­day Pa­tient #1’s VCN is still at 0.1 22 months af­ter treat­ment. Pa­tient #2 is still at 0.4 at 12 months and Pa­tient #3 dropped to 0.5 at 6 months. Pa­tient #1 in the Phase II is at 0.2 at 6 months, drop­ping from 0.5 at 3 months af­ter start­ing out at 0.2.

The biotech set out to high­light the bio­mark­er ev­i­dence to back up their ther­a­py’s abil­i­ty to sub­sti­tute the chron­ic use of en­zyme re­place­ment ther­a­py for Fab­ry. The com­pa­ny not­ed:

All (evalu­able) pa­tients with re­port­ed da­ta ex­hib­it AGA en­zyme ac­tiv­i­ty above the di­ag­nos­tic range for males with clas­sic Fab­ry dis­ease af­ter re­ceiv­ing AVR-RD-01, in­clud­ing at 22 months for Pa­tient 1 of the Phase 1 study.

Two of the pa­tients in the Phase I have sus­pend­ed use of ERT.

We’ll see how in­vestors think about that now. But you can ex­pect plen­ty of ques­tions ahead on moves the com­pa­ny is mak­ing to im­prove the VCN rank­ings.

As of yes­ter­day’s close Avro­Bio’s shares were down 70% from their high of $51 last fall. The stock was tread­ing wa­ter at the open this morn­ing, slight­ly in the red dur­ing mid-morn­ing trad­ing.

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AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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Ab­b­Vie wins an ap­proval in uter­ine fi­broid-as­so­ci­at­ed heavy bleed­ing. Are ri­vals My­ovant and Ob­sE­va far be­hind?

Women expel on average about 2 to 3 tablespoons of blood during their time of the month. But with uterine fibroids, heavy bleeding is typical — a third of a cup or more. Drugmakers have been working on oral therapies to try and stem the flow, and as expected, AbbVie and their partners at Neurocrine Biosciences are the first to make it across the finish line.

Known chemically as elagolix, the drug is already approved as a treatment for endometriosis under the brand name Orilissa. It targets the GnRH receptor to decrease the production of estrogen and progesterone.

Paul Hudson, Sanofi CEO (Getty Images)

Sanofi CEO Paul Hud­son has $23B burn­ing a hole in his pock­et. And here are some hints on how he plans to spend that

Sanofi has reaped $11.1 billion after selling off a big chunk of its Regeneron stock at $515 a share. And now everyone on the M&A side of the business is focused on how CEO Paul Hudson plans to spend it.

After getting stung in France for some awkward politicking — suggesting the US was in the front of the line for Sanofi’s vaccines given American financial support for their work, versus little help from European powers — Hudson now has the much more popular task of managing a major cash cache to pull off something in the order of a big bolt-on. Or two.

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Sanofi brings in 4 new ex­ec­u­tives in con­tin­ued shake-up, as vac­cines and con­sumer health chief head out the door

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The company also said today that Alan Main, the head of their consumer healthcare unit, is out, and they named 4 executives to fill new or newly vacated positions, 3 of whom come from both outside both Sanofi and from Pharma.

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Pablo Legorreta, founder and CEO of Royalty Pharma AG, speaks at the annual Milken Institute Global Conference in Beverly Hills, California (Patrick T. Fallon/Bloomberg via Getty Images)

Cap­i­tal­iz­ing Pablo: The world’s biggest drug roy­al­ty buy­er is go­ing pub­lic. And the low-key CEO di­vulges a few se­crets along the way

Pablo Legorreta is one of the most influential players in biopharma you likely never heard of.

Over the last 24 years, Legorreta’s Royalty Pharma group has become, by its own reckoning, the biggest buyer of drug royalties in the world. The CEO and founder has bought up a stake in a lengthy list of the world’s biggest drug franchises, spending $18 billion in the process — $2.2 billion last year alone. And he’s become one of the best-paid execs in the industry, reaping $28 million from the cash flow last year while reserving 20% of the cash flow, less expenses, for himself.

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Roger Perlmutter, Merck R&D chief (YouTube)

Backed by BAR­DA, Mer­ck jumps in­to Covid-19: buy­ing out a vac­cine, part­ner­ing on an­oth­er and adding an­tivi­ral to the mix

Merck execs are making a triple play in a sudden leap into the R&D campaign against Covid-19. And they have more BARDA cash backing them up on the move.

Tuesday morning the pharma giant simultaneously announced plans to buy an Austrian biotech that has been working on a preclinical vaccine candidate, added a collaboration on another vaccine with the nonprofit IAVI and inked a deal with Ridgeback Biotherapeutics on an early-stage antiviral.

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Ear­ly sur­vival da­ta boost Zio­phar­m's 'con­trolled IL-12' im­munother­a­py for glioblas­toma

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Both the treatment and its developer, Ziopharm Oncology, have come a long way. The stock price peaked in 2015 but cratered in 2016 following a patient death in a Phase I.

As­traZeneca’s $7B ADC suc­ceeds where Roche failed, im­prov­ing sur­vival in gas­tric can­cer

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The antibody-drug conjugate AstraZeneca promised up-to $7 billion to partner on has had a quite a few months, beginning with splashy results in a Phase II breast cancer trial, a rapid approval and, earlier this month, breakthrough designations in both non-small cell lung cancer and gastric cancer.

Now, at ASCO, the British pharma and their Japanese partner, Daiichi Sankyo, have shown off the data that led to the gastric cancer designation, which they’ll take back to the FDA. In a pivotal, 187-person Phase II trial, Enhertu shrunk tumors in 42.9% of third-line patients with HER2-positive stomach cancer, compared with 12.5% in a control arm where doctors prescribed their choice of therapy. Progression-free survival was 5.4 months for Enhertu compared to 3.5 months for the control.

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Back in 2016, when then-Shire CEO Flemming Ørnskov picked up a promising clinical-stage IBD drug from Pfizer, the Boston-based biotech dubbed it SHP647 and moved it into the gem section of the pipeline, with rosy expectations of registration-worthy Phase III data ahead.

This was a drug that the EC wanted Takeda to commit to selling off before it gave their blessing to its acquisition of Shire, to settle some deep-seated concerns revolving around the potential market overlap with their blockbuster rival Entyvio. And Takeda, which took on a heavy debt load to buy Shire, clearly wanted the cash to pay down debt.