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.

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

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UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

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Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

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UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

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Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.

As dis­as­ter struck, Ab­b­Vie’s Rick Gon­za­lez swooped in on Al­ler­gan with an of­fer Brent Saun­ders couldn’t say no to

Early March was a no good, awful, terrible time for Allergan CEO Brent Saunders. His big lead drug had imploded in a Phase III disaster and activists were after his hide — or at least his chairman’s title — as the stock price continued a steady droop that had eviscerated share value for investors.

But it was a perfect time for AbbVie CEO Rick Gonzalez to pick up the phone and ask Saunders if he’d like to consider a “strategic” deal.

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As­traZeneca's jug­ger­naut PARP play­er Lyn­parza scoops up an­oth­er dom­i­nant win in PhI­II as the FDA adds a 'break­through' for Calquence

AstraZeneca’s oncology R&D group under José Baselga keeps churning out hits.

Wednesday morning the pharma giant and their partners at Merck parted the curtains on a successful readout for their Phase III PAOLA-1 study, demonstrating statistically significant improvement in progression-free survival for women with ovarian cancer in a first-line maintenance setting who added their PARP Lynparza to Avastin. This is their second late-stage success in ovarian cancer, which will help stave off rivals like GSK.

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ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.