Thursday, March 14, 2013

Over 90% Viral Knockdown in HBV-Infected Chimpanzee with DPC Delivery


Arrowhead Research today provided a little appetizer ahead of its analyst event for ARC520, its candidate for the treatment of chronic hepatitis B (profiled here).  The press release stated that with a single injection of the DPC formulation, serum HBV DNA levels in a chronically infected chimpanzee were reduced by ‘greater than 90%’.  This suggests that the knockdown of the direct target, HBV mRNAs (incl. for the critical HBsAg), was on the same order.  Although the knockdown number here refers to a replicating virus, they are consistent with the high potency of DPC seen in other monkey studies.

The obvious limitation of the present study is that only one animal was treated.  Infected chimpanzee studies are almost impossible to conduct these days, and I am curious how the company got access to the animal in the first place.  The study is being conducted at the Texas Biomedical Research Institute and was led by Robert Lanford.  Dr. Lanford is well known for his chimpanzee work for viral infections, including proof-of-concept for miR-122 inhibition for the treatment ofHepatitis C (Santaris program) and, more recently, chronic HBV studies for Gilead’sTLR7-agonist GS-9620.

Nevertheless, as the animal served as its own control and HBV DNA levels do not fluctuate much from day-to-day, obtaining a credible >90% knockdown without being able to rely on a proper dose-finding study, is remarkable and suggests that more potent results would have been obtained with higher and more frequent dosing.

More about the clinical dosing plans and additional data on the chimpanzee, esp. the HBsAg knockdown data that are so critical to the immune reconstitution hypothesis central to ARC520 (read here for why), should be forthcoming at the March 25 analyst meeting.  Mark your calendars.

13 comments:

tufulipo said...

Does the chimp give us a clue who is interested in partnering the HepB program?

Anonymous said...

"Does the chimp give us a clue who is interested in partnering the HepB program"

Gee dude what a question inst it obvious "Cirque Du Solei" They are even prepared to consent to testing on all the animals. Dirk you are losing credibility a lot faster than you think my friend . Take your head out of the sand !!! " BUDA"
Oh and dont you ever try and come back down under ever again cus i will end up kissing you to death !!!

tufulipo said...

Hell hath no fury like a jilted Director of Business Development...

Anonymous said...

Dirk,

Is Benitec still working with Calando on Benitec's Hep C program? I know that Nucleonics at one time worked with Novosom on their Hep B and C program. Could Marina's SMARTICLES help Benitec's Hep C program? I would like to see all of these RNAi companies work together to create novel drugs that they could not create by themselves.

Dirk Haussecker said...

Non-viral delivery is not going to work for HepB or C ddRNAi. Only AAV at the moment stands a chance.

Dirk Haussecker said...

I should add though that your concept of RNAi companies sharing technologies is an important one.

Anonymous said...

If only you and I could have a direct line to the CEOs of the leading RNAi companies. I know it could never happen, but could you imagine the potential of a company that had all the IP and projects owned by Tekmira, Arrowhead, Benitec, Marina Biotech, Silence Therapeutics, and Rosetta Genomics( for the miRNA targets)? The CEOs would never agree to merge all these companies but if they cooperate and share technogies to create novel solutions, they can operate like an "RNAi Monopoly". Make Big Pharma pay up and grow their market caps to the tens of billions! I know, but we can dream right?

Anonymous said...

Dirk,

You should think of all the creative ways RNAi companies can work together and combine their best technologies to create novel drugs with unrivaled potency and safety. Then consult with them and get those drugs into trials and make us rich in the process!

Anonymous said...

Not a silly suggestion.

It's a big, rare opportunity to create a one stop, category owning, game changing shop.

It won't remain once the Co's start to commercialise.

Anonymous said...

It would be like Standard Oil monopolizing the oil industry in the 1800s! An RNAi monopoly with the best technologies in one company would have enormous power and we could own it now for pennies!

Anonymous said...

Would be something to see the flushes of sheer panic sweep over big pharma as this high potential high risk technology, capable of taking much of their market and more, vanishes back into the woods.

An eerie silence descends on camp big pharma..

'sshh!! what was that..? will it come back and eat us?'

Anonymous said...

re: twitter feed, gene therapy cure for HCV. would it be hard to justify to those for whom the oral regimes don't work?

Also once proved up safe and thus approved by FDA, would there be a market segment of patients who would prefer 1 shot injection, than 3 month daily oral regime, even if the oral regime worked?

what would we be talking, in percentages, that TT-034 could capture?

Dirk Haussecker said...

HCV treatments are becoming shorter, and without interferons, treatment duration is also becoming less of an issue to start with. The market that is left is really the non-responders, and even the non-responders might hold off on ddRNAi treatment if they see promising alternatives on horizon (lots in the pipeline). Having said that there should still be a small patient population left so ddRNAi can prove itself, but because so much of the future treatment landscape is uncertain, how Benitec wants to navigate development will be interesting/a challenge.

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