Update On New HCV Drug SPC3649

[Guest guest]

Update On New HCV Drug SPC3649

What Drug Are We Talking About ?

,SPC3649 is the name attached to a promising hepatitis C treatment that’s still in development.

When a drug is still in the early development its given a number. When the drug progresses successfully it is then given a name by the pharmaceutial company.

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Example: Vertex VX-950/now is referred to as Telaprevir.

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What Is So Promsing about SPC3649 ?

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Hepatitis C, like all viruses, has to hijack your cells to produce baby viruses. This makes them hard to treat-- you cant mess up a viruses life cycle without messing up a normal cellular process.

...Scientists noticed a host cell microRNA, miR-122, was super up-regulated in HCV infected cells. Apparently, HCV needs miR-122 in order to reproduce. So, if we could 'mess up' miR-122, we could mess up HCV infection.

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Aaaand it doesnt look like HCV was evolving resistance to the treatment (its an RNA virus guys, QUASISPECIES!)! ( From scienceblogs.com).

This drug will attack the virus indirectly by sequestering a host factor that the virus uses for its replication. It works by binding to and sequestering an endogenous microRNA called microRNA-122 that is specifically expressed in the liver and which the virus uses for its replicative cycle. And sequestering this basically removes it from the virus and hence stops the virus replicating. (From Audio Interview below)

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.."These studies show no evidence of viral escape, indicating that there will be fewer cases of relapse and non-responders. Viral “escape†or rebound refers to HCV genetic mutation, since the virus has a knack of transforming itself to escape treatment. " ( See Article Below)

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The Side Effect

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We always get excited about any new potential therapy, but we really get excited about one that has a great side effect. What is that side effect you ask ? It lowers 25 to 54% cholesterol levels, wait, thats *BAD cholesterol levels.

First the drug was tested in mice, then they moved to Africa green monkeys and onto primates.

mTherapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection

More on this drug from : hepc.bull 01-2010.

There are some issues of drug resistance that develop when some of these protease and polymerase inhibitors are used..Some side effects presently end the treatmentfor about 14% of participants. Early reporting suggests that this may not be so with this recently announced drug.

The compound in question is called SPC3649. The only side effect noted so far isa cholesterol lowering effect. It has produceda 350-fold reduction in HCV levels lasting for two months following 12 weeks of treatment. There was an additional advantage discovered, as the drug appears to reset the immune system in non-responders. Since there is a genetic disposition involved, some people have their immune system shut down rather than fight off the virus when they start interferon. It appears that this new drug“actually reset a number of interferon respondinggenes… that were deregulated atthe onset of treatment,†according to Santaris Pharma scientist Henrik Orum. “These genes are normalized… suggesting that the gene in non responders could be reset… [to responder levels].â€

These studies show no evidence of viral escape, indicating that there will be fewer cases of relapse and non-responders. Viral “escape†or rebound refers to HCV genetic mutation, since the virus has a knack of transforming itself to escape treatment.

Incidentally, this response could be followed by a jump of ALT during treatment,which might indicate viral breakthrough. This happens with interferon treatment and still happens with the use of the new complementary drugs nearing development in 10 to 15% of cases. This is a good reason to check your ALT regularly during treatment. They may be able to alter approaches at this point or consider treatment termination.The target of the SPC3649, microRNA122, that is required for HCV replication.

All of the six genotypes and over fifty subtypes of HCV are ‘addicted’ to microRNA122. The compound likely binds to it making it unavailable to HCV. Since microRNA122 is universal in many living organisms it is possible that the drug will work for everyone. “This paper adds to the growing body of evidence,†says Orum, “that the inhibitor platform has the potential to transform the field of RNA targeted therapeutics making specific silencing of RNA targets involved in disease a reality in human medicine in the longer run.†Other recent developments with this technology may have significant impacts on treatments for HIV, inflammatory disease and even cancer. It demonstrates a real potential forHCV treatment in a cocktail with the other inhibitors without the need for interferon.

hepc.bull -January 2010

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Is It Being Studied In Humans Yet ?.

The drug is in phase 1 clinical trials, they should be beginning phase 2 trials sometime next year.

..Second Phase 1 Study

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SPC3649 Multiple Dose Study in Healthy VolunteersOverview:Status: RecruitingStudy

State Date: September 2009Primary

Completion Date: Anticipated August 2010

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety StudyPhase: Phase 1

http://www.clinicaltrialssearch.org/spc3649-multiple-dose-study-in-healthy-volunteers-nct00979927.html

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About The Ressults

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May 1 2010

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BOSTON — Santaris Pharma is close to completing a second phase I study of its microRNA-targeting hepatitis C therapy SPC 3649, and expects to move the drug into phase II development later this year, a company official told RNAi News.

,The official, CSO Henrik Orum, also said Santaris has dropped its near-term plan to seek a partner for the therapy, which it will instead carry on its own at least through the first phase II trial in HCV-infected patients

mSPC3649 targets miR-122, the most abundantly expressed miRNA in the liver and one linked to cholesterol regulation and lipid metabolism. It is based on Santaris' locked nucleic acid technology, which comprises nucleic acid analogs in which the ribose ring is locked by a methylene bridge connecting the 2'-O atom with the 4'-O atom.

,In mid-2008, Santaris moved the drug into a phase I study, making it the first to test a miRNA-targeting drug in man. According to Orum, that single ascending dose trial enrolled 64 healthy volunteers and initially examined doses of the drug up to 6.4 mg/kg.

,"With the initial top dose of 6.4 [mg/kg], we didn't see anything in terms of the safety issues," he said. As such, the company amended the trial to include 9 and 12 mg/kg doses.In addition to observing no significant adverse events associated with SPC3649, Santaris saw evidence of a pharmacological effect as measured by reductions in serum cholesterol — a biomarker for miR-122, Orum explained this week during a presentation at the IBC Life Sciences' Oligonucleotide Therapeutics Discovery conference held here.

,Second Phase 1 Study

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The company also initiated a second phase I study, this time examining multiple ascending doses of the drug, which it expects to wrap up shortly, he said.Because data from this trial have not been publicly disclosed, Orum declined to comment on them. He did say, however, that Santaris is "happy with the results" and that the company is slated to begin a phase II study in HCV-infected patients "later this year."

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Phase 11 Study,

Both phase I studies were conducted in Denmark. He noted that the company is considering in which countries it will run the phase II trial.

,Meanwhile, Santaris has made the decision to keep SPC3649 in-house after partner GlaxoKline opted against licensing the drug.

,In late 2007, the companies inked a deal to develop and commercialize antiviral drugs based on the LNA technology (RNAi News 12/20/2007). As part of that arrangement, GlaxoKline had the option to in-license SPC3649.

,But as reported by RNAi News, GlaxoKline let that option expire (RNAi News 12/3/2009), leaving Santaris free to host licensing negotiations with other interested parties.Notably, GlaxoKline later said it had partnered with rival miRNA drug firm Regulus Therapeutics on a miR-122-targeting drug for indications including HCV (RNAi News 2/25/2010).

,This week, however, Orum said that despite "considerable interest … [in SPC3649] we've elected to keep it as a Santaris asset until we have conducted the first trials in patients with HCV. We think there is significant value creation in that phase, and we'd obviously like to retain that within Santaris … we have patient data."

Santaris Sues Mirrx Founder Over Blockmir Technology

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May 06

In his defense, Mirrx's founder charged that Santaris is aiming to gain control of the Blockmir technology as an alternative to the LNA technology used in its phase I HCV drug SPC3649, which he alleges falls under intellectual property controlled by Regulus Therapeutics.

Audio From J & F Blog 2009 expaining how SPC3649 will work

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abstract

Santaris Pharma http://www.santaris.com/NewsReleases/new-data-show-breakthrough-microrna-targeted-therapy-developed-using-santaris-pharma-a-s-proprietary-lna-technology-holds-promise-as-new-treatment-for/Default.aspx

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http://scienceblogs.com/erv/2009/12/new_hepatitis_c_treatment_with.php

http://Hepatitis Cnewdrugs.blogspot.com/2010/05/update-on-new-hcv-drug-spc3649.html