Genzyme Oral Pill for Gaucher’s Succeeds in Trial, Aims to Extend Key Revenue Stream

Genzyme (NASDAQ:GENZ) said this afternoon that its next-generation, oral drug for Gaucher disease passed a mid-stage clinical trial, providing a degree of assurance that the Cambridge, MA-based biotech powerhouse can sustain its franchise for treating the rare genetic disease.

The study, which included 26 patients, showed the oral drug was safe and effective. And the trial showed that the drug met its main goal in 91 percent of patients who took the drug over a year’s time. The results were presented today at the Lysosomal Disease Network World meeting in San Diego.

The trial represents an important test for the drug, although it will still have to clear another late-stage clinical trial expected to begin in mid-2009 before it can win FDA approval for sale in the U.S. This drug is strategically important to Genzyme. Imiglucerase (Cerezyme), the company’s current treatment for Gaucher, is its top-selling product that raked in $1.24 billion in 2008 sales, or more than a quarter of the firm’s total revenue of $4.6 billion. But two critical patents for the treatment expire in August 2010 and August 2013, according to regulatory filings.

“Given Cerezyme’s unique safety and efficacy profile, we set a high threshold for success, and the results were better than anticipated, indicating a potent, highly-specific and well-tolerated molecule,” said Geoff McDonough, a senior vice president with Genzyme, in a statement.

The oral Gaucher drug, tentatively called Genz-112638, would come with a longer patent life, and is also intended to be a more convenient option for people with Gaucher. About 10,000 patients worldwide have the disorder, and the current imiglucerase treatment is only available through intravenous injection.

The study of Genzymes’s oral Gaucher drug showed that the treatment decreased spleen and liver growth that is common among patients with the disease. The drug also proved effective in raising levels of hemoglobin, a protein that carries oxygen in the blood, and platelet cells, which help form clots, according to Genzyme. The study also showed lower levels of an antibody released in fatty tissues in patients who took the drug.

The company says that the there was a small number of patients who had mild adverse reactions to the drug early in the trial, but those adverse events did not require medical treatment. Of the 26 patients who enrolled in the trial, 22 completed the full year of treatment, and 20 chose to stick with the drug after the study ended, Genzyme says.

I have no clue how old this info is (the website says 1997), but it is worth looking into seeing how this panned out…

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In the past couple of years, attempts to treat Type 2 babies with Ceredase have been made in one case in America by Prof Gregory Grabowski, Director of Genetics, Children’s Hospital, Cincinatti, and in two cases in Italy by Dr Bruno Bembi at the Children’s Hospital, Trieste, but without success.

Work is also being carried out in America on a drug called L-cycloserine which is claimed to help Type 2 children. Experiments have taken place on ‘mice with Gauchers’ and the drug has been in use on humans suffering from other illnesses, such as tuberculosis, for some time. So far it has not been used on Type 2 babies but Dr Meir Lev, Director of Research Services and Development, City University of New York Medical School, believes it could be effective. This drug works by slowing down the accumulation of Gaucher cells in the body rather than supplementing the missing enzyme (which is what Ceredase does). The theory is by preventing new accumulation, any residual enzyme produced in the body will reduce or eventually eliminate the existing Gauchers cells.

Similar research is being carried out with a different substance called NB-DNJ by Dr Terry Butters and Dr Frances Platt at the Glycobiology Institute, University of Oxford. It is hoped that this or a similar substance will also inhibit the accumulation of Gauchers cells.

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More things to check out:
http://www.investmentguide.co.uk/gaucher/dec2007p13.pdf
http://www.investmentguide.co.uk/gaucher/contents.htm

http://www.cell.com/abstract/S0092-8674(08)01001-5

Tissue culture of immortal cell strains from diseased patients is an invaluable resource for medical research but is largely limited to tumor cell lines or transformed derivatives of native tissues. Here we describe the generation of induced pluripotent stem (iPS) cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance; these diseases include adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III, Duchenne (DMD) and Becker muscular dystrophy (BMD), Parkinson disease (PD), Huntington disease (HD), juvenile-onset, type 1 diabetes mellitus (JDM), Down syndrome (DS)/trisomy 21, and the carrier state of Lesch-Nyhan syndrome. Such disease-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation invitro, thereby enabling disease investigation and drug development.

I found this clinical trial on the NINDS (National Institute of Neurological Disorders and Stroke) website – Convection-Enhanced Delivery of Glucocerebrosidase to Treat Type 2 Gaucher Disease.

This single-patient study includes an 8-month-old male with Type 2 Gaucher disease with progressive neurological decline.  From what I can gather, they infused the missing glucocerebrosidase enzyme directly into his brain.  I know that Cerezyme doesn’t cross the blood-brain barrier, which is why Gaucher’s Disease Type 2 and Type 3 are ultimately fatal with neurologic degradation.

But I can’t find anywhere to see the results of the study or what happened?!  I would love to know what the results were!!  If anyone has any suggestions, please let me know.

Study Start Date:	October 2005
Estimated Study Completion Date:	November 2006

My non-science brain is trying to process all the information there is out there on Gaucher’s disease. 

In my research, I’ve come across quite a few recent articles regarding a link between Parkinsons and GD, even on the Michael J. Fox Foundation for Parkinson’s Research.  Google has over 125,000 documents listing both of those diseases in the same page.  (I know that doesn’t mean there are 125,000 pages on the two together, they could be just listed on the same page).  I definitely want to look more into this, as perhaps this is one of the missing pieces of one of the puzzles…

Understanding the Role of Glucocerebrosidase in Parkinson’s Disease Pathogenesis
Parkinson’s Disease and Gaucher’s disease share many clinical and neuropathological features.Treatment of Parkinson’s Disease with AT2101, a Compound that Increases the Activity of Endogenous Glucocerebrosidase
Genetic association studies have suggested a link between Parkinson’s and Gaucher disease. Gaucher disease is a lysosomal storage disorder caused by mutations in the gene GBA, which results in a loss of glucocerebrosidase (GCase) enzyme activity and a toxic accumulation of glucosylceramide in the lysosomes. Several studies have found an over-representation of GBA mutations among patient’s with Parkinson’s disease (up to 14 percent in non-Jewish populations and 30 percent in Ashkenazi Jews)…Together these models will provide a test of AT2101 efficacy for the reduction of alpha-synuclein in both Gaucher-associated and idiopathic Parkinson’s.

This gives me hope that Hannah may not have to have IV infusions (Cerezyme) when she is older for the physical symptoms of Gaucher’s Disease!  Being able to take a pill would be so much easier!!!!  Need to keep my eye on this one!  (Hopefully we don’t have to worry about neuro symptoms, but if we do, we have a lot more work to do!)

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Amicus Therapeutics Presents Positive Data from Phase 2 Clinical Trial of Plicera(TM) for Gaucher Disease

Amicus Therapeutics, a biopharmaceutical company developing small-molecule, orally administered pharmacological chaperones for the treatment of human genetic diseases, announced today that the Company will present positive results from a Phase 2 clinical study of Plicera(TM) (isofagomine tartrate) for Gaucher disease at the American College of Medical Genetics (ACMG) Annual Meeting from March 12-16 in Phoenix, AZ. Results from the fully enrolled Phase 2 trial support the previously reported interim findings that Plicera was generally safe and well tolerated at all doses and increased target enzyme activity levels in a majority of patients.

Phase 2 Plicera data presented at ACMG

The primary objective of this study was to evaluate safety and tolerability of different doses and dosing regimens of Plicera. The secondary objective was to evaluate certain pharmacodynamic measures of treatment, including effects on GCase (the enzyme deficient in individuals with Gaucher disease) levels in white blood cells.

Thirty patients with Gaucher disease (8 men and 22 women between the ages of 18 and 63) were enrolled, and there were 12 unique alleles represented including the most common N370S and L444P mutations. Patients were on enzyme replacement therapy (ERT) with imiglucerase for an average of 9 years prior to entering the trial, and they temporarily discontinued ERT to receive Plicera for the 4 week duration of the study.

    The key findings from the trial were as follows:

      -- Plicera was generally well-tolerated at all doses evaluated,
         and no serious adverse events were reported.
      -- GCase activity as measured in white blood cells was increased
         in 20 of the 26 patients with evaluable GCase data, and 5 of
         the 6 patients without a clear increase were either in the
         lowest dose cohort or the cohort dosed least frequently.
      -- As expected in this short term study, the levels of relevant
         markers of Gaucher disease including platelet counts,
         hemoglobin levels, glucocerebroside (substrate) levels,
         chitotriosidase activity and pulmonary activation-related
         chemokine (PARC) levels were maintained.

“These data give us great confidence in moving our Gaucher program forward,” said John F. Crowley, President and CEO of Amicus Therapeutics. “In addition to a 6-month Phase 2 study in individuals naive to ERT, which is currently underway, we plan to initiate a longer-term study in individuals switching from enzyme replacement therapy to Plicera in the second half of this year.”