Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts from the ‘Rheumatology’ category

Juvenile rheumatoid arthritis (JRA) is a disease that results in chronic joint inflammation, and is the most common rheumatology disease in children.

The American College of Rheumatology classifies juvenile RA into 3 subtypes, one of which is systemic JRA.  The news that the FDA just approved tocilizumab (Actemra®) from Roche for pediatric systemic JRA (SJRA) is therefore good news for several reasons:

1. Very few drug companies obtain pediatric indications for their drug since registration trials are more routinely undertaken with adult patients.

2. In several adult phase III clinical trials, tocilizumab was also shown to delay joint damage as measured by ACR20, ACR50 and ACR70 responses.  An ACR 20 response requires a patient to have a 20% reduction in the number of swollen and tender joints.

If you look at the adult phase III clinical data that has been published for the AMBITION, LITHE, OPTION, TOWARD, RADIATE studies, what is noticeable to me is the high percentage of patients across the studies who had an ACR20 response within 24 weeks (70%, 56%, 59%, 61%, 50%); in all cases a significant improvement over placebo plus methatraxate or other disease modifying anti-arthritic drug (DMARD).

Source: Roche data on adult phase III trial results

However, it’s clear from the above data that fewer patients had deep responses e.g. ACR50, ACR70.  Tocilizumab is a treatment option for those who have failed previous RA therapies, and while not a cure, can provide symptom relief and improve joint function in those suffering from moderate to severe RA.

According to the Roche press release, data from the pediatric study known as TENDER, showed that 64/75 children (85%) of children with SJRA experienced an ACR30 improvement.  Given the fact the drug is already approved for adult use, and has extensive phase III trial data, a small pediatric sample size is not unexpected.


A pediatric approval is good news, as all too often pharma and biotech companies neglect this market.  I plan to write more in future posts about RA drugs in development as I think this is a market that may continue to evolve new treatment options over the next few years.

The December 17, 2010 issue of “Science” has the catchy of title of “Insights of the Decade”, one of which is an article by Jennifer Couzin-Frankel, “Inflammation Bares a Dark Side”, that describes the ubiquitous role of inflammation. She concludes that:

“Mediating inflammation in chronic diseases is a new frontier, its success is still uncertain.”

Inflammation has been shown to play an important role in multiple chronic illnesses such as cancer, and in type 2 diabetes it promotes insulin resistance and the death of pancreatic beta cells.  In 2007, Marc Donath and colleagues published a landmark study in the New England Journal of Medicine where he used the drug anakinra, in patients with type 2 diabetes, to block interleukin-1 (IL-1), a cytokine that mediates the inflammatory response. The conclusion of the paper was that:

“The blockade of interleukin-1 with anakinra improved glycemia and beta-cell secretory function and reduced markers of systemic inflammation.”

The finding that diabetes patients whose inflammatory response was blocked did better, has led several companies to work on drug development in this area.

One of these is the biotechnology company, Xoma, whose stocked jumped 200% in the week before Christmas.  Although there was no press release or announcement of any company news, it looks like investors decided to take a gamble that the phase 2 trial results for Xoma 052 in type 2 diabetes will be positive.  As often happens, the wisdom of the crowd, led to others joining the share buying frenzy.

Source: Google Finance. Xoma had previously announced on November 4, 2010 (emphasis added) that:

Enrollment completed in Phase 2a trial of XOMA 052 in patients with Type 2 diabetes:

This randomized, placebo-controlled trial, in which 74 patients were enrolled, is designed to evaluate extended biologic activity and safety of XOMA 052. Outcomes will include diabetes measures such as hemoglobin A1c, or HbA1c, and fasting blood glucose, or FBG, and C-reactive protein, or hsCRP, a biomarker of inflammation associated with cardiovascular risk. Interim results from the first three months of treatment in this six month trial are expected to be announced in the first half of January 2011.

Enrollment completed in Phase 2b trial of XOMA 052 in patients with Type 2 diabetes: This randomized, placebo-controlled dose-ranging trial enrolled 420 patients and is designed to further evaluate the safety and efficacy of XOMA 052 dosed once monthly compared to placebo. The results will include data on measurements of HbA1c, FBG and hsCRP. Top line results are expected to be announced in the first quarter of 2011.

Xoma 052 is a high affinity monoclonal antibody that targets the inhibition of IL-1 beta.  Its ultra-high affinity allows for monthly dosing and lower dose levels which supports patient compliance in chronic diseases. Positive phase 2 results for Xoma 052 in Behcet’s Uveitis was presented in November to the American College of Rheumatology.

According to the November 2010 Xoma Corporate Presentation, the overall market size for diabetes is $22B, of which the IL-1 share is $7B, raising the possibility that Xoma 052 could be a blockbuster if shown to be safe and effective.

Source: Xoma November 2010 Corporate Presentation

Looking at the above, perhaps the rush to buy Xoma stock before the holidays, was perhaps not as much of a gamble as one might think. Xoma 052 is certainly a product to watch this year.

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