Biotech Strategy Blog

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

Posts tagged ‘Diabetes’

I’m off to a conference in Orlando today, so thought it might be interesting to follow-up on my previous post about the emerging medical device/biotechnology cluster around Austin, Texas to think about what’s happening in Central Florida.

Orlando is most well-known for Disney and theme parks, and major conferences (see my post on attending the ASH annual meeting in Orlando last year). However, the opening of a new medical school, children’s hospital and medical research institute will undoubtedly lead to biotechnology and biomedical companies considering start-ups in the surrounding area.

Florida, like Texas, offers no personal taxation and Orlando is also well connected for flight connections throughout the country.

Orlando, in my opinion, is further behind Austin, and to some degree all cities with a medical school, in it’s attempt to drive research and innovation.  Whether Central Florida can establish a critical mass of companies and sufficient industry talent is the challenge, especially as multiple regions across the United States are also competing for biotechnology $.

However, even if Orlando does not become a major biotechnology cluster, it is more likely to become a major center for clinical and biomedical research.

In April 2009, the La Jolla based Sanford-Burnham Medical Research Institute opened a new research facility at Lake Nona in Orlando.  It is home to 900 scientists undertaking R&D on drug discovery, stem cells, nanomedicine and translational research.

One of research areas it is focusing on is diabetes and obesity, or diabesity as it is rapidly becoming known, an area that is rapidly reaching pandemic proportions in the United States. A symposium on Frontiers in Biomedical Science: Metabolic Networks and Disease Signatures will be held on March 11.

Luke Timmerman’s post on Xconomy about the Institute and the $50M gift it received last year to change its name is well worth a read.  In another post, he also raises the question of whether biotechnology companies can make money going after diabesity, notwithstanding the market opportunity? Need and market opportunity don’t always translate into valid targets for drug development, especially when many of the issues to do with diabetes and obesity relate to lifestyle and food content.

The Sanford-Burnham Medical Research Institute is the cornerstone of a cluster of bio-medical research companies and healthcare institutions, including the M.D. Anderson Orlando Cancer Research Institute, the new University of Central Florida (UCF) College of Medicine that opened in 2009, and Nemours Children’s Hospital that will open in 2012.

I think it will take several years before we can see if a significant biotechnology cluster grows up around these research and medical institutions.  Whether Central Florida and Orlando can grow into a leading biotechnology region remains to be seen.

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 concluded 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 accrual was complete in the Phase 2a trial of XOMA 052 in subjects 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

Whether these numbers are realistic or ‘pie-in-the-sky’ dreams remains to be seen and we will have to wait and see what happens with future study readouts.

Note: Additional information on the deal with Servier can be found here.

Update March 18th 2014 by @maverickny

FDA awarded Xoma and Servier orphan drug designation for XOMA 052 (gevokizumab) for the treatment of pyoderma gangrenosum (PG), a rare disease that induces painful skin ulcers.  Standard therapy involving corticosteroids or cyclosporin are effective in approx. half of patients, but for those that relapse this new approach may offer new treatment options.

The two companies previously signed development and financial agreements including a 2011 agreement to commercialize XOMA 052, an anti-inflammatory drug candidate and another in 2013 to start the Proof-of-Concept (POC) clinical program to study gevokizumab.

Earlier this month, Xoma provided an update on its gevokizumab development program:

“Based on results from the Company’s Phase 2 program in patients with erosive osteoarthritis of the hand (EOA), XOMA does not intend to launch pivotal development for the broad EOA indication. The Company will conduct a review of the full dataset to determine if there is a segment of the patient population that best responds to gevokizumab therapy prior to initiating any potential additional clinical studies in this indication.”

The phase 3 program for gevokizumab in patients with pyoderma gangrenosum thus looks to be the best shot they have with this agent at present.

Update August 28th 2017 by @maverickny

Novartis have acquired the rights to Xoma’s gevokizumab following the phase 3 failure 18 months ago. The company is paying $31 million (€26 million) upfront for the distressed assets relating to the anti-IL-1 beta allosteric monoclonal antibody.

The company have previously garnered FDA approval for Ilaris in two subtypes of the rare auto-inflammatory diseases cryopyrin-associated periodic syndromes in 2009. A large trial in at-risk cardiovascular disease patients with high levels of chronic inflammation also began enrolling patients.

Data presented recently suggest Novartis has succeeded in demonstrating an anti-inflammatory drug can cut the risk of major cardiovascular events so if the company can make the commercial case for Ilaris, its big bet on cardiovascular disease may pay off. Where gevokizumab fits in with the anti-inflammatory portfolio isn’t yet clear.

Update January 7th 2019 by @maverickny

Things are becoming more interesting on the gevokizumab (now VPM087) front.

Novartis have just opened a phase 1 trial exploring the impact of adding gevokizumab to standard of care anti-cancer therapies for metastatic colorectal, gastroesophageal, and renal cancers with different arms for 1/2/3 line therapies.

Initial data are expected year end 2022, so it will be a while before we see what happens in terms of the study readout.

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Human eye cross-sectional view. Courtesy NIH N...Image via Wikipedia

VEGF Trap-Eye is a formulation of VEGF Trap (aflibercept) and is an anti-angiogenic agent that can be injected into the eye to stop the proliferation of blood vessels. Regeneron (REGN) are co-developing it with Bayer (BAY) and it is currently in clinical trials for the treatment of wet Age-Related Macular Degeneration (AMD), Diabetic Macular Edema (DME) and Central Retinal Vein Occlusion (CRVO).

Phase II DME clinical trial results presented at the
Angiogenesis 2010 meeting in Miami showed the primary endpoint of a
statistically significant increase in visual acuity over 24 weeks compared to
the standard of care (laser treatment) was met.

There are high levels of vascular endothelial growth factor (VEGF) associated with DME, so the news that VEGF Trap-Eye has biological activity in this disease is positive.What makes this data promising is the fact that DME is the leading cause of blindness in adults under 50 and there are 370,000 Americans with clinically significant DME with 95,000 new cases a year.

The ability to treat DME by an eye injection, rather than use an expensive laser will make it easier to treat the disease. It will be interesting to see what how the cost of treatment with VEGF Trap-Eye compares to laser therapy procedures, should the agent make it to market.

The recent pricing issue faced by Genentech with its VEGF inhibitors Lucentis
(eye indications) and Avastin (oncologic indications) are also relevant because
Regeneron are developing VEGF-Trap in cancer with it’s partner sanofi-aventis
(a client).

For VEGF Trap-Eye, Regeneron retains all U.S. marketing
rights, while Bayer has rights to market ex-US in return for a 50/50 profit
share with Regeneron.The results so far look promising and aflibercept looks like an interesting agent well worth watching as the development moves forward.

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