This piece from inPharma.com talks about Zyflo in lay terms and mentions Abbott's sales:
>>13/01/2004 - An ageing drug for asthma marketed by Abbott Laboratories could get a new lease of life from a revamp using drug delivery technology developed by SkyePharma of the UK.
Abbott sells the drug, called zileuton, in an oral formulation called Zyflo Filmtab that requires four times daily dosing. A small US company called Critical Therapeutics has now licensed rights to use zileuton in a new formulation developed by SkyePharma that will reduce the dosing rate and make it a more attractive treatment option for patients.
Zileuton was first introduced in 1997 as one of the first alternatives to steroids in asthma. Despite its early promise, the drug was held back by its onerous dosing regimen that reduced patient compliance with therapy and, in turn, asthma control. The drug was also associated with liver toxicity which meant that patients taking it required monitoring
Meanwhile, Zyflo soon lost out to rival products with similar but more selective mechanisms of action. It inhibits the inflammation that underlies asthma by inhibiting an enzyme, 5-lipoxygenase, that produces inflammatory mediators called leukotrienes. At around the same time, selective inhibitors of leukotriene receptors from Merck & Co (Singulair; montelukast) and AstraZeneca (Accolate; zafirlukast) were also launched, and Zyflo’s position as the first steroid-sparing drug for asthma was effectively undermined.
Singulair and Accolate won the marketing battle with their once-daily dosing and cleaner side effect profile – both eventually turning topping $1 billion in annual sales.
Critical Therapeutics believes it can tackle at least the dosing issue with the SkyePharma formulation, and there is also a possibility that a controlled-release formulation could also alleviate some of the liver toxicity seen with the original compound. But even if this is not the case zileuton could see a new lease of life in the new formulation.
Abbott does not record the sales of Zyflo, but they are thought to be a few tens of million dollars a year – small change for a company ranked 12 in the pharma industry with sales of nearly $10 billion in 2002, but a significant product for Critical Therapeutics.
The US biotechnology company has no therapeutics on the market at present, and an improved version of zileuton could top up its coffers while it develops the novel drugs in its pipeline, as well as bringing in a useful new royalty stream for SkyePharma.
And there is a chance that Zyflo itself – which Abbott is not including as part of the deal – could see something of a renaissance. Abbott has an ongoing collaboration with French genomics company Genset to identify ways of identifying the 4 per cent of patients prone to develop liver side effects with the drug before they start treatment. <<
inpharma.com
Snip from August 4th quarterly re pipeline:
>>The development status and milestones for each of the Company's product candidates are as follows:
Zyflo® Filmtab®, the tablet formulation of zileuton - Zyflo® Filmtab® is approved for marketing by the U.S. Food and Drug Administration (FDA). The Company is currently transferring technology to third-party manufacturers. Following successful scale-up and stability testing, a supplemental New Drug Application (NDA) will be submitted for the new manufacturing sites. Commercial launch of the product for the asthma market is planned for mid-2005. In addition, the Company has development efforts underway for additional indications including chronic obstructive pulmonary disease (COPD) and acne.
Zileuton, controlled-release formulation (Phase III) - Two pivotal Phase III clinical trials have been previously completed. Following technology transfer of manufacturing and formulation, a bioequivalence study in healthy volunteers is planned comparing the Company's controlled-release formulation to Zyflo® Filmtab®. The Company plans to submit an NDA in late 2005 for this twice-daily formulation.
Zileuton, intravenous (IV) formulation (Research) - Evaluation of several drug-delivery technologies is ongoing to develop an IV formulation designed to treat acute exacerbations of asthma, for which there are over two million hospital visits per year. A Phase I clinical trial is planned for 2005.
CTI-01 (Phase I) - The Company recently initiated its second Phase I trial in 60 healthy subjects following submission of an IND to the FDA in June 2004. A Phase II trial of the anti-inflammatory drug candidate is planned for the end of 2004 in patients who are at high risk for post-surgical complications following cardiopulmonary bypass.
HMGB1 Program (Pre-clinical) - In collaboration with development partner MedImmune, Inc., the joint development team has begun pre-clinical testing of fully human antibodies targeting HMGB1, a newly discovered cytokine identified as a potential late mediator of inflammation-induced tissue damage. Joint development efforts are focused on both chronic and acute indications in parallel. A clinical candidate is expected to be identified in early 2005.
Cholinergic Anti-inflammatory Program (Research) - The Company is in late-stage discussions with an academic center to in-license intellectual property, including composition of matter, for a family of known agonists targeting the nicotinic a-7 cholinergic receptor on the macrophage cell. This receptor has recently been shown to be integral in inhibiting the release of cytokines implicated in a range of severe acute inflammatory diseases that can result in multi-organ failure, and in chronic conditions such as rheumatoid arthritis. Execution of this agreement should accelerate development timelines in order to select a small molecule clinical candidate as early as 2005. <<
So it seems they are still on track with the timelines noted in the S-1. But is twice daily formulation going to be sufficient improvement to boost sales? COPD and acne?
The CR formulation seems to have yielded some improvement, safety-wise, too, but I'll save the details for the next post.
Cheers, Tuck |
