Isis and GSK announce plan to initiate Phase II/III TTR amyloidosis study
Nov 09, 2012 (Datamonitor via COMTEX) -- Isis Pharmaceuticals, Inc., an antisense technology company, and GlaxoSmithKline, or GSK, have announced the development plan to initiate a Phase II/III clinical study with ISIS-TTRRx.
Both companies have agreed to amend the clinical development plan and financial terms relating to ISIS-TTRRx to reflect the accelerated development plan for the drug.
The revised development plan anticipates initiation of a Phase II/III, registration-directed, clinical study later in 2012. ISIS-TTRRx is one of several drugs in Isis' pipeline that Isis expects will begin registration-directed studies within the next several years.
ISIS-TTRRx is an antisense drug in development with GSK for the treatment of TTR amyloidosis, a severe and rare genetic disease characterized by progressive dysfunction of peripheral nerves and/or heart tissue.
Under the terms of the original collaboration agreement with GSK, which includes five programs in addition to the TTR program, Isis is eligible to receive on average up to $20 million in milestone payments per program, before Phase II proof-of-concept, plus a licensing fee, additional post-licensing milestone payments and double-digit royalties on sales from each product.
Isis has already received $10 million in milestone payments from GSK related to the development of ISIS-TTRRx. Under the amended terms of the agreement Isis will receive a $2.5 million upfront payment and is eligible to earn a $7.5 million milestone payment upon the initiation of the ISIS-TTRRx Phase II/III study.
Isis is also eligible to earn an additional $50 million in pre-licensing milestone payments to support the ISIS-TTRRx Phase II/III study. In addition, GSK has increased the regulatory and sales milestones payable to Isis should the product achieve registration and meet certain sales thresholds. Isis will also receive double-digit royalties on sales of ISIS-TTRRx.
"In our Phase I study, we demonstrated that ISIS-TTRRx was generally well tolerated and produced dose-dependent significant reductions in TTR protein with several subjects reaching TTR protein levels that were below the limit of assay detection," said Brett Monia, senior vice president, antisense drug discovery at Isis. "We anticipate initiating the next clinical study this year, which will evaluate the effects of ISIS-TTRRx on neurological dysfunction and on quality-of-life in patients with familial amyloid polyneuropathy."
"We have a robust pipeline of novel new drugs. Many of which, including ISIS-TTRRx, could advance into registration studies in the next 12 to 18 months. Together with GSK, we have been able to rapidly advance the TTR program from research to late-stage clinical development in just over two years," said Lynne Parshall, COO and CFO at Isis. "Under the updated plan, Isis continues to manage the clinical development of ISIS-TTRRx while benefiting from GSK's late-stage development and commercial expertise. We believe that ISIS-TTRRx could be a best-in-class medicine for patients who have limited therapeutic options."
"Together with GSK, we have been able to rapidly advance the TTR program from research to late-stage clinical development in just over two years,"
I think a plattform technology like Isis antisense technology which is able to advance drugs like the TTR or SMN programs from research to late -stage clinical development in 2-3 years is not really worthless.
The next severe and rare diseases drugs in the pipeline are myotonic dystrophy type 1 or DM1 and Huntington's disease both with a very rapid path of development.
"In just a few years, we’ve been able to expand our severe and rare disease franchise and maintain a broad research program in which we’re evaluating many different diseases that could be treated with an antisense drug.
Of these diseases, myotonic dystrophy type 1 or DM1 is characterized by progressive muscle atrophy, weakness and disabling muscle spasms. Currently there are no treatments available for patients with DM1 even through these diseases expect to affect more than 150,000 patients in the U.S., Europe and Japan combined. DM1 is caused by toxic RNA, not a protein making it very difficult to treat using standard drug discovery technologies such as small molecule. Because the antisense technology targets RNAs, we have a unique opportunity to develop an effective drug for these patients.
Our new collaboration with Biogen Idec to develop an antisense drug to treat DM1 is structured similarly to our earlier collaboration with Biogen Idec for our SMA drug, albeit for a much earlier program. We’ve provided Biogen Idec with an option to license in the future an antisense drug to treat DM1."
"So, it’s obvious that using our drug discovery technology, we can develop antisense drugs to many different severe rare diseases and we have an active research program doing just that. As an example, there are now two very striking papers that have recently been published that demonstrate the potential of antisense drug to treat these hard-to-treat disease. Earlier in the summer we and our collaborators, UCSD and Genzyme published a paper in the journal Neuron that highlights the selectivity and potential benefit of the management’s approach to the treatment of Huntington's disease.
We have reported that a single injection of Antisense drug designed to target Huntington RNA produced a rapid sustained improvement in a mouse model of Huntington's disease. After one injection directly into the spinal fluid treated mice exhibited increased mobility and steadily progressed in normal mobility.
These improvements were still being observed nine months after a single dose was administered. I am very encouraged with this work and the clear demonstration of activity in an animal model of Huntington's disease and we look forward to advancing this program into development in the near future.
More recently, we and our collaborators at the University of Rochester published paper in the journal Nature that demonstrated similar striking sustained results in a mouse model of myotonic dystrophy. In this study we were able to rapidly reduced our target of toxic RNA in scalable muscle and reduce the disease for more than year after treatment. These data are especially significant as this is the first time we have developed an antisense drug to target toxic RNA and this is the first time we published data showing the potential for therapeutic benefit by targeting an RNA and scalable muscle. We used to think that second generation antisense drugs did not work well in scalable muscle, but thanks to continued advances in our technology and our understanding of the mechanisms by which antisense drug distributed in the body. We now know that we can get our antisense drug into muscle cells with very good effects.
By the way I’ve emphasized that the drugs are formulated in simple saline solution, doesn’t require any special formulation for any disease. This of course expands the potential utility even in antisense once again. As Lynne mentioned we recently patterned our myotonic dystrophy program with Biogen Idec and together we’re moving this program forward rapidly to identify development,"