Posted on December 9th, 2013
by Paul Ashton, Ph.D.
pSivida is evolving from a drug delivery company, out-licensing its technologies and products for others to develop and sell, to a Specialty Pharma model, where we develop and sell our own products.
The company’s lead product is Medidur for posterior uveitis, which is now in Phase III trials. Posterior uveitis affects approximately 175,000 people in the US and is difficult to treat. It’s the third largest cause of blindness in the US, and is responsible for 30,000 people being blind. We are very optimistic about Medidur for this disease. I’ll get into the details shortly.
We are also moving forward with our Tethadur sustained release technology, designed to provide local or systemic sustained release of Biologics (peptides, proteins and anti-bodies). Patents covering Biologics with combined annual sales of $50B-$80B/year are going to be expiring in the next 5-10 years. These patent expirations and the emerging BioSimilar/BioBetter space are going to create a huge appetite for life cycle management technologies; sustained release could offer a key to the next generation of Biologics. For example, in the eye space the two biggest products are now Biologics (Eylea and Lucentis), which need to be injected directly into the eye typically every six weeks indefinitely. A sustained release system that changed this to, say, once every six months would be a game changer.
We are continuing to look at collaborations and partnerships as part of our strategy even as we move to the Specialty Pharma model, and there several great reasons for doing so. First, collaborations give us leverage. We are talking about some very big markets. It is very difficult or a small company to go up against one of the Big Pharma players, no matter how good your technology. However if you are partnered with one of their big competitors, things can be quite different. Second, partnerships can help us achieve diversity, developing more products and in more therapeutic areas than would be possible (or advisable) under a “go it alone” strategy. And third, partnering — particularly for products one wouldn’t otherwise be developing — provides cash in the form of up-front fees, license fees and the rest, and this can subsidize the development of additional products more central to one’s strategy. For example, we have received over $30m so far from Alimera Sciences under our ILUVIEN collaboration even before any profit split on sales. We also retain the ability under our Alimera agreement to develop Medidur for uveitis and this work is to be subsidized by cash inflows from the DME application.
Now let’s get into reasons for our optimism about Medidur in posterior uveitis. Medidur is a sustained release micro-insert that delivers the same drug, fluocinolone acetonide, as the FDA approved Retisert (which we successfully developed with Bausch and Lomb). Retisert was approved by the FDA for uveitis affecting the posterior segment of the eye, the same indication we’ll be seeking for Medidur.
Retisert is surgically inserted into the back of the eye where it provides effective treatment of posterior uveitis for approximately 30 months. The Medidur micro-insert is injected into the eye in an office visit and releases the same drug for 36 months.
Bausch & Lomb conducted clinical trials on the device for both posterior uveitis and DME. Data from the uveitis clinical trials showed that Retisert is highly effective against uveitis (as measured by recurrence rates of the disease) and was also effective in treating DME, with 28% of patients gaining 15 letters of vision at two and three years. In the FAME trials in DME conducted by Alimera, the micro-insert had essentially the same efficacy at two and three years (approximately 30% of patients gaining 15 letters) so in DME at least Retisert and the micro-insert have the same efficacy. For both DME and uveitis the mechanism of the drug is the same, binding to glucocorticoid receptors. Beyond a certain point the system becomes saturated (or plateaus), so adding say twice as much drug does not significantly increase receptor binding. Therefore, in the plateau region the therapeutic effects of a drug are broadly the same regardless of dose. The clinical data from the Retisert and ILUVIEN trials indicate that both these devices achieve drug levels that are in the plateau region, their efficacy is very similar even though Retisert has 3 time more drug. We expect therefore that the drug levels achieved with the micro-insert will be therapeutic in posterior uveitis.
So we think we’ll have efficacy, the other half of the equation is safety. Retisert is FDA approved and is highly effective in uveitis but it does have some significant side effects. In both the uveitis trials and the DME trials Retisert showed elevated intraocular pressure (IOP) and cataract, side effects associated with the FA steroid. Approximately 60% of patients in both sets of Retisert trials developed IOP above 30 mmHg, and more than half of these (35% of the total) required surgery to reduce their IOP. In addition, almost all patients who had not previously had a cataract in treated eyes developed them. The important thing here is that for Retisert 1) the side effect profile was very similar in both DME and uveitis and 2) with these side effects the risk benefit profile was acceptable to the FDA in view of the seriousness of posterior uveitis. We expect therefore that the phase III trials of the micro-insert in uveitis will show similar side effects to those seem in the FAME DME studies (and far lower than Retisert). We would also anticipate that the risk benefit profile for the micro-insert in posterior uveitis will be even better than that the FDA approved Retisert. Recently preliminary results from an investigator sponsored study in posterior uveitis supported this hypothesis.
We met with the FDA toward the end of last year and they provided suggestions to our clinical protocol and clinical trial design which we incorporated into the Phase III study now underway.
As we move forward on our strategy of becoming a Specialty Pharma company our partnered programs will continue to be important to us as source of funding, a means to diversity and as a means to “polish” our technologies. Developing our own products, particularly low hanging fruit, such as the Medidur product for posterior uveitis, will increasingly move to center stage.
Forward Looking Statements
SAFE HARBOR STATEMENTS UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995: Various statements made in this blog are forward-looking, and are inherently subject to risks, uncertainties and potentially inaccurate assumptions. All statements that address activities, events or developments that we intend, expect or believe may occur in the future are forward-looking statements. The following are some of the factors that could cause actual results to differ materially from the anticipated results or other expectations expressed, anticipated or implied in our forward-looking statements: uncertainties with respect to: Alimera's ability to obtain regulatory approval for ILUVIEN for DME in the U.S. through the advisory committee or otherwise, and if approved, to finance, successfully commercialize and achieve market acceptance of, and generate revenues to pSivida from, ILUVIEN for DME in the U.S.; Alimera's ability to finance, achieve additional marketing approvals, successfully complete pricing and reimbursement discussions for, commercialize and achieve market acceptance of, and generate revenues to pSivida from, ILUVIEN for DME in the EU;; the ability to finance, complete and achieve a successful outcome for Phase III trials for, and file and achieve marketing approvals for, Medidur for posterior uveitis, including efficacy, side effects and risk/benefit profile, as well as uncertainty as to the ultimate results of the investigator-sponsored trial for Medidur for posterior uveitis; initiation, financing and success of Latanoprost Product Phase II trials and exercise by Pfizer of its option; ability to utilize Tethadur and BioSilicon to develop product candidates and products and potential related collaborations; initiation and completion of clinical trials and obtaining regulatory approval of product candidates; continued sales of Retisert; adverse side effects; ability to attain profitability; ability to obtain additional capital; further impairment of intangible assets; fluctuations in operating results; decline in royalty income; ability to, and to find partners to, develop and market products; termination of license agreements; competition and other developments affecting sales of products; market acceptance; protection of intellectual property and avoiding intellectual property infringement; retention of key personnel; product liability; consolidation in the pharmaceutical and biotechnology industries; compliance with environmental laws; manufacturing risks; risks and costs of international business operations; credit and financial market conditions; legislative or regulatory changes; volatility of stock price; possible dilution; absence of dividends; and other factors described in our filings with the SEC. Given these uncertainties, readers are cautioned not to place undue reliance on such forward-looking statements. Our forward-looking statements speak only as of the dates on which they are made. We do not undertake any obligation to publicly update or revise our forward-looking statements even if experience or future changes makes it clear that any projected results expressed or implied in such statements will not be realized.