Pharma: January 2012 Archives
At last, something positive (albeit very preliminary) to report about the use of human embryonic stem cells (hESCs)...in disease, no less.Yesterday The Lancet published (and made freely available—!) early safety results from Advanced Cell Technology's 2 prospective phase 1/2 clinical studies of hESC-derived retinal pigment epithelium in 2 blind patients, one with dry age-related macular degeneration and the other with a much rarer, genetic equivalent, Stargardt's disease. Both diseases result from the degeneration of the RPE, which leads to photoreceptor loss, and the former condition is the leading cause of blindness in the developed world.*
During the 4 months after subretinal transplantation of RPE cells, the investigators confirmed structural attachment and no evidence of hyperproliferation, other signs of abnormal growth, or rejection in either patient. In addition, the patients reported very modest improvements in vision from baseline; although a placebo effect in these cases is probably very strong. Most important, however, is that neither patient described a deterioration in vision.
The authors conclude that the "future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue." The estimated enrollment for each of the ongoing studies is 12.
The share price of ACT's penny stock has risen considerably since early January, from 7 cents to 18 cents (a 150% jump), and the rise began weeks before the publication of yesterday's cautiously favorable article—a phenomenon that suggests some insider knowledge or buzz. On January 5th, the company announced that its chairman and CEO, Gary Rabin, would be presenting at the EBD Group's Biotech Showcase, and specifically at the Regenerative Medicine State of the Industry Briefing workshop on January 10th. Reason suggests that Rabin mentioned something concrete at the workshop to maintain an already growing interest in ACT.
* For leading causes of blindness in the world, go here.Graphic of retina with evidence of AMD from an NIH web page.
01/25/12 addendum: According to an astute ophthalmologist, it should be noted that patients in these hESC transplantation studies require immunosuppression to reduce the risk of graft rejection, namely in the form of tacrolimus (eg, Prograf) and mycophenylate mofetil (eg, CellCept). Although it's been previously reported that hESC transplantation may be more feasible in the eye, because the environment is relatively immune privileged, this is only really true for the cornea and natural lens of the eye, which lack blood vessels. The retina and the underlying choroid are highly vascular; consequently immunosuppression is a must with the subretinal grafting of hESC RPE cells. Autologous retinal grafts (which appear to be in an even earlier stage of development) would preclude the need for immunosuppressants. This recent review describes the current status of using stem cells for the treatment of retinal diseases.
Medivation and partner Pfizer will cease development of Dimebon (latrepirdine), a now thoroughly defunct antihistamine, "for all indications and will terminate the ongoing open label extension study in Alzheimer's disease." The small biopharm company announced the official end of Dimebon development yesterday in a press release, and the story was picked up by the WSJ. Dimebon's demise is based on flat results in the companies' CONCERT trial, a phase 3 study in which Dimebon was assessed as add-on treatment to symptomatic treatment donepezil (Aricept) in patients with mild-moderate AD.Previous news on Dimebon (March 2010) was that it failed to improve cognition or global functioning in a placebo-controlled phase 3 study of patients with AD, and Medivation's share price plummeted 30 points on the dated news. In 2008, Pfizer agreed to pay Medivation $225 million upfront and another $500 million when Dimebon was FDA approved. The agreement—which split development costs and potential profits on a 60-40 basis (Pfizer assumed the larger share)—also conferred licensing rights to Pfizer for use of the drug in Huntington's disease. But Dimebon also disappointed in this devastating condition.
Pfizer was evidently betting on the chance that Dimebon would sail through US clinical development, given very favorable phase 2 results published in The Lancet in July of 2008. In a randomized, double-blind, placebo-controlled, multicenter study (N = 183) that was conducted entirely within Russia and funded by Medivation, patients with mild-moderate AD who received Dimebon demonstrated significantly less cognitive decline at 6 months, as measured by the ADAS-cog (mean score difference, 4.0; P < .0001). Although some were scratching their heads as to why an antihistamine would have a disease-delaying or merely symptomatic effect in AD. The ultimate, tired lesson: promising phase 2 results are not a harbinger of anything, except chancy phase 3 study.
Medivation reminds us that it's also developing an investigational drug (MDV3100) with Astellas for the treatment of advanced prostate cancer. The compound is in the phase 3 stage, and Medivation got a huge bump in its stock price in late October just before news of very favorable survival data was publicly released.
