Monday, June 17, 2019
Remoxy ER
Pain Therapeutics Announces Feedback from Recent Meeting With FDA on Remoxy
AUSTIN, Texas, Feb. 05, 2019 (GLOBE NEWSWIRE) -- Pain Therapeutics, Inc. (Nasdaq: PTIE), a clinical-stage drug development company, today announced feedback from a meeting held January 31, 2019 with the U.S. Food and Drug Administration (FDA) regarding the drug candidate, Remoxy ER. Remoxy is the trade name for a new type of abuse-deterrent, extended-release gel formulation of oxycodone (CII) with physical/chemical properties intended to deter abuse. As previously disclosed, we requested this meeting to resolve disagreement around comments and conclusions made by FDA in 2018 during a regulatory review of a New Drug Application (NDA) for Remoxy.
During this meeting, we learned that i) FDA denies making math errors, material mistakes or misrepresentations during a June 2018 Advisory Committee Meeting for Remoxy, despite clear evidence to the contrary; ii) comparator data is irrelevant for the evaluation of abuse-deterrent properties, despite FDA written guidance which explicitly states the opposite; and (ii) that we would need to rely on the Freedom of Information Act to access additional data generated by FDA with Remoxy. As a result of our recent meeting with FDA, we believe we are no closer today to product approval than we were over a year ago.
“Remoxy remains an odyssey without a homecoming,” said Remi Barbier, President & CEO of Pain Therapeutics. “We had hoped for a fair, neutral and impartial review of the Remoxy data. Instead, we walked out of this meeting feeling a bit disoriented by FDA’s lack of transparency, clarity or helpfulness. It’s a rare occasion when two parties can’t agree on simple math. We can’t work with shambolic regulations. This is not how you win support for innovation.”
Historically, the lead candidate in our pipeline has been Remoxy, an analgesic drug that we conceived, patented, developed and tested in collaboration with corporate and academic partners. Over the years, we have conducted a successful clinical development program for Remoxy, including a large, well-controlled pivotal Phase III efficacy study whose primary endpoints met statistical significance (p<0.05). The clinical safety or analgesic efficacy of Remoxy for its intended purpose is not in question. Its abuse-deterrent properties, however, are subject of a difference of opinion. Abuse deterrence refers to properties that are embedded into an opioid formulation to prevent certain common methods of abuse. During the long development history of Remoxy, we generated nearly 9,000 unique data points in over 50 studies at a cost in excess of $100 million. Studies were designed in consultation with FDA and conducted by independent labs. Collectively, we believe these studies adequately characterize Remoxy’s abuse-deterrent properties. In particular, we demonstrated that the two currently marketed extended-release oxycodone products -- OxyContin® and Xtampza® -- which both benefit from abuse-deterrent label claims, can both be defeated for purposes of abuse in under a minute using common household items. In contrast, Remoxy requires a significant investment of time, effort and equipment to defeat, and even then, results in less release of oxycodone. During our recent meeting with FDA we were informed they believe Remoxy capsules lack abuse deterrence via the injection route of abuse because “oxycodone can be extracted from the product”, regardless of how much time, effort, frustration or equipment is required to so do. We are unable to follow the logic by which a drug product should never release drug. More generally, as the regulatory requirements for Remoxy have changed frequently and suddenly over time, we have experienced significant delays and have incurred unanticipated expenses related to the overall Remoxy development program.
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We believe innovative products such as Remoxy can serve a meaningful social purpose and, potentially, may save lives during the worst drug crisis in American history. By necessity, however, we rely on reasonably predictive regulatory pathways to guide our product candidates through development in preparation for commercialization. We also rely on principles of good governance, in which similar drugs receive similar regulatory treatment under rules that are clear, publicized, and evenly applied. In our experience with Remoxy, the regulatory environment around abuse-deterrence lacks these essential qualities.
There are procedures in place at the FDA and other government agencies to help promote a fair resolution of disputes. Such procedures can be complex and may not be rapid, predictable or even viable. Going forward, we will generally be silent regarding our plans or future expectations for Remoxy, unless a significant material event occurs that compels us to update our public disclosures around this product candidate.
About Pain Therapeutics, Inc.
Pain Therapeutics, Inc. is a clinical-stage biopharmaceutical company that develops novel drugs. Our focus is on neurodegeneration, including an on-going Phase II program with our drug candidate, PTI-125, in patients with Alzheimer’s disease. We own worldwide development and commercial rights to PTI-125 and related technology, including diagnostic, without royalty or milestone obligations to any third-parties. The FDA has not yet established the safety or efficacy of any of our drug candidates. For
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Researchers have found more evidence of a puzzling phenomenon: Older adults who survive cancer seem to be somewhat protected against dementia.
ReplyDeleteA number of studies in recent years have found that cancer survivors have a relatively lower risk of developing Alzheimer's.
The new research adds another layer. It shows that even before their diagnosis, older adults who go on to develop cancer have an edge when it comes to memory performance.
Among the older Americans who were tracked for 16 years, those who developed cancer typically had sharper memory skills -- both before and after the diagnosis -- than those who remained cancer-free.
Researchers said it all supports the theory that some of the biological processes that contribute to cancer may actually protect against dementia.
But the big remaining question is, what are those mechanisms?
"We're really interested in understanding what [they] could be, because it might point the way to strategies to prevent dementia," said senior researcher Maria Glymour, a professor at the University of California, San Francisco School of Medicine.
The study findings are based on more than 14,500 U.S. adults born before 1949. Between 1998 and 2014, they underwent periodic tests of memory function. During that time, 2,250 were newly diagnosed with cancer.
On average, the study found, the people with cancer consistently performed better on memory tests. In the decade before the cancer diagnosis, their memory declined at a 10.5% slower rate than their counterparts who remained cancer-free.
After the diagnosis, cancer patients did typically see a sudden worsening in their memory for a short time. But afterward, their rate of memory decline continued at the same pace as before the diagnosis -- which meant they maintained an advantage over cancer-free older adults.
There are theories as to why the pattern exists: Some of the mechanisms that allow cancer cells to grow and spread may, in the brain, protect cells from dying.
Glymour's team points to the example of an enzyme called PIN1: Its activity is enhanced in cancer, but decreased in Alzheimer's. Among other roles, the enzyme is thought to help prevent the buildup of abnormal proteins in the brain that are the hallmark of Alzheimer's.
But there is a lot of work to do before all the pieces can be put together, according to Glymour. One question is whether only certain cancer types are connected to a lower risk of memory decline and dementia.
In past studies, the link has been surprisingly consistent among different cancers, Glymour noted. "But," she said, "we think that might just be because there were not enough cases of different types of cancer to detect the differences."
If larger studies do show that only certain cancers are tied to slower memory decline, Glymour noted, that could give clues about the underlying reasons.
Dr. Olivia Okereke is director of geriatric psychiatry at Massachusetts General Hospital in Boston. She said the association between cancer and a lower risk of Alzheimer's is puzzling and "sounds counterintuitive" -- since cancer, and some cancer treatments, can actually take a toll on mental skills such as attention, information-processing and short-term memory.
"But these associations have been noted in studies for years now," said Okereke, who wrote an editorial accompanying the research. Both were published June 21 online in JAMA Network Open.
She called the new study a "very useful contribution," because it shows the memory advantage exists before people ever develop cancer, then persists afterward.
That, Okereke said, suggests that "common underlying mechanisms" might contribute to cancer while protecting brain cells.
Treatment with blood pressure medication can improve blood flow to a key brain region in people with Alzheimer's disease, a small clinical trial has found.
ReplyDeleteResearchers stressed that they do not know whether the brain finding can translate into any benefits for patients. But future studies should look into that possibility, they said.
The findings, published June 17 in the journal Hypertension, come from a trial of 44 patients with mild to moderate Alzheimer's. They were randomly assigned to take either the blood pressure drug nilvadipine or inactive placebo pills for six months.
In the end, patients on the drug showed a 20% increase in blood flow to the hippocampus -- a brain structure involved in memory and learning that is one of the first areas damaged by Alzheimer's.
Experts said the study was too small and short-term to know whether the improved blood flow could have any effect on symptoms.
But future research should try to answer that question and should focus on people with early Alzheimer's, said Dr. Jurgen Claassen, the study's lead author.
The research is part of a larger trial that looked at whether nilvadipine could improve Alzheimer's patients' memory and thinking skills. Overall, there was no evidence the drug helped.
But, Claassen explained, patients with early-stage Alzheimer's did show signs of a benefit.
"So a new trial should focus on those patients, and follow them longer -- at least two to three years," said Claassen, an associate professor at Radboud University Medical Center in the Netherlands.
The findings add to a body of evidence on the heart-brain connection, according to Rebecca Edelmayer, director of scientific engagement for the Alzheimer's Association.
Research has shown that some of the same risk factors for heart disease -- including high blood pressure, diabetes and obesity -- are also risk factors for dementia. Last year, Edelmayer noted, a major trial found that tight control of high blood pressure cut older adults' risk of developing mild cognitive impairment -- a precursor to dementia.
t little is known about the effects of blood pressure control in people who already have Alzheimer's. And that's why the new findings need to be followed up, Edelmayer said.
Delete"We don't know if [blood pressure control] may be more of a preventative measure, or if it might have a role in treatment, too," she said.
Why would blood pressure matter in Alzheimer's? According to Claassen, if high blood pressure damages blood vessels supplying the brain, that might increase dysfunction in the cells there.
Brain cells need a large amount of oxygen and sugar to function well, Claassen explained. So about 15% to 20% of the body's blood flow goes to the brain, he noted.
In theory, Claassen said, better circulation to the hippocampus might allow its cells to function better -- even in people with early Alzheimer's. But this trial does not prove that.
The study -- funded by government and foundation grants -- included 44 Alzheimer's patients who were about 73 years old, on average. Half were randomly assigned to take nilvadipine for six months, while the other half received placebo pills.
Not surprisingly, patients on the real drug saw their blood pressure drop by about 11 points, compared to the placebo group.
Meanwhile, specialized MRI scans showed that blood flow to the hippocampus rose by 20%, on average, in the nilvadipine group. It remained stable in other areas of the brain.
For now, Claassen said, the findings suggest that treating high blood pressure in Alzheimer's patients is not only safe, but may even increase the brain's blood supply.
But is that an effect of the medication, or of better blood pressure control in general? It's not clear from this trial, Claassen said.
"Personally," he added, "I think it is the blood pressure lowering itself. That would mean that lowering blood pressure in any way -- including diet and exercise -- might have this effect."
To Edelmayer, the central message is that people "have tools available today" to help preserve their brain health.
"Heart health is very important to protecting your brain, too," she said.