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 

Tazemetostat

tazemetostat
Epizyme Submits New Drug Application to the U.S. FDA for Tazemetostat for the Treatment of
Patients with Epithelioid Sarcoma

CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 30, 2019-- Epizyme, Inc. (Nasdaq: EPZM), a late-stage biopharmaceutical company developing novel epigenetic therapies, today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for accelerated approval of tazemetostat for the treatment of patients with metastatic or locally advanced epithelioid sarcoma not eligible for curative surgery. Tazemetostat is an oral, first-in-class, EZH2 inhibitor discovered by Epizyme and being developed for a range of cancers and treatment settings.
This NDA submission follows a recently conducted pre-NDA meeting held with FDA, in which the Agency considered the proposed clinical package to be sufficient for inclusion with the NDA. The submission is based on updated tazemetostat efficacy and safety data from 62 patients enrolled in the epithelioid sarcoma cohort of the Phase 2 clinical trial, which will be reported in an oral presentation at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting. The company’s ongoing Phase 2 study cohort is the largest prospective clinical trial in epithelioid sarcoma with any approved or investigational anticancer treatment to date.
“Epithelioid sarcoma is a rare and aggressive cancer that affects people in the prime of their lives, and we are very pleased to have recently submitted the NDA for tazemetostat for the treatment of people with this devastating cancer,” said Dr. Shefali Agarwal, chief medical officer of Epizyme. “If approved, we believe tazemetostat has the potential to change the care of patients with this disease. We are incredibly grateful to the physicians and clinical teams who have helped advance tazemetostat to this stage, and, most notably, to the patients and caregivers who have participated in our clinical trials along the way. We look forward to continuing to engage with the FDA as we work to bring tazemetostat to patients and physicians in the U.S.”
To support a full approval of tazemetostat for epithelioid sarcoma, Epizyme plans to conduct a global, randomized, controlled trial, that it expects to begin in the second half of 2019. The final design of the study is subject to alignment with FDA, and the company plans to disclose details once it has reached alignment with FDA and the NDA submission has been accepted for review. The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing.
“At Epizyme, our mission is to deliver new treatments for patients with cancer and other serious diseases, and today we stand one significant step closer to achieving that,” said Robert Bazemore, president and chief executive officer of Epizyme. “This submission is the culmination of years of hard work by our entire team, and I wish to congratulate them all on this accomplishment. Our epithelioid sarcoma program is strategically valuable to Epizyme and helps streamline our planned NDA submission in the fourth quarter, for patients with follicular lymphoma. Over the coming months, we have multiple anticipated clinical data and regulatory milestones, and we are well underway with commercialization readiness activities to support the potential launch of tazemetostat and our transition to a commercial-stage organization. 2019 is set to be a transformational year for Epizyme, and I am enthusiastic for our continued progress.”
About Epithelioid Sarcoma

Epithelioid sarcoma is an ultra-rare soft tissue sarcoma characterized by a loss of the protein INI1. Patients are most commonly diagnosed as young adults, between 20 and 40 years of age. Median overall survival from initial diagnosis is 30 months. Epithelioid sarcoma becomes more aggressive after recurrence or metastases, with a typical survival of less than one year for patients with metastatic disease.
About Epizyme, Inc.

Epizyme, Inc. is a late-stage biopharmaceutical company committed to rewriting treatment for cancer and other serious diseases through novel epigenetic medicines. Epizyme is broadly developing its lead product candidate, tazemetostat, a first-in-class EZH2 inhibitor, with studies underway in both solid tumors and hematological malignancies, as a monotherapy and combination therapy in relapsed and front-line disease. The company also is developing a novel G9a program with its next development candidate, EZM8266, which is targeting sickle cell disease. By focusing on the genetic drivers of disease, Epizyme's science seeks to match targeted medicines with the patients who need them. For 

Health Highlights: March 11, 2019

Here are some of the latest health and medical news developments, compiled by the editors of HealthDay:
FDA Approves 1st Immunotherapy Drug for Breast Cancer
The U.S. Food and Drug Administration has given its blessing to the first immunotherapy regimen for breast cancer.
The combination of immunotherapy (Tecentriq) and chemotherapy (Abraxane) was given accelerated approval for triple-negative breast cancer that is locally advanced or has spread, cannot be surgically removed, and has cells that have a protein called PD-L1, CNN reported.
A study
ed last October in the New England Journal of Medicine found that median progression-free survival (length of time a patient's cancer does not worsen) was 7.4 months among patients who received the combination therapy, compared with 4.8 months among those who received chemotherapy with a placebo, the FDA said Friday.
The study was funded by Genentech Inc., the maker of Tecentriq.
"This is the first time immunotherapy has worked in such a difficult to treat cancer, and is a huge step forward for these breast cancer patients," study author Dr. Peter Schmid, from Queen Mary University of London, said in a statement last October, CNN reported.
The accelerated approval is just the start, noted Dr. Otis Brawley, professor of oncology and epidemiology at Johns Hopkins University.
"The FDA has approved it based on progression-free survival with the hope that later on ... data will show that the treatment actually makes women live longer," Brawley told CNN.
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Flu Season May Have Peaked: CDC
It looks like the flu season has peaked in the United States, though there's been a recent rise in the number of cases involving a more severe flu strain.
Flu was widespread in 48 states last week, down from 49 the previous week, according to a U.S. Centers for Disease Control and Prevention update released Friday. CDC experts believe there's a 90 percent chance the flu season has peaked, the Associated Press reported.
Several flu strains often circulate in the United States at the same time, but one strain typically dominates.
A milder strain of flu has been the most common cause of cases this flu season. But over the last two weeks, about 60 percent of flu virus samples tested were a strain called Type A H3N2, which tends to cause more hospitalizations and deaths, especially in the elderly, the AP reported.
There have been 20,000 to 30,000 flu-related deaths in the United States so far this winter, about 300,000 flu-related hospitalizations, and around 25 million flu illnesses, according to the CDC.

Nutritional Supplements Don't Ward Off Depression: Study

 Taking vitamin pills and other supplements won't prevent depression, but promoting better eating habits might help, new research suggests.
The study included more than 1,000 overweight or obese people in the United Kingdom, the Netherlands, Germany and Spain who were at risk for depression, but were not currently depressed.
Excess weight is often linked with depression, the researchers noted.
Half of the study participants took daily supplements containing folic acid, vitamin D, omega-3 fish oils, zinc and selenium. Half took a placebo pill.
Half were also counseled about their eating habits and urged to limit snacking and follow a healthy Mediterranean-style diet.
In a one-year follow-up, the researchers discovered that the supplements worked no better than the placebo in helping ward off depression.
Similarly, the counseling was not effective overall, though it seemed to help prevent depression in participants who attended a recommended number of sessions.
That suggests counseling works only if people get an adequate "dose" of therapy and make significant changes in their diet, according to the study
ed March 5 in the Journal of the American Medical Association.
"Because depression is such a common problem, finding effective and widely available ways to prevent depression at a population level is an important goal," said study co-author Ed Watkins.
He's a professor of experimental and applied clinical psychology at the University of Exeter in England.
"Diet and nutrition held promise as one means to reach large numbers of people. However, this trial convincingly demonstrates that nutritional supplements do not help to prevent depression," he said in a university news release.

Vets Who Get Opioids From VA, Medicare at Higher Overdose Risk

 Many military veterans can get prescription opioid painkillers from both the VA and Medicare, putting them at nearly triple the risk for an overdose, new research warns.
The finding could have implications for a huge number of vets: Roughly eight in 10 VA-covered patients have additional private or public health insurance coverage. About 51 percent have Medicare, and about one-third of those receive Medicare Part D drug benefits.
But the problem may be more about poor oversight than addicted patients trying to game the system, noted study author Dr. Walid Gellad, a researcher with the VA Pittsburgh Healthcare System.
"Only in some limited circumstances -- and we don't know how many -- is this purposeful behavior by a patient to try and get additional opioids," he explained.
"I would not think of this as 'double-dipping' or 'being caught,'" Gellad added. "In some cases, receiving opioids from both systems could have happened at different times, as veterans got care in one system first, and then in another system later, or they go back and forth between VA and the private sector. In some cases, the opioids are prescribed at the same time, sometimes unintentionally, and sometimes intentionally."
Gellad and his team found that more than 3 million veterans filled at least one opioid prescription (either through the VA or another insurer) during the time period from July 2011 through December 2013.
To see how dual health insurance coverage might influence overdose risk, the team first examined the records of 215 veterans who died from an overdose between 2012 and 2013.
Their average age was 57, most (90 percent) were male and most (84 percent) were white. All had both VA and Medicare Part D health care coverage for at least six months prior to their deaths.
For comparison, the investigators also assessed opioid prescription patterns among a "control group" of more than 800 living vets of a similar age, race, health status and gender.
About 28 percent of those who had died due to an opioid overdose had obtained their meds from both the VA and through Medicare Part D. This compared with just 14 percent of the control group, the researchers found.
Still, Gellad stressed that systemic changes that curtail getting opioids from multiple sources have been implemented by the U.S. Department of Veterans Affairs since the study ended in 2013.
For example, he noted that "the VA has instituted requirements to check prescription drug monitoring programs, which should alert physicians to instances when opioids are prescribed in different systems."
But, "for this to work to reduce the risk of overdose, clinicians have to actually check, and they have to do something with the information when they find it," Gellad added.
"Ultimately, I think we will see automated alerts that will alert clinicians to a medication prescribed in one system if it, or an interacting medication, is also being prescribed in another system," Gellad said. "But for that to have an impact, it has to alert at the point of prescribing, which is not possible yet within [the] VA or outside [the] VA."
The report was
ed online March 12 in the Annals of Internal Medicine.
Dr. Carolyn Clancy, Deputy Under Secretary for Discovery, Education and Affiliate Networks with the VA in Washington, D.C., co-authored an accompanying journal editorial.
Clancy pointed out that "because of VA's existing robust and extensive patient record system, the department has had significant success in reducing opioid use and overdose risk."
The VA has been tracking problems related to dual access to medications "for some time," she said.
"That's why the department is constantly working to improve coordination with community providers," Clancy noted. "Especially through the implementation of electronic health record modernization."
And going forward, she said, the VA hopes to augment the current screening process afforded by state prescription drug monitoring programs, by "seeking to develop [its own] electronic system to automatically check all state prescription drug monitoring programs for each veteran to further improve care coordination."

Chickens Help Scientists Pinpoint Origin of Rare, Deadly Virus

 Much like a canary in a coal mine, Florida chickens have warned researchers of a rare but deadly mosquito-borne virus in their midst.
These sentinels have revealed that eastern equine encephalitis virus (EEEV) originates in the state's panhandle and then spreads as far north as Nova Scotia, Canada, the new study found.
"In the region of the panhandle, this is year-round. You can get exposed to this virus by infected mosquitoes year-round," said lead researcher Suman Das, an associate professor of infectious diseases at Vanderbilt University Medical Center in Nashville, Tenn.
Now that scientists know where the virus comes from, they can focus prevention efforts in mosquito-ridden areas of the panhandle, Das said.
"This is, I would say, the deadliest virus we are potentially exposed to in the United States," Das said. "It's been lurking around in the country about 20 to 30 years, and the mortality rate is about 40 percent."
EEEV, which sickens humans and horses, is rare in people, with only about 70 cases reported since 2008. But experts fear the infection rate could rise as global warming extends the reach of mosquito populations farther north.
The virus causes brain swelling in its human victims, and even survivors can pay a long-lasting price, Das said.
"Even when people don't die, in those cases, there is a lot of neurological disease and ultimately, they die earlier," Das said.
EEEV infection can result in severe intellectual impairment, personality disorders, seizures and paralysis, according to the U.S. Centers for Disease Control and Prevention.
Previous research had shown that EEEV spreads outward from Florida, but up to now no one had been able to say what part of the state served as the virus' wellspring, Das said.
Northern states track mosquito-borne viruses by using insect traps and then directly testing the pests for the presence of pathogens, but that method doesn't work in mosquito-beclouded Florida, Das said.
"There are much fewer mosquitoes in the northeastern states compared to Florida. You'd be looking for a needle in a haystack," he explained.
So, Florida turned to chickens to help track the progress and source of EEEV and other viruses.
Between 2005 and 2016, 38 of Florida's 67 counties participated in the state's sentinel chicken surveillance program. Flocks of chickens are strategically placed in coops around the counties, and their blood is regularly tested for viral infection, Das said.
"If a chicken is exposed to EEEV, it doesn't kill the bird but they will make antibodies" against the virus, he explained.
Over 12 years, the chickens demonstrated that the virus is a year-round phenomenon in the panhandle but occurs only seasonally in northern and north-central regions of Florida, Das said.
That probably means EEEV spreads from the Florida panhandle.
"We think that the panhandle, the source of the activity, seeds to the rest of the state, and Florida is the source for the Northeastern United States," Das said.
Thus, mosquito control efforts focused on the Florida panhandle might stand a chance of killing EEEV in its crib, he said.
"That the Florida panhandle appears to be a year-round nexus of transmission is important for epidemiological understanding of this virus and its mosquito vector," said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore.
Adalja, who wasn't involved with the research, said the findings underscore the importance of aggressive mosquito control in at-risk areas and the need for eastern equine encephalitis to be considered in patients who live in or travel to areas where it has been shown to flourish.
The new study was
ed March 11 in the American Journal of Tropical Medicine and Hygiene.

'Daddy-Do-Overs': Men Increasingly Getting Plastic Surgery

 A face-lift for Father's Day, anyone?
It could happen: A new report finds many more men are taking advantage of the same plastic surgeries that have long been associated with women.
The midlife decision by men to try a face-lift or other procedure has been nicknamed the "Daddy-Do-Over" -- referencing the "Mommy Makeover" for women.
Whatever it's called, "men are embracing the idea of surgery more than before," said Dr. Alan Matarasso, president of the American Society of Plastic Surgeons (ASPS).
He stressed that the average man approaching or in middle age might have different reasons for wanting a nip or a tuck, compared to his female peers.
"Obviously, men don't go through the same physical changes that women experience during pregnancy and post-pregnancy, but their lifestyle does change, which can impact their appearance," Matarasso said in a society news release.
"Diet and exercise patterns fluctuate, and they don't sleep as much," he added. "Men notice their body changes due to aging and parenting, and it starts to look completely different in their 30s and 40s. That is the point of a Daddy-Do-Over."
In fact, according to the ASPS, more than 1 million men had cosmetic surgery in 2018, a 29% increase since 2000.
Like women, men are typically getting body contouring and facial procedures to enhance their physique and keep the dreaded "dad bod" at bay. The most popular procedure for men was rhinoplasty -- a "nose job" -- with 52,000 of the procedures performed on men in 2018, the ASPS said. That was followed by eyelid surgery, liposuction, breast reductions (24,000 cases) and hair transplants.
Botox injections are also popular with men, with nearly half a million procedures performed last year. Another 100,000 "filler" procedures were performed on men in 2018, the ASPS said.
One case in point is 57-year-old Scott, a restaurateur in New York City who said he couldn't get rid of his spare tire.
"I realized I was never going to lose the weight on my own," he said in the news release. "Plastic surgery is a personal decision, but I know guys my age who have done different cosmetic procedures. I think an open dialogue about plastic surgery is becoming more acceptable, especially for men."
Men are increasingly getting plastic surgery to help them advance their careers and compete in the workplace, Matarasso said.
Dennis, 59, is a creative director working in the New York City fashion industry. He was lean and fit, but still struggled with fat accumulating in certain areas.
"I've been in fashion my entire career, and it makes me feel good when I walk in the room and I don't feel as if I look 60 in a room of 25- to 30-year-olds," Dennis said in the news release. "I always carried weight in my neck and chin, and my droopy eyelids made me look more tired than I actually was."
He underwent an eye lift and chin surgery and says he's "gained unexpected confidence from the small changes."
Of course every surgery comes with risks, plastic surgery included, so Matarasso stressed that men consult at length with an accredited, experienced surgeon to maximize safety.