This article appears in THE TENNESEAN (1.21.16)
By E. Teresa Touey, Contributor
The Dementia Discovery Fund is a recently created $100 million global fund to assist small biotechs and entrepreneurial ventures in finding a treatment or cure for Alzheimer’s. The fund is sponsored by the British government, the charity Alzheimer’s Research UK, Johnson and Johnson, Eli Lilly & Co., Pfizer, Biogen Idec and GSK.
“This fund is great news; however, funding for Alzheimer’s is still much lower compared to cancer funding,” said Christopher U. Missling, Ph.D., president and CEO of Anavex Life Sciences Corp., a publicly traded biopharmaceutical company headquartered in New York City.
Anavex’s lead drug candidates, ANAVEX 2-73 and ANAVEX PLUS, a combination of ANAVEX 2-73 and donepezil (marketed under the trade name Aricept), are in a Phase 2a clinical trial for Alzheimer’s. The ongoing, multicenter Phase 2a clinical trial in Melbourne, Australia, started in January 2015, with The Alfred Hospital as the lead site.
To support its operations and advance its clinical trial work, Anavex has secured key funding commitments and had approximately $15.3 million in cash and cash equivalents as of Sept. 30. The company also has filed a $100 million shelf financing and entered into a purchase agreement with Lincoln Park Capital to sell an aggregate of $50 million worth of shares. Anavex previously reported that it is fully funded through completion of the current Phase 2a clinical trial.
The multicenter Phase 2a clinical trial of ANAVEX 2-73 consists of two parts and a total of 32 mild to moderate Alzheimer’s patients. Part A is a simple randomized, open-label, two-period adaptive trial, crossing over between oral (30mg/50mg) and IV (3mg/5mg) administration, lasting up to five weeks for each patient. Part B is an open-label extension for an additional 52 weeks. Initially planned for 26 weeks, Part B, which is now underway, was extended to 52 weeks as a result of requests from patients and caregivers.
Encouraged by its findings, the company looks to advance ANAVEX 2-73 into a larger Phase 2/3 study for Alzheimer’s. It also hopes to initiate a double-blinded, randomized, placebo-controlled Phase 2 trial for ANAVEX 2-73 in an additional indication associated with cognitive impairment.
In July, Reps. Fred Upton, a Michigan Republican, and Diana DeGette, a Colorado Democrat, led passage of the 21st Century Cures Act by a 344-77 vote. Norm Ornstein wrote in The Atlantic, “The act does many things, including making research collaborations easier; promoting therapies like biomarkers to enhance personalized drug treatments, targeted at individuals and not just broadly at diseases; reforming and streamlining clinical trials and making it less challenging and expensive for companies to bring drugs to market; creating incentives for developing drugs for uncommon but deadly diseases; creating an Innovation Fund to encourage young scientists to do path-breaking research; and putting more money into both the National Institutes of Health and the Food and Drug Administration to make these innovations work.”
The bill may impact the mathematics of Alzheimer’s funding. As previously reported by the Alzheimer’s Association, for every $27,000 Medicare and Medicaid spends on caring for individuals with Alzheimer’s, the NIH spends only $100 on Alzheimer’s research. Further, Medicare’s annual expenditures are projected to triple from $300 billion currently to $1.5 trillion by 2050 if no cure for Alzheimer’s is found. Missling said the caretaking costs could put Medicare in a precarious place financially, even possibly bankrupting it.
In early December, an increase of nearly 60 percent for Alzheimer’s research was passed by the U.S. Congress in the federal spending bill, expanding funding from $586 million in 2015 to $936 million in 2016.
The next steps with the potential for impact for Alzheimer’s will happen at the U.S. Senate Committee on Health, Education, Labor and Pensions. Respectfully, I urge Chairman Lamar Alexander to pass this bill in the committee, which he co-leads with ranking member Patty Murray. It will take 22 senators to deliberate to find common ground by giving and taking and incorporating key ideas. Patients and their families know the urgency. Those afflicted regularly confuse past and present memories. Unleashing this act’s potential could capture lost time.
E. Teresa Touey is the editor and publisher of Spotlight on Bio Advances, a blog that showcases the stakeholders in the life sciences sector of the mid-Atlantic states.
This article appears in the January 2016 issue of Cohen Veterans Biosience:
Candy, apple, coin! I repeated these three simple words slowly, clearly and confidently during a brain test at the Office of my wonderful doctor. Jeff, a highly skilled healthcare professional, had given the words to me during the exam as he moved on with other brain tests. He then quizzed my memory.
E. Teresa ToueyRemembering three simple words was my Thanksgiving gift on Monday, November 23, 2015. My heart beat joyfully many times during that appointment. As my physician proceeded with his iterative, thorough, neurological tests on me, I could see positive change. My word recall was matched by better balance, as well as on that day, responding negatively to all symptoms on his brain checklist of 20 questions given to concussion patients during every appointment. I had no headaches, no broken sleep, no anxiety or sadness, no disorientation, and no fatigue. When he asked me to follow his index finger in front of my eyes, I could do so without the feeling of a heavy weight on my eyelids – a noticeable improvement.
As a result, he was able to release me from his care after seeing me every two to three weeks since an automobile accident on July 31st. He reassured me that his staff and he were available by phone if I had any questions in the future. I expressed my gratitude to him and his terrific staff in that moment of good news.
As a writer, researcher, and consultant doing work on national policy with the US Congress on brain disease, I rely on my ability to use my words carefully. Over the last three years, I have organized an annual conference on Capitol Hill to gather experts, members and staff of the US House and Senate, and other advocates on challenges to a law that requires our insurers to treat physical and mental benefits equally or in parity.
My doctor told me during my first visit on August 5th that if I listened to his advice, I could expect full recovery. If I did not, I would delay it. Throughout these weeks, I kept that serious advice front and center of my busy life. As a result, I sense now at more than 85 percent recovery that full recovery will come in 2016.
While struggling to work full-time, I was able to learn the tools of managing not only the headaches, balance issues, memory challenges, sleeplessness, and anxiety, but also the main element of the beginning, the fear. I learned to rest and to pace my exposure to my work on the computer, cell phone texts and television. I did limited workouts through daily walks in my neighbor’s backyard pool and around my borough. I convinced myself to sleep longer in the morning and go to bed earlier at night. I took fish oil and melatonin every day and night. I ate salmon regularly. I learned to let go of stress and focus on what mattered most each day.
At the very start, my physicians seriousness of purpose and tone put the fear of God into me about following his words and advice so that eventually he and his staff saw me as the poster child of a well behaved concussion patient. Yet, this prize is not the most cherished; rather it has become my newly acquired knowledge about unseen wounds.
My doctor works with the athletes of the Philadelphia Union, our region’s professional soccer team, and many county public and private school athletes. Concussions are trending upwards among school athletes throughout the nation. These cases serve also as a point of common ground with concussion cases sustained in car accidents as well as from injuries occurring from war.
Some telling statistics about our returning veterans as reported by the American Psychiatric Association include: 300,000 veterans of the wars in Iraq and Afghanistan have been diagnosed with PTSD; more deaths by suicide than by war combat in 2012; 8 to 20 percent of military personnel deployed in Iraq or Afghanistan experienced a traumatic brain injury; 20 percent of national suicides are completed by veterans; military suicide are at their highest rate in ten years; and traumatic brain injuries can increase suicidal thoughts and behavior.
In December 2015, Cohen Veterans Bioscience’s CEO Magali Haas sponsored my third annual roundtable on the Mental Health Parity Addiction and Equity Act of 2008. She co-led a panel with retired US Army Colonel Dallas Hack on the need for a national model to treat the veterans with PTSD and TBI. Cohen Veterans Bioscience is harnessing the power of high-performance computing and data analytics to discover and develop predictive disease models from integrated biomarker, biosensor, and phenotypic data. The hope is that, in the next three years, there will be a first generation of diagnostics for PTS and TBI. “Once we have a better understanding of the science of PTS and TBI, we can advance a new pipeline of therapeutics and improve the delivery of medical care,” says Dr. Haas.
As I said to my physician throughout last year, my personal life has brought me a real lesson of empathy and insight into the challenges of these veterans as well as other patients suffering with concussion, which I can now bring to my professional work. This motivation is more than enough to follow the good doctor’s advice while hoping and working for FULL RECOVERY in 2016.
Medicaid enrollees were promised by Governor-elect Wolf a roll back of Governor Corbett’s rejection of Medicaid expansion under the Affordable Care Act which contains stronger mental healthcare benefits. The Center for Medicare and Medicaid Services expects to release guidance on how the final rule of the Mental Health Parity Addiction and Equity Act of 2008, which requires insurers to treat physical and mental health benefits on par, may apply to Medicaid.
The painstakingly stark reality of brain diseases is their persistent, patient, pernicious character: diverse, pervasive, demanding growth path of biology surrounded by political and cultural stigma. The Unseen economic consequence of it equates to the world’s most expensive disease with estimated 2010 cost worldwide of $2.5 trillion for 2 billion patients.
Costs mount when patients are robbed of the ability to earn a living during their most productive years. Veterans are impacted. Three hundred thousand of those returning from Iraq and Afghanistan have been diagnosed with PTSD accessing care through the Veterans Administration. Some return to private sector jobs with private health care benefits affected by the parity law. How it goes for those who have served us will provide a roadmap for all brain disease patients over the next decade. Most experts agree care must be integrated between mind and body in our research for medical answers as well as our financing of it.
One model is being used by One Mind, a foundation founded by former Rhode Island Congressman Patrick Kennedy. It is focused on developing accelerated diagnostics, treatments, preventions, and cures for brain injury and brain disease. One Mind’s CEO, General Chiarelli approaches the challenge by finding ways to incentivize cooperation, sharing and collaboration amongst researchers. “They’re putting down their competitive instincts,” he said of the researchers, “and working together for the good of the country.”(Politico) He was told by experts throughout the nation “it would be years, if ever, before more advanced tests could be developed for PTS(D). So, Chiarelli directed his energies toward expanding mental health treatment programs in war zones and on domestic bases, and he pushed military doctors to explore the efficacy of alternative therapies”
In USA Today on June 28, 2014, NJ based Kennedy, and Husseini Manji, global head of neuroscience at Janssen Research and Development, LLC, a Johnson and Johnson company, offered a three point approach , “NIH funding of brain science via the Brain Initiative, enforcement of the 2008 Mental Health Parity Addiction and Equity Act known as the parity law, and coordination of effort between the for profit, not for profit, and government sectors”.
Another solution comes fromSenator Cory Booker(D-NJ) and Senator Dean Heller(R-NV) who included within the veterans reform bill of $17 billion signed into law in July 2014, an extension of a PTSD program. Cape May veterans convinced Senator Booker not only to advocate to extend the unemployment benefits but also to extend the $2 million funding to this proven, effective healthcare program.
As well, Representative Tim Murphy(R-PA) is forging bi-partisan support for HR3717, ‘Helping Families in Mental Health Crisis Act of 2013’ , with Rep Eddie Bernice Johnson(D-Tx). The bill would create an Assistant Secretary’s position to track spending by all federal departments on mental healthcare. Respectively serving in the House as the only clinical psychologist and psychiatric nurse, each brings deep expertise attracting co-sponsors with law enforcement like Representative Patrick Meehan.
Rachel Pruchno, an endowed professor of medicine at Rowan University and author wrote in The Philadelphia Inquirer, it “would make life better for people with mental illness, their families, and society. “…More and better outpatient treatment programs would exist, primary-care physicians would be trained to care for people with mental illness, and behavioral-health services would improve. Parents of adult children with mental illness would be able to talk with their child’s physicians, empowering them to help with treatment decisions when their child is in crisis”.
Emergency rooms and jail cells have seen rising costs and investment over the last decade rationing care for brain disease to these growing “hot spots." Simultaneously, public-private partnerships have invested in life sciences clusters creating value for our economy and our health through its regulated drugs, devices, and diagnostic tools. Governor Wolf will need to monitor whether giving broader access explodes costs. With one in four families affected, and with a healthcare system that rewards rationing over collaboration, balancing accountability on costs while exploiting our assets of innovation could provide a model for the nation who voted for split government in hopes of progress.
The aftermath of the 2008 world economic crisis yielded a new reality of extremely short-term horizons for life sciences companies seeking venture capital for growth. BioBDx, formerly of Plymouth Meeting, PA and Westford, MA, navigated this change. Byron Hewett, CEO and Chairman, and Calvin Sumner, MD, Chief Medical Officer, continued promoting the company’s Quotient® System to physicians, mental healthcare professionals, and investors. Eventually, they found a well-matched buyer when Pearson “announced (on August 27, 2013), the acquisition of substantially all of the assets of the BioBehavioral Diagnostics Company (BioBDx), the developer and marketer of the Quotient® System, the first U.S. FDA-cleared tool for the objective measurement of hyperactivity, impulsivity and inattention as an aid in the assessment of attention deficit hyperactivity disorder (ADHD)”.
Byron Hewett of BioBDx, said, “As a part of Pearson, Quotient product development, clinical trials and commercial activities will be funded more robustly and the product will be offered to an even broader audience. This will accelerate awareness and adoption, improve efficiency of patient visits and, ultimately, raise the standard of care for ADHD. Our team has deep expertise in the diagnostic world, and we believe Pearson will benefit from that expertise in the years to come.”
“We are taking immediate steps to strengthen support for current Quotient customers and expand our outreach to healthcare professionals,” said Aurelio Prifitera, President and CEO of Pearson Clinical Assessment. “We also look forward to introducing the Quotient ADHD Test to mental health and education professionals in both clinical and school settings.”
ADHD is the most common neurobehavioral condition in children, and symptoms persist into adulthood in approximately 60 percent of cases. It affects approximately 6.7 million children and adolescents and nearly 15 million adults in the United States. ADHD makes it difficult for a person to control behavior and may have serious consequences, including failure in school, family stress and disruption, depression, problems with relationships, substance abuse, delinquency, risk for accidental injuries and job failure. Early identification and effective treatment are extremely important. As such, ADHD is a condition that is central to Pearson’s vision to meet the educational needs across a spectrum of individuals.
The Quotient ADHD Test quantifies the severity of deficits in brain functions related to the symptoms of ADHD and helps clinicians to accurately diagnose and efficiently manage the condition through repeat assessments at critical decision points. The Quotient ADHD Test is currently used in pediatric, neurology and psychiatry offices throughout the United States. (SOURCE: PRWEB)
Another unique challenge to BioBDx’s growth was the five year delay in the release of the final rule for the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act. Pete Domenici, a former U.S. senator from New Mexico, and Gordon H. Smith, a former U.S. senator from Oregon, wrote a pre-final rule release in a Washington Post op-ed piece on April 12, 2012, “In, 2008, Congress passed and President George W. Bush signed the…Act. This law, which garnered bipartisan support, requires that large group health plans and Medicaid managed-care plans provide coverage for mental or substance-use disorders on par with the coverage offered for physical ailments. But when any law is passed, the federal government must implement and enforce it to make its benefits and provisions a reality.
President Obama voted for the bill as a U.S. senator, and all indications are that he remains supportive. Yet regulatory action has stalled since 2010. The final rule that would provide clarity to the millions who have a mental illness or substance-use disorder, and to their employers, has not been issued. This has created uncertainty and confusion for employers over what they must cover and when parity applies”.
Physicians who diagnose and treat ADHD as well as those physicians who use the Quotient® System either had denied or delayed payments by insurers. Former Rhode Island Congressman Patrick Kennedy, founder of One Mind for Research and House sponsor of the law, met with BioBDx executives. Financial details regarding the impact of the law’s delayed implementation were discussed. Patrick Kennedy shared his plan to press forward on parity implementation. Within a few weeks, the tragedy at Newtown placed mental healthcare and parity firmly onto the national agenda. Hewett and Sumner discussed with Pearson Clinical Assessment’s leaders, Aurelio Prifitera, CEO, and Travis Millman, VP, New Business & Innovation Group, the impact of the law. Shortly afterward, Pearson agreed to sponsor a meeting in Washington, DC with the key patient advocacy groups who support the implementation of mental health parity. The final rule was released by the Obama administration on November 8, 2013 enabling a productive roundtable discussion in Washington DC attended by the major stakeholders sponsored by Pearson, National Alliance for Mental Illness, and Spotlight on BIO Advances generating a response to the Department of Labor’s FAQ in early January 2014.
Profile: Emerging Biotechnology Company in Pennsylvania
NuPathe of Conshocken, Pennsylvania, offers a strong model of an emerging biotechnology company. Its growth path illustrates the positive impact of communication and feedback between developer and regulator during the new drug application process.
Its CEO, Jane Hollingsworth, commented after a presentation to investors at the winter conference held by BIO,“We welcome the evolution in the FDA’s approach to increasing the two-way communication regarding drug applications. Increased dialogue and interaction are always helpful and should certainly improve the regulatory process.”
In 2010, NuPathe’s initial public offering raised the company an additional $50 million, accessing more diverse capital. The IPO was motivated by NuPathe to take advantage of favorable migraine market dynamics to commercialize its migraine patch. The patient pool for the patch turns to the internet to find solutions to one of the major symptoms of migraine, considerable migraine-related nausea. Marketing the migraine patch became self-evident.
NuPathe’s website elaborates, “If approved, NP101 will be the first transdermal patch for the treatment of migraine. NP101 actively delivers sumatriptan, the most widely prescribed migraine medication. In clinical trials involving more than 10,000 applications, NP101 offered patients fast onset and sustained relief of debilitating migraine symptoms including headache pain and migraine-related nausea (MRN). It utilizes SmartRelief, our proprietary transdermal delivery technology, that rapidly transports medication through the skin using a process called iontophoresis.”
Early-stage capital helped NuPathe get to the innovative product candidate attracting more venture capital from Safeguard Scientifics, Quaker Partners and SR One, GlaxoSmithKline’s venture group. Early-stage financing came from friends of management, management, greenhouse money from BioAdvance, and Ben Franklin Partners Technology Partners of Southeastern Pennsylvania.
Now, the market is primed to be developed. The core patient population is both working age, 25 to 55 year old, and social media sophisticated, thus a lower percentage of NuPathe’s capital will be used to market the product than has historically been the case with many other products. Staying nimble, efficient and fast as a management team has led to NuPathe achieving the hard technical challenge of developing the transdermal technology.
The management team brings complementary skills. Jane Hollingsworth is a lawyer with deep experience in the pharmaceutical industry. Terri Sebree is a neuroscientist with a long track record of getting product candidates approved by the FDA. Their prior joint, co-founding venture at Auxilium gave them the experience to develop a model for a biotechnology company that has emphasized an industry trend: Big Pharma is partnering with biotechnology companies to fill its pipeline. NuPathe has grown slowly and surely, developing a pipeline of therapeutic candidates as well as the financial structure to support its growth. In common, Hollingsworth and Sebree have strong leadership skills and consider problem solving an important element in drug development. Also, they have been patient with the process. At this point, they have invested six years.
Where does its product stand in the regulatory process? NuPathe completed a new drug application in the fall of 2010. It received an August 2011 complete response letter from the FDA, which included additional questions about the application. As a result of a meeting with the FDA to reach an agreement about resubmission details, NuPathe will resubmit the new drug application in the next several months, starting a new clock for a six-month review.
In the closing conference session, Dr. Stephen P. Spielberg, deputy FDA commissioner, talked about the modernizing the regulatory process. “Since my career began 35 years ago in the 1960s, science has changed. We have a huge change of our understanding of biology. The innovation and the technology have created a sea change. Science is complex and at times overwhelmingly so and it has outpaced our sociology.” The challenge to do so while meeting the standards of efficacy, safety and quality impacts all stakeholders.
As the FDA application is processed, NuPathe continues to develop contacts with migraine experts, potential business development partners, and investors interested in its migraine patch, SmartRelief transdermal technology and two other product candidates using the company’s long-term biodegradable implant technology: one for Parkinson’s disease and one for schizophrenia and bipolar disorder.
And forward, the clock moves while the national BIO organization continues to work on legislative efforts in two areas – renegotiation of the fifth series of PDUFA allowing the FDA to collect fees from companies that produce human drugs and biologics to support limited FDA activities around the drug review process and the TREAT act which would create an accelerated approval pathway at the FDA for treatments for diseases or conditions that are serious or life-threatening.