Gina Hagler — Gina Hagler

An emerging drug development model has the potential to reduce the cost of treatments for rare diseases.

What is a Rare Disease?

The definition of a rare disease varies by country, with the consensus that a rare disease or condition is one that affects far less than 1% of the population. Because each rare disease affects so few people, the traditional drug development model has proven to be inadequate when applied to them. Despite the provisions of the Orphan Drug Act, enacted in the United States in 1983 to stimulate investment in such treatments, the development cost for rare disease treatments has been prohibitive, making it virtually impossible for a drug manufacturer to recoup their investment during the time the treatment is under patent. As a result, the 350 million people worldwide who are affected by one of the approximately 7,000 rare diseases and patients are left without the likelihood of a viable and affordable treatment in their lifetime.

rare-disease-day2 — Photo Credit: World Rare Disease Day

How Much Does It Cost?

The current drug development process is time-consuming and complicated because it can take years of research to identify a likely treatment, formulate it for use by patients, and bring it through trials and onto the market. The process is also expensive. A recent JAMA study set the mean investment (inclusive of the cost of failed trials and research & development) at $1.4 billion. Treatments that are granted Orphan Drug Status by the FDA can cost considerably less to gain approval (read more). but If a pharmaceutical company is working on a drug without Orphan Drug status is to remain a viable business and continue its work on other drugs, it must recoup this money during the remaining life of the drug’s patent.

This is difficult at best as, despite the fact that there are thousands of rare diseases affecting millions of people, the total population constituting the market for a specific drug is typically not large enough to offset the costs incurred in bringing that drug to market. The result is a situation in which there is a financial disincentive for pharmaceutical companies to pursue treatment options for rare diseases. Because of this, reducing costs is vital.

How Can We Reduce These Costs?

Historically, due to the total cost, long development time, and short exclusivity period once the product is approved, there has been no viable way to reduce the costs associated with developing a new drug or recoup the cost after the drug is approved. Today, the growing field of biopharmaceuticals holds promise for the development of treatments for rare diseases, about 80% of which are genetic in nature. Gene editing and other tools of biotech can be brought into play as potential game-changers. Whether a conventional treatment or a biopharmaceutical treatment is being explored, the need for funding in some areas remains unchanged, i.e, the research and development effort, the formulation of an effective delivery system, and the design and implementation of trials that are populated with those affected by the disease.

The rapid progress made in developing such biopharmaceutical tools as AGT’s gene delivery platform in recent years offers an opportunity to reduce the financial investment in a new treatment by reducing the costs associated with these activities by working to:

1. Maximize the Return on R&D Expenditures

One way to lower the costs of treatments for rare diseases is to minimize the expenses associated with research and development. Some large biopharma companies attempt to spread R&D costs across a range of drugs by pursuing promising research in several areas and matching their findings with existing problems when the research indicates they have a potential treatment. This approach to drug development is not specifically done with the intention of finding a treatment for a particular rare disease. As a result, the company’s overall profitability is enhanced by dedicating its research to scientific discovery rather than the pursuit of a treatment for one specific condition.

For rare diseases, this is not the most expedient way to pursue a cure; those awaiting a treatment usually have a limited window in their lifespan during which treatment will make a meaningful difference. Organizations and labs that are dedicated solely to research for a specific rare disease must put their focus on one target through a limited number of possible pathways. This focuses their R&D dollars on one disease, making it more likely that a treatment will be developed in a relatively short amount of time. Since this essential work is costly, the only realistic way to maximize the return on this R&D is to achieve a possible treatment in the shortest amount of time, then move forward with a proven delivery system and remote trials.

2. Make Use of Orphan Drug Status When Possible

The Orphan Drug designation helps to decrease the cost of rare disease development through tax credits. The designation also provides exclusivity for seven years after approval. To read more about the benefits from the Orphan Drug designation and incentives, see “Benefits of FDA Orphan Drug Designation: What You Need to Know.”

3. Make Use of a Proven Delivery System

Many companies in the life science industry have chosen to specialize in one role. American Gene Technologies (AGT) has claimed its place as a company that delivers the solution to the patient with what Jeff Galvin, AGT founder and CEO, describes as “genetic tools and reusable components that can be mixed and matched to cure a myriad of diseases.”

In 2019, AGT received an FDA orphan drug designation for the treatment of phenylketonuria (PKU) using its proprietary, lentiviral vector-based technology. If successful, AGT’s lentiviral vector approach will provide a permanent cure for more than 16,000 people living in the U.S. alone. Galvin says, “We believe this orphan designation will enable AGT to formally shape and advance its PKU program.”

The first clinical trial utilizing AGT’s technology will be for a functional cure for HIV/AIDS, a disease that is far from rare. However, the tools and know-how developed for its HIV program will benefit AGT’s work in PKU as well.

Both of these potential cures utilize the delivery system Galvin spoke about In a recent TEDx Talk given at Georgetown University. As Galvin stressed, utilizing this existing delivery system has made it possible to go from the R&D stage to clinical trials with very little additional time or money invested.

4. Make Remote Participation Possible

Given that rare diseases affect very few people around the world, the costs associated with the logistics of the trials that are required to prove the efficacy and safety of a treatment are significant factors contributing to the cost of the treatment. Harsha Rajasimha, Ph.D., founder and CEO of Jeeva Informatics Solutions Inc., stresses that “the top thing to know about treatments for rare diseases is that access depends on the patient’s ability to travel and their zip code. With 95% of rare diseases still without any FDA approved therapies, thousands of treatments are still in clinical trials.

Almost all of these clinical trials are sponsored by biopharmaceutical companies in the USA and the EU. So, there is an inherent bias in who gets to participate and access these potentially life-saving therapies before they are approved years down the road. We are developing Saas [Software as a Service]solutions to reduce this travel burden for patients in clinical trials by 50% to 80%.” The ability to participate remotely in a trial will not only make it easier for distant patients to participate in trials but it also reduces the logistical costs of these trials significantly.

Bottom Line: The Cost of Rare Disease Treatments will Decline

As the search for treatments for rare diseases continues, the advances made in gene and cell therapy bode well for these largely genetic disorders. By combining research with the benefits of Orphan Drug status, new delivery methods, and remote participation in trials, a new drug development model is evolving. This model makes use of efficiencies that did not exist until recently. Their part in bringing about a decline in the initial investment for drug development makes it possible for biopharma companies and labs to pursue treatments that would have been prohibitively expensive in the past. As Jeff Galvin wrote in a recent article on biopharmaceuticals, “Gene and cell therapies are making an impression on the entire medical community and even the public. The possibilities are endless. This is no longer science fiction. It is the future of medicine. And that future is bright.”

Published on AGT

There are nearly 7,000 rare diseases affecting approximately 1% of the global population. When your child is affected with one of these rare diseases, and it is so rare it does not even have a name, what do you do? Amber Freed’s decision was to fight like a mother. She recently shared with us what that means for her and her son, Maxwell.

Birth and Growing Concerns

Maxwell and his sister, Riley, were born on March 27, 2017. After several years of trying, the twins’ healthy birth was a perfect start to life as a family. “But around four months, I just noticed Maxwell wasn’t doing the things that Riley was doing,” Amber said. “I filled out their baby books every month. I’d say Riley rolled over. Riley likes the yellow rattle. And one of the stranger things to stand out was that Maxwell had never used his hands. And he constantly stared at his crooked pointer finger.” When Amber went to the doctor, she’d say, “My baby keeps staring and his finger and he’s not rolling over and meeting his milestones. The doctors would say, ‘Amber, you’re crazy. You’re a new mother. You’re Type A.” She would agree and say, “Yes, that’s all true. But my gut is telling me that something is really wrong here.” They’d reassure her and send her home, telling her they would see them next month. Month after month passed in this way. But when Maxwell and Riley had their nine month checkup, Amber said, “I could see the doctors had fear in their eyes. And my sweet pediatrician, that is the most wonderful man in the world, had a little bit of panic as he said, ‘Okay. Why don’t we have him evaluated by a neurologist? Maybe he should go there.” With that, their diagnostic odyssey in which they visited every imaginable type of specialist began.

Is it His Vision?

The fact that Maxwell was always staring at his finger, continued to concern Amber. She took him to an ophthalmologist to be sure his vision wasn’t impaired. The ophthalmologist told her that Maxwell could see, but he wasn’t sure that Maxwell would live. “My first reaction,” Amber said, “was actually defensive and angry because I was at the ophthalmologist. How could he comment on whether my baby would live? I was so confused. Every part of me just wanted to freak out. And I snapped into work mode and started asking questions.” The ophthalmologist explained that with many rare diseases, parents think the problem is with the baby’s eyes when it’s actually a problem with the baby’s brain. “It’s going to be a rare disease,” he said. “There are 7,000 rare diseases. The only way anyone is going to catch this is through genetic testing. Go home and just know that you’re probably going to get really bad news. I want you to know that the majority of people that come in in your shoes don’t make it.” Amber made an appointment with Dr. Austin Larson, a geneticist at Children’s Hospital in Denver who also told Amber, “Something is really wrong. Everything the ophthalmologist said is true.” Dr. Larson had Maxwell’s genome mapped at the Mayo Clinic. It would be four months until they received the results.

SLC6A1

When the phone call came and the people at the Mayo Clinic said they’d clear their calendars for Amber and her husband, she knew it was bad. “We should have taken an Uber,” Amber said. “We should not have driven, but we did. We were shaking when we were led to a bad-news room. The room was full of doctors with super-sad faces, and you just brace for impact, and they said, “Your son has a disease called SLC6A1.” And I had so much adrenaline running already, but I was super confused so I asked, “What’s the name of the disease?” And they said, “It’s SLC6A1.” And I said, “No. That’s the name of a flight number. What’s it called?” And they said, “It’s too rare to have a name. That’s the genetic location.”

“And so my husband and I took out our phones and Googled, and no search results came back. You can’t imagine what it’s like to Google something and not get a search result back. It was devastating. And of course, we’re like, “What does this mean?” And they say, “We don’t know. We have this five-page article from Denmark. We can’t give you a life expectancy. We know he’s going to be super-delayed. These are the things he’s never going to do. He’s going to have a movement disorder like he has Parkinson’s. He’ll probably never be able to play with Riley. And between the ages of three and four, he’s going to develop a really debilitating form of epilepsy. And he’s going to lose all of these skills he fought so hard to gain.” And, they said, “Go home, and give him the best life you can.”

“I’m sure everybody can just feel what it’s like. I think everybody thinks they’ve experienced their lowest moment in life. And we all have, up to this point. And I can just say that there’s not a more low feeling in the entire world than for your perfect little baby to be diagnosed with a disease that has no name and nothing that can be done. The oxygen went out of the room. But I realized I had my entire life to cry and to grieve for myself, but right now, it was not about me. It was about Maxwell.”

As the meeting ended, the doctors were about to refer them to the social workers. Amber wasn’t done. “Absolutely not,” she said. “I have this many doctors in one room. You tell me what to do in the next week, and then I’m going to call you back in one month. And I’m going to figure this out myself.” When she asked what they would do if it were their son, they said they would start calling scientists right away. Amber and her husband left the meeting and stopped by Amber’s office where she told them something horrible had happened and she needed to quit.

Fighting Like a Mother

Since that day, Amber has founded SLC6A1 Connect as a patient organization for families with children who have the same rare disorder as Maxwell. She has called more than 650 scientists – reaching Asia and Australia at night, Europe in the early morning, and the US during the day. She’s read textbooks and journal articles and quizzed doctors.

Along the way, Amber discovered that SLC6A1 is not so rare. It was identified in 2015 and made the testing panels in 2017. She learned that it could be a contributing cause of autism, some types of epilepsy, schizophrenia, bipolar disorder, and ADHD. But Amber needed more than what she could find through her own research. At the end of each call, she’d say, “While we’re on the phone, so you don’t forget, can you introduce me to three people who might be able to help?” She didn’t hang up until the emails reached her.

After identifying one scientist who could help her, Amber flew, unannounced, to a conference where he would be speaking. She sat down next to him. Once she was seated, she wasn’t sure how to begin.

The result of all of this effort? Maxwell could likely be cured with a single treatment that would last about two hours. “All” Amber needed was a genomic mouse and several million dollars. “That’s a ridiculous amount of money that a group of trailblazing parents like myself have to raise now,” says Amber. “But for the people who come after us, it will just be so much easier.”

Two months ago, after hearing Jeff Galvin, CEO of AGT, speak on a podcast for the Center for Advancing Innovation, Amber called to see if he could help. Jeff made time for her several times, to hear her story and to suggest people who might be able to help. One of the people Jeff introduced Amber to was Frances Lefcort, scientific advisor to AGT. Lefcort then introduced Amber to a researcher who was unknown to Amber – a researcher who was an expert in SLC6A1. It was he who suggested Amber pursue an RNA approach, rather than a DNA approach. Says Amber, “This man was so familiar with the gene, he’s like, ‘Well, could you get me a sample soon? Because I could start testing all of those right away.” Today, it looks as if they’ll have something for Maxwell really soon, and it’s all because of Jeff. “He was truly a guardian angel for Maxwell,” said Amber.

Amber has raised the funds necessary for the first rounds of development and testing. With the probable cure in the works, additional funds are being raised at MilestonesforMaxwell. The First Annual Milestones for Maxwell Golf Tournament will be held in Denver on August 17th, with coverage by Fox Sports. Amber continues to fight like a mother as the race for the rest of the funds needed for Maxwell’s treatment continues.

Published on AGT

The Harvard Business Review (HBR) has provided thought-provoking content since 1922. Whether business leaders are interested in optimizing their organizational structure or instituting programs to retain key employees, the HBR provides insights from experts in their fields. In order to achieve success in the emerging biotech industry, biotech leaders must be able to communicate their vision for this entirely new way of producing goods and cures. These top five HBR articles are must-reads that will shape future biotech leaders as they attain the core competencies they will require.

1. What Makes a Leader

In this article, psychologist Daniel Goleman discusses the difference between a leader and a great leader. While intelligence and technical ability are necessary for all leaders, great leaders display a high level of what Goleman calls “emotional intelligence.” The five factors that make up emotional intelligence – self-awareness, self-regulation, motivation, empathy, and social skill – make it possible for highly effective leaders to bring their organizations or teams to higher levels of achievement.

Goleman points out that improvement in all areas is possible, and improvement in any single area has the potential to improve overall emotional intelligence in an individual.

2. What Makes an Effective Executive

Over his 65-year consulting career, Peter Drucker aka “the father of management thinking,” found that effective leaders shared the same eight practices. In this article, Drucker examines the practical applications and implications that occur when executives take the time to:

ask, “What needs to be done?”
ask, “What is right for the enterprise?”
develop action plans.
take responsibility for decisions.
take responsibility for communicating.
focus on opportunities rather than problems.
run productive meetings.
think and say “we” rather than “I.”

3. The Authenticity Paradox

Sooner or later we all have the feeling that the Emperor is not wearing any clothes – that we are not really all we are thought to be. This feeling of inauthenticity is most likely to occur during transitions in our careers, i.e., when we can least afford it. In this article, Dr. Herminia Ibarra, a professor and Chair of Organizational Behavior at the London Business School, discusses the meaning of authenticity, the reason leaders struggle with authenticity as they move outside of their comfort zone, and the ways they can use this feeling as the impetus to achieve personal and professional growth.

4. Why Should Anyone Be Led by You?

Feeling authentic is one thing, answering the question of why anyone should want to be led by you is another. Authors Robert Goffee and Gareth Jones, Europe’s leading experts on organizational culture, leadership, and change posed this question to executives at dozens of companies in Europe and the United States over a ten-year period. They report that the reply was invariably a resounding hush. While the leaders themselves may not have had the answer to this question, Goffee and Gareth identified four unexpected qualities that all inspirational leaders share. These leaders expose some vulnerability, collect and interpret soft data that helps them determine when and how to act, empathize passionately and realistically, and capitalize on what’s unique about themselves. This article provides examples and takeaways from putting these qualities in action.

5. What Leaders Really Do

You may intuit that management and leadership are not the same, but can you articulate the difference? Can you explain why it matters? In this article, John P. Kotter of Harvard does just that in an article that expands upon the insights gained since publication of a 1977 article by Harvard Business School Professor Abraham Zaleznik that was among the first to ask whether or not managers and leaders are different. Bottom line: Leadership is about coping with change. Kotter offers real-world examples of the differences while making the case that while both managers and leaders are essential to a business, the main task for leaders is to move the team or organization in the direction that is good for the enterprise, no matter the circumstances.

You’ll also find “explainers” and other video content on the topic of leadership on the HBR YouTube channel.

Published on AGT

TED Talks began in 1984 as a conference originating in Silicon Valley where powerful voices in Technology, Entertainment, and Design came together to spread potent ideas with broad relevance. Today there are thousands of talks of 18 minutes or less, in more than 100 languages, covering topics ranging from science to global issues. Despite this diversity, all TED talks share a devotion to Ideas Worth Spreading.

In this article, we introduce five TED Talks that explore the progression of innovation that began with mapping the human genome. That essential first step led to an understanding of the possibilities of human DNA and the development of cures and technologies based upon that knowledge. Mapping the genomes of other organisms is proving to be every bit as important to an understanding of the possibilities of their DNA. These five Ted Talks describe recent biotechnology breakthroughs arising from our understanding of genetic material that has given rise to ideas worth spreading, ranging from base pair editing to biofabrication.

How CRISPR lets us edit our DNA

Jennifer Doudna was part of inventing a potentially world-changing genetic technology: the gene-editing technology CRISPR-Cas9.

When Jennifer Doudna and her colleague, Emmanuelle Charpentier, invented CRISPR-Cas9 for editing genomes, it opened the door for scientists to make changes to the DNA in cells – changes that could lead to cures for genetic diseases. By programming the natural process used by Cas9 protein in bacteria to destroy viral DNA, scientists can now delete or insert specific bits of DNA into cells with what Jennifer Doudna describes as “incredible precision.” In her talk, she shares the potential for CRISPR technology and the need for discussion about its ethical implications.

How Creativity Cures

Jeff Galvin shares his work in the growing field of gene therapy and explores the myriad of life-saving and potential life-enhancing uses for this technology.

A revolution is coming to healthcare. This revolution will result in a deluge of “miracle” cures for conditions that are currently untreatable. Galvin explains that humanity will achieve this by reprogramming the “human computer” through the use of the A, G, T, C in our DNA. With the new tools becoming available to gene therapy, Galvin says “the bottom line is that if you can dream it, you can do it.” In this TEDx, Galvin describes the work his company is doing and how gene therapy will change healthcare forever.

Can we cure genetic diseases by rewriting DNA?

David R. Liu leads a research group that combines chemistry and evolutionary techniques to create revolutionary new medicines.

What if we could use CRISPR to alter the single protein responsible for genetic diseases such as the childhood aging disease, progeria? The use of base editors to correct single-point mutations could make this possible by replacing the objectionable protein and “forcing” the appropriate protein to bond with it to form a new base pair. The use of base editors with CRISPR makes the possibility of a real cure for such genetic diseases a reality. In his Talk, David Liu describes the development of base editors and the potential for their use while urging discussion of the ethical obligations inherent in the use of base editors to rewrite DNA.

The medical potential of AI and metabolites

Leila Pirhaji uses artificial intelligence for drug discovery and the treatment of metabolic diseases.

Before we can use our knowledge of the human genome to find treatments for diseases, we must augment the information gained from the genome with information about the activity of the metabolites in our bodies. These small molecules like fat, glucose, and cholesterol play integral parts in the development of diseases such as fatty liver disease. By using AI to analyze the massive amounts of data required for a precise understanding of the patterns for each type of metabolite that connects to underlying disease, we can better develop successful treatments. In her Talk, Leilia Pirhaji recounts the progress that has been made in this effort.

How supercharged plants could slow climate change

Recognized as one of the greatest scientific innovators of our time, Joanne Chory studies the genetic codes of plants. Her goal: to use plants to help fight climate change.

Plants and trees are our natural allies in fighting climate change because the process of photosynthesis takes in CO2 while releasing oxygen and storing carbon in the root system and soil. If we could grow more plants and trees, it would help to combat climate change. Since we can’t take the land currently used or needed in the future for agricultural purposes to accomplish this without creating a severe shortage of food for the growing global population, we need to find a way for agricultural land and crops to do double-duty. In this Talk, Joanne Chory describes the work being done by her team at Salk Institute’s Harnessing Plants Initiative (HPI) to use genetic and genomic techniques to increase the carbon storage capacity of root systems by helping plants grow bigger, more robust root systems. An added benefit? Healthier soil.

Published on AGT

The rapid growth of biopharma is causing a shift to a new paradigm for the drug development and delivery model. In the same manner that the personal computing industry grew and developed business models that fit the way products were sourced, constructed and delivered, a business model for biopharma is taking shape.

Jeff Galvin, CEO of American Gene Technologies (AGT), had 30 years of business and entrepreneurial experience in Silicon Valley during the formative years of the personal computing and internet era. He left retirement as an Angel Investor in real estate and high tech in 2008 to found AGT and lead it in developing a bank for Lentiviral vectors with different characteristics for use with its gene delivery platform.

The use of these vectors with this platform will save time and money in drug development, Galvin said as he shared his vision for the biopharma industry with BioSpace.

The Personal Computing Industry as a Model

In the early days of the personal computing industry, a computer company was responsible for its product from start to finish. This could not only include hardware and software but peripherals as well. As the industry grew and matured, Galvin explained, other industries grew up around the personal computer industry. These were not mere opportunities to outsource; these were companies acting with their own plans and interests in mind. The result of this was the development of software by vendors having no more to do with a computer manufacturer than the ability to code in a language that the computer would recognize.

This autonomy made it possible for companies to specialize in certain types of software, even to the point of supporting one specific app. The need to save data and put new software onto a computer led to an industry based on physical storage media. As computer technology grew, the precise product – floppy to CD and onward – evolved. Over time, it has led to cloud-based computing in which the software no longer comes on a physical medium, says Galvin. This uncoupling of software and peripherals from the computer hardware itself has given rise to exponential growth in applications and the ability to use computers to solve myriad problems.

American Gene Technology (AGT) Offers a Delivery System

Similarly, as the gene and cell therapy industries grow, companies that specialize in one aspect of the drug development process or in one application will be able to focus on that one part. As long as what is developed will work with the human body, genes and cell therapy can be used to alter the DNA. For AGT, this means collaborating with researchers who are looking for a delivery system for the innovative treatments they develop.

Galvin explains, “AGT’s platform is a broad set of reusable components and fundamental innovations on the use of any or all viral vectors to reliably deliver genetic changes to cells that are safe, predictable, and that maintain therapeutic expression for the duration necessary for the “mission” of mitigating the disease state.” The viral vectors are the “diskettes” that carry the “software updates” to your DNA, the “operating system,” of your “organic computer,” aka the human cell. Rather than machines and code, AGT delivery platform makes it possible to use the human body and its genes to treat disease.

AGT began with lentiviruses because, Galvin explains, “it happens to be what we believed was the right vector delivery on our three lead programs of HIV, phenylketonuria (PKU), and cancer. This was because the lentivirus matched the attributes we were looking for in terms of “cargo space for genetic constructs.”

With the ability to deliver the genes needed to modify specific cells types or tissue, AGT is able to provide this capability for a range of therapies. Currently, AGT is working to cure HIV through the use of its lentivirus delivery platform. With a viral vector as the diskette used to load the genetic construct into that vector as the software, the virus will do the work of delivering the critical change to a cell.

The Future

AGT views itself as a “vector agnostic” delivery company, Galvin explained. In the future, they will work with whichever delivery vector is needed. As delivery vectors improve, AGT will have the capability of combining more of their components on a single vector, resulting in the opportunity to address increasingly complex diseases.

“We will look to partners that pioneer new methods of modifying DNA in cells (even CRISPR when it becomes as reliable and safe as lentivirus), and we will continue to revise and optimize our drugs to utilize the capabilities that those partners develop,” Galvin said.

To date, AGT has seen that “each time we start a new drug, we find that our previous R&D yielded components and techniques that provide a base, the starting point, that is up to 80% of the next drug candidate,” Galvin said.

This efficiency is AGT’s strategy for remaining competitive in this disruptive industry. It is also necessary if the benefits of the gene and cell therapy revolution are to achieve the reductions in cost necessary to reach the greatest number of patients in need.

Galvin believes the evolution of the gene and cell therapy technology and industry will track closely with the evolution of the computer industry. His vision is an encouraging one for the rest of us. If the comparison holds, we’ll see that as companies find their place in the industry and hone their offering, the advances to be made will be rapid and significant. The result will be improved treatments, along with treatments for diseases that are currently considered incurable.

Depression affects hundreds of millions of people worldwide. Relmada Therapeutics is working to develop a treatment for those with depression that does not respond to drugs currently on the market.

Relmada Therapeutics is a publicly-traded, specialty pharmaceutical company working at the clinical stage to develop dextromethadone (REL-1017) to treat a number of central nervous system (CNS) disorders. Prior to his work with Relmada, CEO Sergio Traversa, PharmD, MBA, had an impressive career in pharma and health care in the United States and Europe, as well as positions in financial analysis and investment in these areas.

One of Traversa’s earliest introductions to antidepressants was the work he did on the development and marketing of Prozac. He was also involved in the early development of Zyprexa and Cymbalta. More recently, Traversa co-founded Medeor, Inc., a spinoff company from Cornell University that is now Relmada. Traversa recently spoke with BioSpace about the work being done by Relmada to develop REL-1017 as a treatment for those with major depression that does not respond to currently available medications.

A New Approach

Traditional antidepressants such as Prozac, et. al., work on the uptake and modulation of neurotransmitters. This results in increased serotonin, norepinephrine and dopamine activity in the brain. It is this increase in neurotransmitter activity that brings about improvement. However, Traversa explains, it can take several weeks for these types of antidepressants to take effect. Since each specific antidepressant is not equally effective in every individual, it is sometimes necessary to try a number of different medications before one is effective. In some cases, none are effective, and the depression does not respond to treatment.

Dextromethadone (REL-1017) uses a different pathway to treat depression. Rather than working on the uptake and modulation of neurotransmitters, “REL-1017 increases the number of synapses in the brain,” said Traversa. As the number of synapses increases, the communication between them is increased. In preclinical studies conducted at Yale University, this activity ultimately resulted in more efficient communications among brain cells and improved cognition, as well as a rapid onset and longer-term antidepressant benefit in patients.

Clinical Evidence

In a clinical trial, patients who had not been helped by one to three previous antidepressant drugs were given REL-1017 as an adjunct to their existing antidepressant. Within the first four days, a statistically significant and clinically meaningful improvement in the patients’ depression symptoms was observed. These improvements continued for the remainder of the seven-day period that patients received treatment with REL-1017. Additionally, for the seven days following treatment, patients continued to experience improvements even though they had stopped taking REL-1017.

Traversa explains that this is significant because “existing antidepressants, while effective, only work in about one-third to half of the patients, meaning that many of the patients do not really benefit from these drugs. You have at least half, and more than half, of the patients who don’t really respond well or at all to the first treatment course or drug used.” The response of these patients to REL-1017 signals that an effective drug for their depression may be on the horizon.

Not the Only Drug Using this Pathway

Relmada’s REL-1017 will not be the only drug that uses this pathway. J&J has a product already in use, Spravato, that uses this pathway. Their drug has shown rapid-acting and long-lasting antidepressant effect. The major difference between Spravato and Relmada’s drug will be that J&J’s drug uses a nasal spray as the delivery mechanism, Traversa says. This spray is administered twice per week, in a clinical setting. An observation time of two hours is required after the dose. There are also driving restrictions until the day after the treatment. These requirements are in effect because Spravato can cause sedation, blood pressure changes, and dissociative effects in some patients. “The plan for REL-1017,” says Traversa, “is that it will be delivered in the form of a pill taken once a day at home.”

“We believe that REL-1017, if approved, has the potential to change the way depression is treated. This will change the lives of many people,” Traversa said. “We also believe that our proof-of-concept data from our Phase II trial of REL-1017 is very compelling. We are now focused on generating additional clinical data with REL-1017 and moving toward a registration program with the product expected to start at the end of this year.”

For those with major depression that does not respond to the treatments that are currently available, the clinical data indicates that REL-1017 may make a significant difference.

Published on BioSpace

Depression affects hundreds of millions of people worldwide. Relmada Therapeutics is working to develop a treatment for those with depression that does not respond to drugs currently on the market.

A New Approach

Clinical Evidence

Not the Only Drug Using this Pathway

For those with major depression that does not respond to the treatments that are currently available, the clinical data indicates that REL-1017 may make a significant difference.

Published on BioSpace