Raptor drugs command huge potential
Thirst plagued her childhood. When other kids bolted to the playground at recess, Stephanie Trudell sneaked into the bathroom to guzzle water. It brought brief respite. Her unslaked thirst roared back. "I was always thirsty," she said, "always thirsty."
As with many of nearly 7,000 rare diseases caused by genetic flaws, Trudell’s symptoms showed up soon after birth. When she was nine months old, doctors diagnosed incurable nephropathic (infantile) cystinosis. The disease afflicts 500 patients in the United States and 2,000 worldwide, primarily children, and provides a potentially $300 million market for a drug treatment launched in 2013 by Novato based Raptor Pharmaceutical Corp. The company, which sold about $70 million of its cystinosis drug Procysbi in the first year after FDA approval, has 82 employees in Novato and 120 worldwide.
Now 35, Trudell flew from her home in Omaha, Neb., to visit Raptor for Rare Diseases Day at the end of February. Julie Anne Smith, who took over Raptor’s reins as CEO and president in January, celebrated Trudell and other patients the company’s raison d’tre.
Beyond thirst, cystinosis causes another unpleasant symptom, Trudell said: eye crystals, which cause irritation and blur, especially in bright sun. "It looks like shattered glass," Trudell said. "Sunlight made my eyes burn. I can’t see when it’s bright out, when it’s night." She has bifocals "and it’s still hard," she said.
Cystinosis caused by errant CTNS genes on the 17p13 chromosome appears when amino acid cystine goes into cells then cannot escape. Cells overloaded with cystine crystallize and die usually cells in the kidneys, liver, eyes, muscles, white blood cells and central nervous system. Cystinosis also delays a child’s growth.
Cystinosis was treatable when Trudell was a child: the drug Cystagon, or cysteamine bitartrate, breaks down cystine, has to be taken every six hours and causes severe nausea as well as awful body odor like rotten eggs. Cystagon, initially a liquid then in capsule form, costs about $8,000 a year, but its side effects prompt many patients to balk. "Cystagon is terrible. It made me sick to my stomach," Trudell said.
"I used to stash and hide my meds. It was so gross," she said. "I would put it in a baggie under my mattress, in my dresser drawer." Her kidneys failed at age 14, leading to a transplant from her
cheap ray bans mother in 1993, hemodialysis then a second kidney transplant in 2006 after she stopped taking Cystagon. "Dialysis really sucks," she said. "I had a poor attitude. I was living, but I wasn’t really living."
Trudell started taking Raptor’s Procysbi in November 2014. "I can take it," she said. "I’m not sick. It changed my life."
Raptor scientists found an ingenious way to reformulate cysteamine bitartrate molecules and deliver them with delayed release directly to the intestine, bypassing the stomach and curbing nausea. "What was novel," CEO Smith said, "was recognition that if you delivered it to
replica ray ban sunglasses the duodenum (small intestine), bioavailability was improved. The specific way we coated the microbeads gave us continuous levels of therapeutic" cysteamine bitartrate despite lower quantities of the drug.
Procysbi, which costs $250,000 a year, radically changed Trudell’s life and caused few side effects. "Oh my gosh. It makes me feel better," she said, "makes me want to get up out of bed." Trudell lives on Social Security disability income; medical bills are covered by government programs. Persistent thirst remains. The drug reduced crystals in her eyes.
This year holds big potential for Raptor beyond Procysbi, according to Smith, who assumed leadership of Raptor from co founder Christopher Starr. The company’s name derived originally from work on receptor associated proteins (RAP), but the focus shifted.
"He is one of the unsung biotech pioneers," Smith said. Starr co founded BioMarin, located in San Rafael, and was the primary founder of Raptor. "He is a discovery and development guy. Once the business turns commercial," he hankers for more science, she said. Starr still consults with Raptor on science and sits on its board.
Procysbi provides "really nice momentum on our revenue," Smith said, and could rise to $90 million in 2015. On Feb. 26, the company reported fourth quarter 2014 revenue of $17.3 million. Annual revenue was nearly $70 million, up from $17 million in 2013. The company, which went public in 2003, had net losses of $52.5 million for 2014, and accumulated deficit of $258 million.
A small fraction of Procysbi revenue comes from sales in Europe. "People are afraid of Europe," she said. "It’s tougher," and difficult to govern business from afar.
Raptor could ultimately reap annual revenue of nearly $250 million from sales of Procysbi, she said. "The range is $150 million to $300 million if you make reasonable assumptions about product market penetration," she said. Patients in many countries could not afford the drug. market exclusivity for cystinosis for 7.5 years under the Orphan Drug Act of 1983 and the Rare Diseases Act of 2002. "The Orphan Drug Act was essential to provide incentives to companies to develop and invest in" drugs for rare diseases, Smith said.
A Raptor drug called RP103 also a formulation of cysteamine bitartrate holds promise in treating several diseases. "What we’re excited about is RP103′s potential" in these other therapeutic areas that have much larger markets, Smith said.
Raptor is conducting RP103 clinical trials with Huntington’s Disease, a neural degeneration, with a potential market of
replica ray bans about 70,000 patients in the United States and Europe, and 100,000 worldwide.
In conjunction with the National Institutes of Health, Raptor has phase two clinical trials of RP103 for treating pediatric non alcoholic fatty liver disease, which can lead to liver failure. Nearly a third of Americans, roughly 100 million people, have the disease, which affects some 15 percent of American children. Non alcoholic steatohepatitis (NASH), an aggressive form of non alcoholic fatty liver disease, causes degeneration of fat in the liver. Raptor clinical trials focus on children with NASH. Many other biotech companies are pursuing treatment for adults with NASH.
"NASH is occurring in people at younger and younger ages," Smith said. "This is scary. In western countries, the prevalence of fatty livers in kids of all weights is 9 to 10 percent. It’s astounding.
"Kids who have NASH, their livers are more susceptible," Smith said. Such patients may later develop life threatening hepatitis cirrhosis. "They will require a liver transplant in their lifetime. It’s one of the highest unmet medical needs," she said. Adults with NASH typically die of other causes before their livers fail.
An inventor on one of Raptor’s patents is a pediatric hepatologist who was treating NASH patients and had one die at age 13. The disease has few symptoms, Smith said, such as upper abdominal pain. NASH occurs even in children who are not overweight. "It appears to be a lifestyle thing," she said, "a television disease" affecting couch potatoes. "The liver is barraged with fatty acids. The continuous insult eventually overcomes the cells," she said, and the inflamed liver cannot recover.
The market for RP103 in pediatric NASH is 500,000 to 1.5 million in the United States, she said. "It’s a large market," she said, but few are diagnosed until the kids are in an advanced stage. Sometimes children are diagnosed when a routine lab test shows massively elevated liver enzymes. A Raptor clinical trial involving 169 patients is underway; patients concluded 12 months of treatment in January and will have a follow up biopsy. Those results are expected by the end of 2015.
Because it’s not an orphan condition (fewer than 200,000), the FDA will likely require further trials, she said. "Before we see the data, it’s impossible to talk about price," she said. "Price needs to be a reflection of the value of that therapy for those patients," she said.
Mitochondrial disease, a genetic flaw
cheap ray ban outlet that impedes cells’ ability to make energy, also may be treated by RP103.
"We’re going after fundamental cellular processes," Smith said of the research. "RP103 offers us a treasure trove of potential biologic actions that we can use to target specific diseases," including disorders involving protein misfolding, fibrosis (excessive fibrous tissue), and mitochondrial stress and dysfunction. "That’s a huge number," she said, "all open to us as potential" applications of RP103, which may slow progression of metabolic decline.
Co founder Starr, her predecessor CEO, worked with the academic research community in early development of RP103. "That was his baby," Smith said. "It was ingenious to recognize the potential broad application." The company owns patents that protect various aspects of RP103 formulation as well as methods of use.Articles Connexes：