Category Archives: INDICATIONS

CRISPR Tech for Eye Disease Moves Closer to Reality

A study published in the journal of the American Academy of Ophthalmology shows that a CRISPR-based treatment can restore retinal function in mice.

Researchers from Columbia University have developed a new technique for the powerful gene editing tool CRISPR to restore retinal function in mice afflicted by a degenerative retinal disease, retinitis pigmentosa. This is the first time researchers have successfully applied CRISPR technology to a type of inherited disease known as a dominant disorder. This same tool might work in hundreds of diseases, including Huntington’s disease, Marfan syndrome, and corneal dystrophies. Their study was published online today in Ophthalmology, the journal of the American Academy of Ophthalmology.

Stephen H. Tsang, M.D., Ph.D., and his colleagues sought to create a more agile CRISPR tool so it can treat more patients, regardless of their individual genetic profile. Dr. Tsang calls the technique genome surgery because it cuts out the bad gene and replaces it with a normal, functioning gene. Dr. Tsang said he expects human trials to begin in three years. “Genome surgery is coming,” Dr. Tsang said. “Ophthalmology will be the first to see genome surgery before the rest of medicine.”

Retinitis pigmentosa is a group of rare inherited genetic disorders caused by one of more than 70 genes. It involves the breakdown and loss of cells in the retina, the light sensitive tissue that lines the back of the eye. It typically strikes in childhood and progresses slowly, affecting peripheral vision and the ability to see at night. Most will lose much of their sight by early adulthood and become legally blind by age 40. There is no cure. It is estimated to affect roughly 1 in 4,000 people worldwide.

Since it was introduced in 2012, the gene editing technology known as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) has revolutionized the speed and scope with which scientists can modify the DNA of living cells. Scientists have used it on a wide range of applications, from engineering plants (seedless tomatoes) to producing animals (extra lean piglets). But as incredible as genome surgery is, CRISPR has some flaws to overcome before it can live up to its hype of curing disease in humans by simply cutting out bad genes and sewing in good ones.

Typically, CRISPR researchers design a short sequence of code called guide RNA that matches the bit they want to replace. They attach the guide RNA to a protein called Cas9, and together they roam the cell’s nucleus until they find a matching piece of DNA. Cas9 unzips the DNA and pushes in the guide RNA. It then snips out the bad code and coaxes the cell to accept the good code, using the cell’s natural gene repair machinery.

Diseases like autosomal dominant retinitis pigmentosa present a special challenge to researchers. In autosomal dominant disorders, the person inherits only one copy of a mutated gene from their parents and one normal gene on a pair of autosomal chromosomes. So, the challenge for CRISPR-wielding scientists is to edit only the mutant copy without altering the healthy one. In contrast, people with autosomal recessive disorders inherit two copies of the mutant gene. When two copies of the gene are mutated, treatment involves a more straightforward, one-step approach of simply replacing the defective gene. Dr. Tsang and colleagues have come up with a better strategy to treat autosomal dominant disease. It allowed them to cut out the old gene and replace it with a good gene, without affecting its normal function.

Instead of using one guide RNA, Dr. Tsang designed two guide RNAs to treat autosomal dominant retinitis pigmentosa caused by variations in the rhodopsin gene. Rhodopsin is an important therapeutic target because mutations in it cause about 30 percent of autosomal dominant retinitis pigmentosa and 15 percent of all inherited retinal dystrophies.

This technique allowed for a larger deletion of genetic code that permanently destroyed the targeted gene. Dr. Tsang found that using two guide RNAs instead of one increased the chance of disrupting the bad gene from 30 percent to 90 percent. They combined this genome surgery tool with a gene replacement technique using an adeno-associated virus to carry a healthy version of the gene into the retina. Another advantage is that this technique can be used in non-dividing cells, which means that it could enable gene therapies that focus on nondividing adult cells, such as cells of the eye, brain, or heart. Up until now, CRISPR has been applied more efficiently in dividing cells than non-dividing cells.

Dr. Tsang used an objective vision test to evaluate the mice after treatment to show a significant improvement in retinal function. An electroretinogram is typically used to evaluate retinal health in humans. It tests the health of the retina much like an electrocardiogram (EKG) tests the health of the heart. Previous CRISPR studies for retinal diseases have relied on a less objective measure that involves evaluating how often the mouse turns its head in the direction of a light source. Dr. Tsang used electroretinography to show that retinal degeneration slowed in treated eyes compared with untreated eyes.

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Orphan Drug Designation for Treatment of ALS – Amyotrophic Lateral Sclerosis

On March 29, 2018 the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development granted Orphan Drug Designation (ODD) to experimental therapeutic EH301 for the treatment of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease.

The Orphan Drug Designation submission included data from a 2017 double-blind placebo-controlled European pilot study in humans. To expand on the results of the pilot study, Elysium Health expects to initiate a placebo-controlled study in collaboration with Mayo Clinic to evaluate EH301 in up to 150 adults with ALS by the fourth quarter of 2018. The granting of ODD to EH301 does not alter the standard regulatory requirement through adequate and well-controlled studies to support FDA approval, and there is no guarantee EH301 will be approved for the treatment of ALS by FDA.

Elysium Health Chief Scientist Dr. Leonard Guarente remarked that “There is a great deal of work to be done to address the need for continued research to better understand and to treat all neurodegenerative diseases. We believe that the FDA’s granting of Orphan Drug Designation for EH301 for ALS underscores the need for novel treatments for this rare condition.”

ALS is a rare neurodegenerative disease that affects nerve cells that control voluntary muscles throughout the body to produce movements including talking, eating, walking, and breathing. ALS is progressive, meaning it gets worse over time. As the nerves lose the ability to control muscles, the muscles become weak and eventually lead to paralysis. Most people with ALS succumb to respiratory failure, usually within three to five years from when symptoms first appear. Please visit the ALS website for more information.

The FDA’s ODD program provides orphan status to drugs intended for the safe and effective treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. It is estimated that there are approximately 15,000-20,000 Americans with ALS. Please see the NIH ALS Fact Sheet for details.

Additional information can be found on the Christopher & Dana Reeve Foundation website regarding current therapies and disease trends.

Disclosure: Mayo Clinic has a financial interest in Elysium Health. All revenue Mayo Clinic receives will be used to fund its not-for-profit mission in medical research and education.

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Beneficial Skin Bacteria Protect Against Skin Cancer

Science continues to peel away layers of the skin microbiome to reveal its protective properties.  Researchers now report on a potential new role for some bacteria on the skin: protecting against cancer.

“We have identified a strain of Staphylococcus epidermidis, common on healthy human skin, that exerts a selective ability to inhibit the growth of some cancers,” said Richard Gallo, MD, PhD, Distinguished Professor and chair of the Department of Dermatology at UC San Diego School of Medicine. “This unique strain of skin bacteria produces a chemical that kills several types of cancer cells but does not appear to be toxic to normal cells.”

The team discovered the S. epidermidis strain produces the chemical compound 6-N-hydroxyaminopurine (6-HAP). Mice with S. epidermidis on their skin that did not make 6-HAP had many skin tumors after being exposed to cancer-causing ultraviolet rays (UV), but mice with the S. epidermidis strain producing 6-HAP did not.  6-HAP is a molecule that impairs the creation of DNA, known as DNA synthesis, and prevents the spread of transformed tumor cells as well as the potential to suppress development of UV-induced skin tumors.

Mice that received intravenous injections of 6-HAP every 48 hours over a two-week period experienced no apparent toxic effects, but when transplanted with melanoma cells, their tumor size was suppressed by more than 50 percent compared to controls.

“There is increasing evidence that the skin microbiome is an important element of human health. In fact, we previously reported that some bacteria on our skin produce antimicrobial peptides that defend against pathogenic bacteria such as, Staph aureus,” said Gallo.

In the case of S. epidermidis, it appears to also be adding a layer of protection against some forms of cancer, said Gallo. Further studies are needed to understand how 6-HAP is produced, if it can be used for prevention of cancer or if loss of 6-HAP increases cancer risk, said Gallo.

More than 1 million cases of skin cancer are diagnosed in the United States each year. More than 95 percent of these are non-melanoma skin cancer, which is typically caused by overexposure to the sun’s UV rays. Melanoma is the most serious form of skin cancer that starts in the pigment-producing skin cells, called melanocytes.

Displayed with permission from FARS News Agency via RePubHub

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Huntington’s Disease Molecule Can Kill Cancer Cells

Scientists have destroyed numerous types of human cancer cells with a toxic molecule characteristic of fatal genetic illness Huntington’s disease.

The researchers hailed the molecule—which has killed both human and mouse ovarian, breast, prostate, liver, brain, lung, skin and colon cancer cell lines in mice—as a “super assassin.” Their results were published in the journal EMBO Reports.

Huntington’s disease is a progressive illness caused by an excess of a specific repeating RNA sequence in the Huntington gene, which is present in every cell. The defect causes the death of brain cells, and gradually worsens a person’s physical and mental abilities. The disease has no cure.

Researchers believe that the defect may be even more powerful against cancer cells than nerve cells in the brain, and the team hopes it can be harnessed to kill cancer cells without causing Huntington’s symptoms.  “This molecule is a super assassin against all tumor cells,” said senior author Marcus Peter, a professor of cancer metabolism at Northwestern University Feinberg School of Medicine, Chicago, in a press statement. “We’ve never seen anything this powerful.”

Peter collaborated with Feinberg colleague Shad Thaxton, associate professor of urology, to deliver the molecule in the form of nanoparticles to mice with human ovarian cancer. The targeted molecule decreased tumor growth with no toxicity to the mice.

First author Andrea Murmann, a research assistant professor who discovered the cancer-killing mechanism, used the molecule to kill numerous other human and mouse cancer cell lines. Building on previous research into a cancer “kill switch”, Murmann looked to diseases associated with low rates of cancer and a suspected RNA link.  “I thought maybe there is a situation where this kill switch is overactive in certain people, and where it could cause loss of tissues,” Murmann said in the statement. “These patients would not only have a disease with an RNA component, but they also had to have less cancer.“

There is up to 80 percent less cancer in people with Huntington’s disease than the general population.  Murmann recognised similarities between the kill switch and the toxic Huntington’s disease RNA sequences.  Based on their results, the team believe the “super assassin” molecule could be used to fight cancer in humans. “We believe a short-term treatment cancer therapy for a few weeks might be possible, where we could treat a patient to kill the cancer cells without causing the neurological issues that Huntington’s patients suffer from,” Peter said.  The scientists next aim to refine the molecule’s delivery method to improve tumor targeting, and to stabilize the nanoparticles for storage.

By Katherine Hignett – Displayed with permission from Newsweek via RePubHub License; Cancer Cells courtesy of PixaBay FREE LIC CC0 

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ABRCC Consortia MD Elena Shagisultanova Targets Treatment-Resistant Breast Cancer

Metastatic triple-positive breast cancer frequently resists treatments. Scientists at the University of Colorado Cancer Center are testing a unique combination of medications to change that.

Growth of breast cancer cells is often propelled by one of three receptors – estrogen receptors (ER), progesterone receptors (PR) or the growth factor receptor called HER2. Treatments exist targeting each of these receptors individually. However, when all three receptors are present – this “triple-positive” breast cancer – blocking any single receptor is not enough.  Treatments that block hormonal (estrogen and progesterone) receptors may be not very effective because tumor cells may use HER2 receptor to grow. The drugs that block HER2 receptors may not work as well because the cells will use hormonal receptors to survive. Chemotherapy works against triple-positive breast cancers, however, it has multiple side effects. Previous clinical trials have been largely unsuccessful in defining a well-tolerated targeted drug combination that blocks all avenues for growth of triple-positive breast tumors.

“Under the current guidelines, patients with triple-positive metastatic breast cancer have two options as a first line of treatment and neither is a great option,” says Elena Shagisultanova, MD, PhD, investigator at the CU Cancer Center and assistant professor in the University of Colorado School of Medicine’s Division of Medical Oncology. “One approach is to start an anti-hormonal pill, which is generally non-toxic. However, the response usually lasts only three to four months. The other choice is to start chemotherapy combined with HER-2 targeted agents. This option is effective, but it has multiple side effects.”

Shagisultanova is the principal investigator on the multi-institutional trial.  It is also an investigator-initiated trial which allows physician/scientists to test treatments that their hands-on experience in the lab and clinic indicate may offer meaningful results. Shagisultanova believes she and CU Cancer Center colleagues may have another option: a regimen using three pills, each targeting a different pathway of the disease. The trial combines tucatinib, which inhibits HER2, with letrozole targeting hormone receptors, and the CDK4/6 inhibitor palbociclib.

“We think hormone receptor and HER-2 signals are coming together to help cancer cells resist treatment,” says Shagisultanova. “The CDK4/6 inhibitor palbociclib can block these converging signals in the nucleus. We believe that if we can inhibit the signaling deeper in the tumor cell using this triple blockade, patients will have longer lives and better quality of life.”  Tucatinib, palbociclib and letrozole tend to have different side-effects, leading Shagisultanova to believe the triple combination of targeted agents will be well- tolerated.

Early clinical trials often exclude patients whose cancer has already metastasized to the brain, in large part due to the inability of anti-cancer drugs to penetrate the blood-brain barrier to reach the disease in the central nervous system. However, because tucatinib has proven effective in shrinking HER2-positive breast tumors that have spread to the brain, patients with brain metastases are, in fact, included in the current trial.

“Metastatic disease in the brain is one of the most dangerous complications of triple-positive breast cancer. If we can prevent development of brain metastases, or effectively treat metastatic disease in the brain, it will improve the lives of many patients,” Shagisultanova says.  “There are many challenges in designing and delivering clinical trials,” says Christopher Lieu, MD, CU Cancer Center’s deputy associate director for clinical research. Lieu also leads CU Cancer Center’s efforts in further developing an Investigator-Initiated Trials Committee.

“We are fortunate at CU Cancer Center to have innovative clinicians who are analyzing data to find novel and innovative strategies to target malignancies that are in serious need of better therapies,” Lieu adds.  “Trials like this one are critical in moving cancer science forward and finding effective, non-toxic therapies.”

This trial is currently open for enrollment at the ABRCC Consortia Academic sites of: University of Colorado Cancer Center, Northwestern University, Chicago, IL; University of Texas Health and Science Center in San Antonio, TX; Stony Brook University, NY; University of Arizona, Tucson, AZ, and University of New Mexico, Albuquerque, NM.

The trial is funded by the Pfizer ASPIRE Award in Breast Cancer Research. Cascadian Therapeutics and Pfizer are providing the study drugs tucatinib and palbociclib.

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Cancer Deaths Decline Again in US

Death rates from cancer in the United States dropped again between 2014 and 2015, continuing a downward trend that began in 1991 and has meant 2.4 million fewer deaths.

Advances in early detection and treatment, along with a drop in smoking, are believed to be responsible for much of the 26 percent drop since 1991, said the findings in the American Cancer Society’s comprehensive annual report. “This new report reiterates where cancer control efforts have worked, particularly the impact of tobacco control,” said Otis W. Brawley, chief medical officer of the American Cancer Society.

“A decline in consumption of cigarettes is credited with being the most important factor in the drop in cancer death rates.”  However, he noted that “tobacco remains by far the leading cause of cancer deaths today, responsible for nearly three in 10 cancer deaths.”

Overall, the US cancer death rate reached a peak of 215.1 per 100,000 population in 1991, and has declined to 158.6 per 100,000 in 2015.

Deaths from lung cancer made a 45 percent decline among men and 19 percent among women.  Cancers of the breast, prostate and colon and rectum are also down steeply. The report forecasts about 1.7 million new cancer cases and 609,640 cancer deaths in the United States in 2018. “Over the past decade, the overall cancer incidence rate was stable in women and declined by about two percent per year in men,” it said.

While progress is evident, stark racial disparities remain. The cancer death rate in 2015 was 14 percent higher in blacks than in whites, down from a peak of 33 percent in 1993.

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Displayed with permission from AFP, usage courtesy of RePubHub license; Image courtesy of Pixabay by alisea_30 under CC0 License.

AI-Driven Discovery of Novel Predictors of Parkinson’s

The discovery was powered by patient data from the Parkinson’s Progression Markers Initiative, sponsored by the Michael J. Fox Foundation for Parkinson’s Research.

GNS Healthcare (GNS), a leading precision medicine company, announced the discovery of genetic and molecular markers of faster motor progression of Parkinson’s Disease (PD) patients, the LINGO2 gene together with a second genetic variant, along with demographic factors.

The publication describing the discovery, titled “Large-scale identification of clinical and genetic predictors of Parkinson’s disease motor progression in newly-diagnosed patients: a longitudinal cohort study and validation,” appears in the journal The Lancet Neurology. This discovery may accelerate the development of new drugs and better match new drugs to individual patients.

“Being able to use these predictors in the clinical setting will lead to faster and significantly cheaper clinical trials and accelerate the availability of new Parkinson’s Disease drugs for patients in need,” said Colin Hill, Chairman, CEO, and co-founder of GNS Healthcare. “A major hurdle in Parkinson’s research is that rates of progression are extremely varied. Some patients progress very quickly while others do not. With accurate predictors of rates of progression, we will be able to remove uncertainties from drug development and patient response, reduce the number of clinical trial enrollees required by as much as twenty percent, and speed up the development of effective new drugs.”

REFS™, the GNS causal machine learning (ML) and simulation platform was used to transform the longitudinal genetic and clinical patient data from 429 individuals (312 PD patients and 117 controls) into computer models that connect the genetic and molecular variation of patients to motor progression rates. These computer models were used to simulate the future effects of the genetic and prognostic variables on motor outcomes, essentially predicting the motor progression rate for each patient. The models were validated in an independent longitudinal study, and clearly demonstrated the ability to prospectively differentiate between patient progression rates.

“There is still so much to understand about the progression of chronic, debilitating illnesses like Parkinson’s disease,” said Jeanne C. Latourelle, D.Sc., a co-author of the study and Director of Precision Medicine, GNS Healthcare. “The validation of our models in this study underscores the power of our REFS™ technology and its ability to accelerate the development of effective therapies for patients in need.”

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New Report: Breast Cancer Fatalities Plummet 40%

The American Cancer Society says women face a one-in-eight chance of getting breast cancer and more than 40,600 will succumb this year in the U.S. from the disease.

But improved treatments and early detection are producing promising results, because fatalities from the cancer have dropped almost 40 percent between 1989 and 2015.  That, according to a new report released by ACS, saved some 322,600 lives.  While breast cancer rates increased from 1975 to 1989, the study notes, the fatality rates have dramatically decreased, dropping an actual 39 percent over that period.

The results confirm a steady downward trend over recent years.  Advances in chemotherapy regimens that were developed in the 1980s, the introduction of new drugs like tamoxifen and Herceptin, and early detection through mammograms have reduced the likelihood of breast cancer patients dying from the disease, the report notes.

Breast cancer is the most common cancer diagnosed among U.S. women and is the second leading cause of cancer death among women after lung cancer, according to ACS.  The American Cancer Society publishes the “Breast Cancer Statistics” report every two years to track the latest trends in breast cancer incidence, mortality, survival and screening by race/ethnicity in the United States, as well as state variations in these measures.

The report reveals that black women continue to have higher breast cancer death rates than whites nationally. “Non-Hispanic white and non-Hispanic black women have higher breast cancer incidence and death rates than women of other race/ethnicities; Asian/Pacific Islander (API) women have the lowest incidence and death rates,” the report states. “Although the overall breast cancer incidence rate during 2010 through 2014 was slightly lower in non-Hispanic black women than in non-Hispanic white, the breast cancer death rate during 2011 through 2015 was 42 percent higher in NHB women than in NHW women.”

The report also links the physiology of black and white women to the discrepancy, noting that black women do not benefit from the development of tamoxifen because they are less inclined to have the type of breast cancer known as “estrogen-receptor positive” that the drug alleviates.  In addition, black women are twice as likely as white women to develop “triple negative breast cancer,” which can be more difficult to treat, the report noted.

But the black-white disparity is stabilizing.  There were no significant differences in breast cancer death rates between black and white women in seven states, according to the study, while Massachusetts, Connecticut, and Delaware had similar rates, suggesting equitable breast cancer outcomes are feasible.

“A large body of research suggests that the black-white breast cancer disparity results from a complex interaction of biologic and nonbiologic factors, including differences in stage at diagnosis, tumor characteristics, obesity, other health issues, as well as tumor characteristics, particularly a higher rate of triple negative cancer,” lead author of the report, Carol DeSantis said.  “But the substantial geographic variation in breast cancer death rates,” she continued, “confirms the role of social and structural factors, and the closing disparity in several states indicates that increasing access to health care to low-income populations can further progress the elimination of breast cancer disparities.”

By Alicia Powe, Displayed with permission from WND via RePubHub; Chart Courtesy of Nat’l Center for Health Statistics/CDC

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Vaccine for Meningitis Shows Some Protection Against Gonorrhea

Scientists have not been able to develop a vaccine against the sexually transmitted disease gonorrhea, despite working toward one for more than 100 years.  However, they may have stumbled onto something that could provide clues to advance the development of such a vaccine.

Decades ago, in the late 1990s, a strain of meningitis B was reaching epidemic proportions in New Zealand. A vaccine, MeNZB, was developed to protect young people who were at the highest risk of getting this particular type. It did not provide protection against any other strain.

Between 2004 and 2006, MeNZB was given to anyone under the age of 20. Babies and preschoolers were routinely immunized until 2008. People with a high medical risk continued to get the vaccine until 2011. Once the epidemic was over, the vaccination program was stopped.

However, scientists noticed that the meningitis vaccine also seemed to offer some protection against gonorrhea. A study published in the Lancet last month showed that one-third of the people who had received MeNZB did not get gonorrhea, compared to a control group who was not inoculated. The lead author noted that the bacteria causing both diseases share between 80 and 90 percent of their primary genetic sequences.

Dr. Steven Black, an infectious disease expert at Cincinnati Children’s Hospital, noted, “This is the first time it’s been shown that you could have a vaccine that would protect against gonorrhea. And if these results are confirmed in another setting, that would mean that it would be very reasonable … to go forward with developing perhaps a more targeted vaccine.” Black’s comments were published in the current issue of JAMA, the Journal of the American Medical Association.  The JAMA article concludes that ultimately, a preventive vaccine could be the only sustainable solution to a fast-changing bug that has proven adept at developing resistance.

The World Health Organization reports that gonorrhea is becoming harder, and sometimes impossible, to treat, warning that it could become incurable in the not-too-distant future. At the moment, there no new antibiotics being developed to treat this disease.

The U.S. CDC reports that gonorrhea is the second most commonly reported notifiable disease in the United States. All known cases must be reported to the CDC, but officials there estimate that they are notified of fewer than half of the 800,000 new cases each year.

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First FDA Approval for Sickle Cell Treatment in Nearly 20 Years

The U.S. Food and Drug Administration approved Endari (L-glutamine oral powder) for patients age five years and older with sickle cell disease to reduce severe complications associated with the blood disorder.  The FDA granted the approval of Endari to Emmaus Medical Inc.

“Endari is the first treatment approved for patients with sickle cell disease in almost 20 years,” said Richard Pazdur, M.D., acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “Until now, only one other drug was approved for patients living with this serious, debilitating condition.”

Sickle cell disease is an inherited blood disorder in which the red blood cells are abnormally shaped (in a crescent, or “sickle,” shape). This restricts the flow in blood vessels and limits oxygen delivery to the body’s tissues, leading to severe pain and organ damage. According to the National Institutes of Health, approximately 100,000 people in the United States have sickle cell disease. The disease occurs most often in African-Americans, Latinos and other minority groups. The average life expectancy for patients with sickle cell disease in the United States is approximately 40 to 60 years.

The safety and efficacy of Endari were studied in a randomized trial of patients ages five to 58 years old with sickle cell disease who had two or more painful crises within the 12 months prior to enrollment in the trial. Patients were assigned randomly to treatment with Endari or placebo, and the effect of treatment was evaluated over 48 weeks. Patients who were treated with Endari experienced fewer hospital visits for pain treated with a parenterally administered narcotic or ketorolac (sickle cell crises), on average, compared to patients who received a placebo (median 3 vs. median 4), fewer hospitalizations for sickle cell pain (median 2 vs. median 3), and fewer days in the hospital (median 6.5 days vs. median 11 days).  Patients who received Endari also had fewer occurrences of acute chest syndrome (a life-threatening complication of sickle cell disease) compared with patients who received a placebo (8.6 percent vs. 23.1 percent).

Endari received Orphan Drug designation for this use, which provides incentives to assist and encourage the development of drugs for rare diseases.  In addition, development of this drug was in part supported by the FDA Orphan Products Grants Program, which provides grants for clinical studies on safety and/or effectiveness of products for use in rare diseases or conditions.

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