Orphan Drug NDA Approval for Protalix Biotherapeutics, Israel

 

Target Health congratulates our friends and colleagues at Protalix Biotherapeutics for FDA approval of Elelyso (taliglucerase alfa) for long-term enzyme replacement therapy to treat Gaucher disease. Gaucher disease occurs in people who do not produce enough of an enzyme called glucocerebrosidase which causes lipids to collect in the spleen, liver, kidneys, and other organs. This can lead to fractures and possible death.

 

Taliglucerase is made from a human enzyme-making gene, grown in carrot cells, using a novel and transformational platform.

 

Target Health started working with Protalix in 2004 and the collaborative relationship of our 2 companies should be the standard for the pharmaceutical industry. Together, with regulatory whiz, Glen Park, PharmD at the helm at Target Health and Einat Brill Almon, PhD at the helm at Protalix, our companies took this program from preclinical to NDA in 6 years. The development program jumped from Phase 1 directly to Phase 3 and saved at least 2 years of development.

 

Our friends at Pfizer bought global rights to the drug outside of Israel.

BIO New Jersey Partnering Conference

 

Warren Pearlson, Director of Business Development, will represent Target Health at the 2012 BioNJ International BioPartnering Conference. This meeting will be held May 10-11, 2012 at the The Princeton Westin at Forrestal Village, Princeton, NJ.  Please stop by and say hello.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com

The Dark Side of Light

 

 

Melatonin is a hormone produced by the pineal gland at night. It is nicknamed “the hormone of darkness”. The pineal gland receives signals from the suprachiasmatic nucleus (SCN), the body’s master clock located in the hypothalamous of the brain

 

Light from laptops, TVs, electronics, and energy-efficient light bulbs may harm health. Humans once spent their nights in relative darkness.   No longer. When the sun sets, TVs, computers, mobile devices, and artificial lighting burn on. The May issue of the Harvard Medical School Health Letter reports that this aspect of modern life may be great for efficiency, but not for health. At night, light throws the body’s biological 1) ___ – the circadian rhythm – out of whack. Sleep suffers. The combination of poor sleep and exposure to artificial light exposure may contribute to a number of health problems. Studies have linked working the night shift and getting exposed to light at night to several types of cancer (including breast and prostate cancer), diabetes, heart disease, and obesity. It’s not exactly clear why nighttime light exposure seems to be problematic. It could be because exposure to light at night curbs the secretion of 2) ___, a hormone that influences circadian rhythms.

 

Melatonin is a hormone produced by the pineal gland of our body at night in response to darkness. The 3) ___ gland is a cone-shaped, pea-sized gland located just beneath the center of the brain. It is also called “seat of the soul” (coined by Renee Descartes), because of the influence of melatonin on emotions. Melatonin plays an important role in the following:

 

  • Regulate the circadian rhythms (daily body cycles)
  • Regulate the sleep patterns. This includes the speed of falling 4) ___, duration and the quality of sleep etc.
  • Influence hormones in the body that regulate reproduction, the timing of ovulation, and aging etc.
  • Anti-aging: Melatonin is a powerful antioxidant, a compound that blocks the action of free radicals (activated oxygen molecules) that can damage cells. Therefore some scientists suggest that it has anti-aging functions.
  • Anti-cancer: Some studies showed that melatonin may suppress the growth of certain types of cancer cells, and may stimulate the natural killer cells (a type of white blood cells) to attack tumors.

 

For people who sleep “normal hours”, natural melatonin production rises sharply in the 5) ___, and peaks between 1 am and 3 am. The peaks become smaller with advancing age after early childhood. The brain may secrete up to 20 times more melatonin at night than in the day time, hence melatonin is nicknamed “the hormone of darkness”. All light is not created equal, says the Harvard Health Letter. Blue wavelengths – which are beneficial during daylight hours because they boost attention, reaction times, and mood – seem to be the most disruptive at 6) ___. While light of any kind can suppress the secretion of melatonin, blue light does so more powerfully. In an experiment, researchers exposed people to 6.5 hours of light – either blue or green. The blue light suppressed melatonin for about twice as long as the green light and shifted circadian rhythms by twice as much. While fluorescent light bulbs and LED lights are much more energy-efficient than incandescent lights, they also tend to produce more blue light. That means the proliferation of electronic devices with screens, as well as energy-efficient lighting, is increasing exposure to blue wavelengths, especially after sundown.

 

What can you do? The editors of the Harvard Health Letter make the following recommendations:

 

  • Use dim red lights for nightlights. 7) ___ light has the least power to shift circadian rhythm and suppress melatonin.
  • Avoid looking at brightly lit screens beginning two to three hours before bed.
  • If you work a night shift or use a lot of electronic devices at night, consider wearing blue-blocking glasses.
  • Expose yourself to lots of bright light during the day, which will boost your ability to sleep at night, as well as your mood and alertness during daylight.

 

Light at night is bad for your health, and exposure to blue light emitted by 8) ___ and energy-efficient light bulbs may be especially so. Until the advent of artificial lighting, the 9) ___ was the major source of lighting, and people spent their evenings in (relative) darkness. Now, in much of the world, evenings are illuminated, and we take our easy access to all those lumens pretty much for granted. But we may be paying a price for basking in all that light. At night, light throws the body’s biological clock – the circadian rhythm – out of whack. Sleep suffers. Worse, research shows that it may contribute to the causation of cancer, diabetes, heart disease, and obesity. But not all colors of light have the same effect. Blue wavelengths – which are beneficial during daylight hours because they boost attention, reaction times, and mood – seem to be the most disruptive at night. And the proliferation of electronics with screens, as well as energy-efficient lighting, is increasing our exposure to blue wavelengths, especially after sundown.

 

Everyone has slightly different circadian rhythms, but the average length is 24 and one-quarter hours. The circadian rhythm of people who stay up late is slightly longer, while the rhythms of earlier birds fall short of 24 hours. Dr. Charles Czeisler of Harvard Medical School showed, in 1981, that daylight keeps a person’s internal clock aligned with the environment.

 

Study after study has linked working the night shift and exposure to light at night to several types of cancer (breast, prostate), diabetes, heart disease, and obesity. It’s not exactly clear why nighttime light exposure seems to be so bad for us. But we do know that exposure to light suppresses the secretion of melatonin, a hormone that influences circadian rhythms, and there’s some experimental evidence (it’s very preliminary) that lower melatonin levels might explain the association with 10) ___.

 

A Harvard study shed a little bit of light on the possible connection to diabetes and possibly obesity. The researchers put 10 people on a schedule that gradually shifted the timing of their circadian rhythms. Their blood sugar levels increased, throwing them into a prediabetic state, and levels of leptin, a hormone that leaves people feeling full after a meal, went down.

 

Even dim light can interfere with a person’s circadian rhythm and melatonin secretion. A mere eight lux – a level of brightness exceeded by most table lamps and about twice that of a night light – has an effect, notes Stephen Lockley, a Harvard sleep researcher. Light at night is part of the reason so many people don’t get enough sleep, says Lockley, and researchers have linked short sleep to increased risk for depression, as well as diabetes and cardiovascular problems. While light of any kind can suppress the secretion of melatonin, blue light does so more powerfully. Harvard researchers and their colleagues conducted an experiment comparing the effects of 6.5 hours of exposure to blue light to exposure to green light of comparable brightness. The blue light suppressed melatonin for about twice as long as the 11) ___ light and shifted circadian rhythms by twice as much (3 hours vs. 1.5 hours). In another study of blue light, researchers at the University of Toronto compared the melatonin levels of people exposed to bright indoor light who were wearing blue-light-blocking goggles to people exposed to regular dim light without wearing 12) ___. The fact that the levels of the hormone were about the same in the two groups strengthens the hypothesis that blue light is a potent suppressor of melatonin. It also suggests that shift workers and night owls could perhaps protect themselves if they wore eyewear that blocks blue light. Inexpensive sunglasses with orange-tinted lenses block blue light, but they also block other colors, so they’re not suitable for use indoors at night. Glasses that block out only blue light can cost up to $80.

 

If blue light does have adverse health effects, then environmental concerns, and the quest for energy-efficient lighting, could be at odds with personal health. Those curlicue compact fluorescent light bulbs and LED lights are much more energy-efficient than the old-fashioned incandescent light bulbs we grew up with. But they also tend to produce more 13) ___ light. The physics of fluorescent lights can’t be changed, but coatings inside the bulbs can be adjusted, so they produce a warmer, less blue light. LED lights are more efficient than fluorescent lights, but they also produce a fair amount of light in the blue spectrum. Richard Hansler, a light researcher at John Carroll University in Cleveland, notes that ordinary incandescent lights also produce some blue light, although less than most 14) ___ light bulbs.

 

ANSWERS: 1) clock; 2) melatonin; 3) pineal; 4) asleep; 5) evening; 6) night; 7) red; 8) electronics; 9) sun; 10) cancer; 11) green; 12) goggles; 13) blue; 14) fluorescent

 

 

 

Major Endocrine Organs

Niels Ryberg Finsen MD 1860-1904

 

Received the Nobel Prize in Physiology or Medicine (1903)

 

 

Niels Ryberg Finsen (December 15, 1860 – September 24, 1904) was a Faroese-Danish physician and scientist of Icelandic descent. He was awarded the Nobel Prize in Medicine and Physiology in 1903 “in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science.”

 

Niels Finsen was born in Torshavn, Faroe Islands, as the second-oldest of four children. His parents were Hannes Steingrim Finsen, who belonged to an Icelandic family with traditions reaching back to the 10th century, and Johanne Froman, who was born and raised in Iceland. When Niels was four years old his mother died, and his father remarried his mother’s cousin Birgitte Kirstine Formann, with whom he had six children. In 1871 his father was made Amtmann of the Faroe Islands. Finsen got his early education in Torshavn, but in 1874 was sent to the Danish boarding school Herlufsholm, where his older brother Olaf was also a student. Unlike Olaf, Niels had a difficult stay at Herlufsholm, culminating with a statement from the principal which claimed Niels was “a boy of good heart but low skills and energy.”

 

 

In 1882, Finsen moved to Copenhagen to study medicine at the University of Copenhagen, from which he graduated in 1890. Following graduation, he became a prosector of anatomy at the university. In 1898 Finsen was given a professorship and in 1899 he became a Knight of the Order of Dannebrog.

 

Finsen is best known for his theory of phototherapy, in which certain wavelengths of light can have beneficial medical effects. His most notable writings were “On the effects of light on the skin”, published in 1893 and “The use of concentrated chemical light rays in medicine”, published in 1896. The papers were rapidly translated and published in both German and French. In his late work he researched the effects of salt, observing the results of a low sodium diet, which he published in 1904 as “An accumulation of salt in the organism”.

 

Finsen’s Nobel Prize, held in the National Museum of Denmark.

 

 

Finsen won the Nobel Prize in Physiology in 1903 for his work on phototherapy. He was the first Scandinavian to win the prize and is the only Faroese Nobel Laureate to date.

 

Finsen’s health began to fail in the mid-1880’s. He had symptoms of heart trouble and suffered from ascites and general weakness. The sickness disabled his body but not his mind, and he continued to work from his wheelchair. He died in Copenhagen on September 24, 1904.

 

The Finsen Institute was founded in 1896, with Finsen serving as its first director. It was later merged into Copenhagen University Hospital and currently serves as a cancer research laboratory that specializes in proteolysis. A monument to Finsen designed by the sculptor Rudolph Tegner was installed in Copenhagen in 1909. It shows a standing naked man flanked by two kneeling naked women reaching up to the sky. The sculpture was entitled Towards the Light, and symbolized Finsen’s principal scientific theory that sunlight can have healing properties.

 

Award Ceremony Speech

Presentation Speech by Professor the Count K.A.H. Mörner, Rector of the Royal Caroline Institute, on December 10, 1903

 

Your Majesty, Your Royal Highnesses, Ladies and Gentlemen.

 

This year’s Nobel Prize for Physiology or Medicine has been awarded by the Council of Professors of the Caroline Institute to Professor Niels Finsen of Copenhagen in recognition of his work on the treatment of diseases, and in particular the treatment of lupus vulgaris by means of concentrated light rays. Finsen’s studies in connection with this disease constitute the most well-known and the most fruitful part of his work and are responsible for the important role played by phototherapy in medical art today. His first steps in the field of phototherapy, however, were directed towards general biological problems related to the effects of light on the organism. This led him to consider a number of specific problems concerning the effects of light on the skin in certain diseases. At first his research was not concerned with lupus but with another disease, smallpox. This first project in the field of therapeutics was certainly far removed from the principles that Finsen followed later in the treatment of lupus and other diseases, but it prepared the way none the less for his major research in this latter field.

 

In 1893 Finsen recommended the use of red light in the treatment of smallpox; this treatment, by protecting the skin against harmful light rays, was believed to facilitate the healing of the skin lesions and prevent the appearance of scars which are often the sequel to this disease. An analogous form of treatment for smallpox had in fact been in use many years before and had even been current during a part of the nineteenth century. A firm basis for this practice was lacking however. The situation was far more favorable when Finsen began his research on the subject. In 1889 Widmark’s important work had demonstrated that the most refrangible rays of the spectrum, in particular the ultraviolet rays, had a strong and specific effect on those parts of the body surface which were exposed to them. This effect is quite different from the irritations or bums produced by heat rays. At first no effect, or at the most a slight one, is apparent, but a few hours after exposure to the rays a certain degree of irritation is felt which progressively increases in intensity for about twenty-four hours and then gradually subsides. Finsen’s proposed treatment of smallpox made use of Widmark’s findings in this field. His method consisted in filtering off the ultraviolet rays by means of red glass and red curtains, etc., thus preventing their irritative effect on the affected skin, without having to keep the patient in total darkness.

 

Although this work brought recognition for Finsen, it is nevertheless of secondary importance when compared with the results of his further research. Finsen’s stroke of genius in his later work was to attempt to make therapeutic use of the powerful biological effects of highly refrangible rays. In this way he blazed the trail for scientific phototherapy and for the curative use also of other rays than those contained in ordinary light.

 

Finsen’s decision to follow this line of research was influenced by the phenomenon that light has the property of preventing the development of bacteria and even of killing micro-organisms. This phenomenon had already been observed in 1877 by Downes and Blunt and had been confirmed and studied by a number of scientists such as Duclaux, Roux, Buchner and others, on bacterial cultures, before Finsen undertook to apply it to living tissue containing bacteria. In this case also the active rays are the high-refraction rays of the spectrum. In considering the effects of light on living organisms containing bacteria, an explanation of the results obtained must take into account an essential factor other than the effect of light on pathogenic micro-organisms, namely, the already mentioned effects of light on the tissue itself. The question as to which of these two factors is most important in the therapeutic use of light will no doubt be the subject of further research. Whatever the answer may be to this question, the effective rays are the ones strongly refracted. The lower refraction rays, on the other hand, are of little use and, since they have the great disadvantage of producing combustion, must, as far as possible, be eliminated. Finsen’s method is therefore in no way comparable to certain previous attempts to treat lupus by burning the affected tissue with a burning-glass.

 

The treatment of lupus by Finsen’s method is carried out in the following way. Sunlight, or more frequently the light from a powerful electric-arc lamp (both forms containing a high proportion of active rays) is concentrated by means of lenses of appropriate composition into a beam from which the heat rays have been as far as possible eliminated; this beam is projected on a small area of affected skin, which has been drained of blood by pressure. The beam of light is applied continuously for one hour. Immediately afterwards the treated area becomes red and a little inflamed. During the next few days, this irritation of the skin increases, and then soon after begins to decrease and it is at this point that healing commences and scar tissue begins to form, which eventually produces a surface almost exactly like normal skin. Every part of the diseased area is treated consecutively, repeating the process twice on the same area if this proves necessary. This treatment has no unpleasant effects but it is expensive, requires constant supervision and considerable time. The results obtained, however, greatly outweigh these disadvantages. This method has proved of use in the treatment of a number of other skin diseases, but it has been particularly successful in the treatment of lupus vulgaris. None of the methods previously used for the treatment of this disease has produced results which can in any way be compared to those obtained with phototherapy.

 

Lupus vulgaris is, as we know, a form of tuberculosis, with localized lesions on the skin, especially that of the face, such as the nose, eyelids, lips and cheeks. The skin is gradually eroded, the face sometimes becomes dreadfully disfigured, and finally transforms patients into objects of repulsion. The chronic and progressive nature of this disease is particularly marked: it may remain active for ten years, twenty years, or even longer and, until now, it has proved resistant to all treatment. Even when patients had sufficient courage to persevere with these forms of treatment their hopes were dashed more often than not; rarely was a permanent improvement possible in this dreadful disease.

 

Thus it was that Finsen’s method was hailed as a benefit to humanity when his treatment of lupus gave results which can without exaggeration be described as brilliant.

 

Finsen began to treat his first case of lupus in November 1895. Although the method had not yet been developed far, and although the case itself was of considerable severity, having proved resistant to all the current forms of treatment most energetically applied, the results were most satisfactory. News of this success soon spread: patients suffering from lupus left their hiding places and hurried from far and near to seek a cure or some relief from their suffering. They were rarely disappointed.

 

The new method soon obtained recognition from the medical world and became current practice. It also gained considerable support from philanthropists outside medical circles. The very next year, in 1896, the Finsen Institute of Phototherapy was founded in Copenhagen with funds obtained largely from generous private donations; the State and the City authorities also contributed. This Institute, devoted to research on the biological effects of light and the practical medical application of the results obtained, has since gradually been greatly developed and improved. It is now housed in its own recently equipped building, which includes a clinical section for the treatment of patients and an experimental research laboratory. It has a large staff including 8 doctors, 53 nurses, 3 assistants, other employees and numerous domestics.

 

Finsen’s method for treating lupus is still used in the Institute. This year a report was published containing the cases of lupus treated during the first six years, up to and including November, 1901, in which 800 cases are described. The results are particularly satisfactory and are far superior to those obtained previously in the battle against this disease.

 

In 50% of these cases the skin disease was cured, although in many of them the lesions were extensive and of long standing. In a great number of cases, so much time has elapsed since the recovery that one considers this as permanent.

 

In the other 50% of these cases, in which a complete cure was not achieved, a partial cure or a  considerable improvement was obtained in most cases. In only a very small number of cases, approximately 5% of all cases, treatment was unsuccessful or produced only temporary results. From the beginning of December 1901 until the end of October of this year, 300 further cases of lupus were treated. It has been noted that in recent years the proportion of cases of early lupus is much higher than before. As Finsen has said, it seems that in Denmark the time will soon come when the last chronic cases of lupus will have disappeared. Since cases of early lupus respond more easily to treatment, the future is most encouraging.

 

This method represents an immense step forward and the work of Professor Finsen has led to developments in a field of medicine which can never be forgotten in the history of medicine. For this reason he deserves the eternal gratitude of suffering humanity.

 

An illness, from which he has long suffered, unfortunately prevents Professor Finsen from being here today.

 

I therefore ask you, Count Sponneck, as representing Denmark, to accept on behalf of Professor Finsen the tribute which the Council of Professors of the Caroline Institute pays to your eminent fellow countryman in awarding him this year’s Nobel Prize, and I am particularly happy to do so in the knowledge that this tribute has been won by a brother from over the Sund.

 

From Nobel Lectures, Physiology or Medicine 1901-1921, Elsevier Publishing Company, Amsterdam, 1967

 

DIABETES

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Two Drugs Better Than One to Treat Youth with Type 2 Diabetes Includes Avandia – It is all about benefit:risk

 

Type 2 diabetes in adults and children is closely linked to being overweight, inactive, and having a family history of diabetes. Type 2 diabetes represents 95% of diabetes cases in adults, but is much less common in children than type 1 diabetes. Type 1 diabetes, which usually strikes children and young adults, develops when the body’s immune system destroys insulin-producing beta cells in the pancreas.

 

The childhood obesity epidemic has led to the emergence of type 2 diabetes in youth. However, because type 2 diabetes has been primarily an adult illness, information about how to effectively treat youth is limited, and pediatric diabetes experts have had to rely on what is known about adult treatment. Currently, metformin is the standard treatment for young people with type 2 diabetes and the only oral drug approved for this use by the FDA. The longer a person has type 2 diabetes, the greater the likelihood of developing complications including coronary artery disease, stroke, kidney and eye disease, and nerve damage, making it critical for young people with type 2 diabetes to quickly achieve and sustain control of their blood glucose.

 

According to a study published online in the New England Journal of Medicine (29 April 2012), a combination of two diabetes drugs, metformin and rosiglitazone, was more effective in treating youth with recent-onset type 2 diabetes than metformin alone. The study also found that metformin therapy alone was not an effective treatment for many of these youth. In fact, metformin had a much higher failure rate in study participants than has been reported in studies of adults treated with metformin alone.

 

The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study is the first major comparative effectiveness trial for the treatment of type 2 diabetes in young people. TODAY was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of NIH. The TODAY study tested how well and for how long each of three treatment approaches controlled blood glucose levels in youth enrolled from ages 10 to 17 with type 2 diabetes. The study enrolled 699 youth who had type 2 diabetes for less than two years and a body mass index (BMI) at the 85th percentile or greater. BMI is a measurement of weight in relation to height. Overweight children have a BMI at the 85th to 94th percentile for their age and gender, while obesity is defined as a BMI at the 95th percentile or more. The TODAY participants had an average BMI at the 98th percentile. Participants were randomly assigned to one of three treatment groups: metformin alone, metformin and rosiglitazone together, and metformin plus intensive lifestyle changes aimed at helping participants lose weight and increase physical activity.

 

The study found that treatment with metformin alone was inadequate for maintaining acceptable, long-term, blood glucose control in 51.7% of youth over an average follow-up of 46 months. The failure rate was 38.6% in the metformin and rosiglitazone group, a 25.3% improvement over metformin alone. In the metformin plus lifestyle group the failure rate was 46.6%.

 

In September 2010, the FDA restricted the use of rosiglitazone because of studies linking the medicine to a higher risk of heart attacks and stroke in adults. The TODAY Data Safety and Monitoring Board-an independent group of health and science experts — carefully examined all safety data for TODAY participants and recommended that the study should continue to test rosiglitazone. Rosiglitazone is sold commercially as Avandia.

 

Studies have shown lifestyle-change programs to be effective in improving blood glucose control for adults with type 2 diabetes. However, the TODAY lifestyle intervention — a family-based weight-management program that included intensive education and activities delivered one-on-one by trained study staff — added no benefit to the metformin therapy. Some youth lost weight during the study, but the majority did not.

Avastin and Lucentis are Equivalent in Treating Age-Related Macular Degeneration

 

Age-Related Macular Degeneration (AMD) is the leading cause of vision loss and blindness in older Americans. In its advanced stages, the wet form of AMD spurs the growth of abnormal blood vessels, which leak fluid and blood into the macula and obscure vision. The macula is the central portion of the retina that allows us to look straight ahead and to perceive fine visual detail. Accumulation of fluid and blood damages the macula, causing loss of central vision, which can severely impede mobility and independence. Without treatment, most patients become unable to drive, read, recognize faces or perform tasks that require hand-eye coordination.

 

Both Avastin (bevacizumab) and Lucentis (ranibizumab injection) block growth of abnormal blood vessels and leakage of fluid from the vessels. Lucentis was approved by the FDA in 2006 for the treatment of AMD. Avastin is structurally similar to Lucentis, but is not approved by the FDA for AMD, but is approved for other indications in oncology. Most clinicians use these drugs on an as-needed basis when there is evidence of active disease, such as fluid leakage. However, in the original clinical trials for AMD, Lucentis was administered monthly and it was not determined if as-needed dosing would produce the same long-term visual improvements achieved with monthly administration.

 

According to the first year results of a head to head comparison of Lucentis and Avastin in the Comparison of AMD Treatments Trials (CATT), published online in the May 19, 2011 issue of the New England Journal of Medicine, Avastin and Lucentis improve vision when administered monthly or on an as needed basis. However, greater improvements in vision were seen when administration was performed monthly. Second year results were published online in the journal Ophthalmology (2 May 2012).

 

At enrollment, patients were assigned to four treatment groups defined by drug (Avastin or Lucentis) and dosing regimen (monthly or as-needed). After year one, patients initially assigned to monthly treatment were randomly reassigned to monthly or as-needed treatment without changing their drug assignment. Results showed that at two years, visual acuity with monthly treatment was slightly better than with as-needed dosing, regardless of the drug. As measured on an eye chart, monthly treatment resulted in a mean improvement of about half a line better than as-needed dosing. Switching to as-needed treatment after one year of monthly treatment yielded outcomes nearly equal to those obtained with as-needed treatment for the full two years. Changes in retinal anatomy differed by drug and frequency of treatment, but did not have an impact on vision through two years.

 

Both drugs were highly effective regardless of the approach to dosing. There was slightly less vision gain with as-needed treatment. Patients seeking the small extra advantage of monthly treatment need to be mindful of the additional burden, risks, and costs of monthly injections. Since as-needed dosing required 10 fewer eye injections over the course of two years and yielded similar visual results, many patients may choose this option.

 

Serious adverse events (SAEs) occurred at a 40% rate for patients receiving Avastin and a 32% rate for patients receiving Lucentis. Although Avastin had a higher rate of SAEs, they were distributed across many different conditions, most of which were not associated with Avastin when evaluated in cancer clinical trials, in which the drug was administered at 500 times the dose used for AMD. Fewer doses were associated with a higher rate of SAEs, which is not a typical dose-response relationship. The number of deaths, heart attacks, and strokes were low and similar for both drugs during the study. CATT was not capable of determining whether there is an association between a particular adverse event and treatment. Additional data from other clinical trials may provide information on long-term safety profiles of these drugs when used to treat AMD.

HIV

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Anti-HIV Drug Use During Pregnancy Does Not Affect Birth Size or Birth Weight

 

Tenofovir, in combination with other anti-HIV drugs, is the first line of treatment for adults with HIV. According to article published online in the journal AIDS (5 May 2012), infants born to women who used the anti-HIV drug tenofovir, as part of an anti-HIV drug regimen during pregnancy, do not weigh less at birth and are not of shorter length than infants born to women who used anti-HIV drug regimens that do not include tenofovir during pregnancy. However, at 1 year of age, children born to the tenofovir-treated mothers were slightly shorter and had slightly smaller head circumference-about 1cm each, on average-than were infants whose mothers did not take tenofovir. The study was undertaken because earlier studies had shown laboratory animals exposed to tenofovir in the womb were smaller at birth than their unexposed peers.

 

According to the authors, it was reassuring that the study did not identify any serious safety concerns during pregnancy for tenofovir.

 

Because of its safety and effectiveness, many women who have HIV take tenofovir for their health, often before they become pregnant. Similarly, because the drug is so effective for adult use and because there have been no problems reported in human infants related to their mother’s use of tenofovir, many physicians will prescribe it for pregnant women, both to safeguard the women’s health and to prevent the virus from being passed on to their infants. However, before the current study, the drug had not been specifically studied for its potential effects on infants whose mothers took it during pregnancy.

 

Over the seven years of the study, the number of participants being treated with tenofovir increased sharply. In 2003, 14% of mothers in the study had been prescribed the drug, compared with 43% in 2010.

 

The study included 2,000 U.S. infants born to HIV-positive mothers between 2003 and 2010. For 1 year, data were collected for the infants’ size relative to their gestational age (time they had spent in the womb), their birth weight, length at birth, and the circumference of their head. Results showed that mothers taking tenofovir in combination with other anti-HIV medications and mothers on anti-HIV drug combinations that did not include tenofovir gave birth to infants who were smaller, on average, than infants born to HIV-negative mothers. However, no significant differences were observed between infants from the two groups of HIV-positive mothers.

 

According to the authors, the tenofovir-exposed infant’s smaller average size and head circumference at one year of age suggests tenofovir could have a delayed effect on growth.

TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area

 

 

The following is a press release from FDA, for drug approved on May 1, 2012.  Target Health Inc. was the lead eCRO that championed this product from pre-clinical to NDA in six years.  Target Health Inc. performed all strategic planning, wrote the protocols, monitored the studies, performed data management with Target e*CRF, performed the statistical analysis and medical writing.  The NDA was paperless and prepared in eCTD format and submitted through the FDA’s Gateway.

 

 

FDA Approves New Orphan Drug to Treat a Form of Gaucher Disease

 

 

Gaucher disease occurs in people who do not produce enough of an enzyme called glucocerebrosidase. The enzyme deficiency causes fatty materials (lipids) to collect in the spleen, liver, kidneys, and other organs. The major signs of Gaucher disease include liver or spleen damage, low red blood cell counts (anemia), low blood platelet counts, and bone problems.

 

The FDA has approved Elelyso (taliglucerase alfa) for long-term enzyme replacement therapy to treat a form of Gaucher disease, a rare genetic disorder. Elelyso is an injection that replaces the missing enzyme in patients with a confirmed diagnosis of Type 1 (non-neuropathic) Gaucher disease and should be administered by a health care professional every other week. Type 1 Gaucher disease is estimated to affect about 6,000 people in the United States.

 

“Today’s approval provides for a new enzyme replacement therapy for the select number of patients with Type 1 Gaucher disease,” said Julie Beitz, M.D., director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research. “It also demonstrates FDA’s commitment to developing treatments for rare diseases.”

 

Due to the small number of affected patients, the efficacy of Elelyso was evaluated in a total of 56 patients with Type 1 Gaucher disease enrolled in two clinical trials. Many of these patients continued treatment on a longer-term extension study. In one multi-center, double-blind, parallel-dose trial, the efficacy of Elelyso for use as an initial therapy was evaluated in 31 adult patients who had not previously received enzyme replacement therapy. Patients were randomly selected to receive Elelyso at a dose of either 30 units per kilogram or 60 units/kg. At both doses, Elelyso was effective in reducing spleen volume, the study’s primary endpoint, from baseline by an average of 29% in patients receiving the 30 units/kg dose and by an average of 40% in patients receiving the 60 units/kg dose after nine months of treatment. Improvements in liver volume, blood platelet counts, and red blood cell (hemoglobin) levels also were observed.

 

In the other study, the efficacy of Elelyso was assessed in 25 patients with Type 1 Gaucher disease who were switched from imiglucerase, another enzyme replacement therapy product. In this multi-center, open-label, single-arm trial, patients who had been receiving treatment with imiglucerase for at least two years were switched to Elelyso infusions every other week at the same dose of imiglucerase. Results showed Elelyso was effective in maintaining spleen and liver volumes, blood platelet counts, and hemoglobin levels over a nine month evaluation period.

 

The most common side effects reported during clinical studies were infusion reactions and allergic reactions. Symptoms of infusion reactions include headache, chest pain or discomfort, weakness, fatigue, hives, skin redness, increased blood pressure, back pain, joint pain, and flushing. As with other intravenous protein products, anaphylaxis has been observed in some patients during Elelyso infusions. Other commonly observed side effects observed in greater than 10% of patients treated with Elelyso included upper respiratory tract infection, common cold-like symptoms (nasopharyngitis), joint pain (arthralgia), influenza, headache, extremity pain, back pain, and urinary tract infections.

 

Elelyso is manufactured and distributed by New York City-based Pfizer Inc., under license from Protalix BioTherapeutics Inc.

 

Gaucher’s Disease

Acid beta-glucosidase

 

Gaucher’s Disease is named after Philippe Gaucher MD (1854-1918)

Gaucher is remembered for his description of the disorder that was to become known as Gaucher’s disease. In 1882 while still a student, he discovered this disease in a 32-year old woman who had an enlarged spleen. At the time, Gaucher thought it to be a form of splenetic cancer, and published his findings in his doctorate thesis titled De l’epithelioma primitif de la rate, hypertrophie idiopathique de la rate sans leucemie. However, it wouldn’t be until 1965 that the true biochemical nature of Gaucher’s disease was understood.

 

Philippe Gaucher MD

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