Rare and Orphan Diseases

 

This past week, BioNJ (New Jersey) sponsored a meeting entitled: “Developing Rare Disease Regulatory Strategy Under Current Global Regulatory Statutes.“ Our friend and colleague Dr. Andrew Mulberg chaired the meeting and attendees were from patient advocacy groups, industry and FDA. There was the theme that clinical programs and regulatory strategies for rare and orphan diseases must be different from traditional development program, and that the “Totality of the Evidence“ must be part of the strategy. While there are no black and white formulas to address the “Totality of the Evidence“, it was clear that Quality of Life must be a key factor, especially when there are soft and non-validated clinical endpoints. Another striking idea was for companies collaborate with each other and FDA when working on the same indication. This way all can use the same pre-competitive natural history and available patient data, and then agree on how to study effectiveness. This would allow for the harmonization of drug development and avoid sponsors going in different directions when studying the same patient population. One exciting breakout session was on the roles of Registries both as sources of natural history data, as well a backbone for registry embedded clinical trials.

 

Target Health is very active in the orphan and rare disease spaces and we have come up with creative strategies to accelerate time to market.

 

Spring is Here, a Little Late this Year: 2018 The Big Apple

 

Last week, the 4th nor’easter storm hit New York City. It snowed all day and accumulated over 1 foot of snow in the NY metropolitan area.

 

Crocuses and others, struggle up through the snow in NYC   ©Target Health Inc.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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Small Pox, Deadlier Than Any Bomb. & Still Not Completely Destroyed

A child showing rash due to ordinary-type smallpox (variola major).

Photo credit: CDC – This media comes from the Centers for Disease Control and Prevention’s Public Health Image Library (PHIL), with identification number #4728.  Public Domain, https://commons.wikimedia.org/w/index.php?curid=4340658

 

In 2017, Bill Gates stated that bioterrorism with smallpox could be more dangerous than a nuclear weapon.

 

Smallpox is an infectious 1) ___ caused by one of two virus variants, Variola major and Variola minor. The last naturally occurring case was diagnosed in October 1977 and the World Health Organization certified the global eradication of the disease in 1980. The risk of death following contracting the disease was about 30%, with higher rates among babies. Often those who survive have extensive scarring of their skin and some are left blind. The initial symptoms of the disease include fever and vomiting. This is then followed by formation of sores in the mouth and a skin rash. Over a number of days the skin 2) ___ turns into characteristic fluid filled bumps with a dent in the center. The bumps then scab over and fall off leaving scars. The disease used to spread between people or via contaminated objects. Prevention is by the smallpox vaccine. Once the disease has developed certain antiviral medication may help.

 

There were two clinical forms of smallpox. Variola major was the severe and most common form, with a more extensive rash and higher 3) ___. Variola minor was a less common presentation, and a much less severe disease, with historical death rates of 1% or less. Subclinical (asymptomatic) infections with variola virus were noted, but were not common. In addition, a form called variola sine eruptione (smallpox without rash) was seen generally in vaccinated persons. This form was marked by a fever that occurred after the usual incubation period and could be confirmed only by antibody studies or, rarely, by virus isolation.

 

The incubation period between contraction and the first obvious symptoms of the disease is around 12 days. Once inhaled, variola major virus invades the oropharyngeal (mouth and throat) or the respiratory mucosa, migrates to regional lymph 4) ___, and begins to multiply. In the initial growth phase the virus seems to move from cell to 5)___, but around the 12th day, lysis of many infected cells occurs and the virus is found in the bloodstream in large numbers (this is called viremia), and a second wave of multiplication occurs in the spleen, bone marrow, and lymph nodes. The initial symptoms are similar to other viral diseases such as influenza and the common 6) ___: fever of at least 38.3 oC (101 oF), muscle pain, malaise, headache and prostration. As the digestive tract is commonly involved, nausea and vomiting and backache often occur. The prodrome, or pre-eruptive stage, usually lasts 2-4 days. By days 12-15 the first visible lesions – small reddish spots called enanthem – appear on mucous membranes of the mouth, tongue, palate, and throat, and temperature falls to near normal. These lesions rapidly enlarge and rupture, releasing large amounts of virus into the saliva. Smallpox virus preferentially attacks skin cells, causing the characteristic pimples (called macules) associated with the disease. A rash develops on the skin 24 to 48 hours after lesions on the mucous membranes appear. Typically, the macules first appear on the forehead, then rapidly spread to the whole 7) ___, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process takes no more than 24 to 36 hours, after which no new lesions appear. At this point variola major infection can take several very different courses, resulting in four types of smallpox disease based on the Rao classification: ordinary, modified, malignant (or flat), and hemorrhagic. Historically, smallpox has an overall fatality rate of about 30%; the malignant and hemorrhagic forms are usually fatal.

 

The last cases of smallpox in the world occurred in an outbreak of two cases (one of which was fatal) in Birmingham, United Kingdom, in 1978. A medical photographer, Janet Parker, contracted the disease at the University of Birmingham Medical School and died on 11 September 1978, after which Professor Henry Bedson, the scientist responsible for smallpox research at the university, killed himself. All known stocks of smallpox were subsequently destroyed or transferred to two WHO-designated reference laboratories with BSL-4 facilities – the United States’ Centers for Disease Control and Prevention and Russia’s State Research Center of Virology and Biotechnology VECTOR. WHO first recommended destruction of the 8) ___ in 1986 and later set the date of destruction to be 30 December 1993. This was postponed to 30 June 1999. Due to resistance from the U.S. and Russia, in 2002 the World Health Assembly agreed to permit the temporary retention of the virus stocks for specific research purposes. Destroying existing stocks would reduce the risk involved with ongoing smallpox research; the stocks are not needed to respond to a smallpox outbreak. Some scientists have argued that the stocks may be useful in developing new vaccines, antiviral drugs, and diagnostic tests; a 2010 review by a team of public health experts appointed by WHO concluded that no essential public health purpose is served by the U.S. and Russia continuing to retain virus stocks. The latter view is frequently supported in the scientific community, particularly among veterans of the WHO Smallpox Eradication Program.

 

In March 2004, smallpox scabs were found inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico. The envelope was labeled as containing 9) ___ from a vaccination and gave scientists at the Centers for Disease Control and Prevention an opportunity to study the history of smallpox vaccination in the United States. On July 1, 2014, six sealed glass vials of smallpox dated 1954, along with sample vials of other pathogens, were discovered in a cold storage room in an FDA laboratory at the National Institutes of Health location in Bethesda, Maryland. The smallpox vials were subsequently transferred to the custody of the CDC in Atlanta, where virus taken from at least two vials proved viable in culture. After studies were conducted, the CDC destroyed the virus under WHO observation on February 24, 2015.

 

In 2017, Canadian scientists recreated an extinct horse pox virus to demonstrate that the 10) ___ virus can be recreated in a small lab at a cost of about $100,000, by a team of scientists without specialist knowledge. This makes the retention controversy moot since the virus can be easily recreated even if all samples are destroyed. Although the scientists performed the research to help development of new vaccines as well as trace smallpox’s history, the possibility of the techniques being used for nefarious purposes was immediately recognized, leading to new regulation questions. Sources: nih.govcdc.gov; Wikipedia

 

ANSWERS: 1) disease; 2) rash; 3) fever; 4) nodes; 5) cell; 6) cold; 7) face; 8) virus; 9) scabs; 10) smallpox

 

Small Pox Killed Millions Throughout Human History

 

Edward Jenner (1749-1823) – Graphic credit: Vigneron Pierre Roch (1789-1872) – http://portrait.kaar.at/,http://www2.biusante.parisdescartes.fr/img/?refbiogr=8701&mod=s, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1497994

 

The scourge of the world! The history of smallpox extends into pre-history; the disease likely emerged in human populations about 10,000 BCE. An estimated 300 to 500 million people died from smallpox in the 20th century alone. This virulent disease, which kills a third of those it infects, is known to have co-existed with human beings for thousands of years. The origin of smallpox is unknown. The earliest evidence of the disease dates back to the 3rd century BCE in Egyptian mummies. The disease historically occurred in outbreaks. In 18th century Europe it is estimated 400,000 people per year died from the disease, and one-third of the cases resulted in blindness. These deaths included those of at least five reigning monarchs. As recently as 1967, 15 million cases occurred a year.

 

In 1798, Edward Jenner discovered that vaccinations could prevent smallpox. In 1967, the World Health Organization intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest in 2011. The term “smallpox“ was first used in Britain in the 15th century to distinguish the disease from syphilis, which was then known as the “great pox“. Other historical names for the disease include pox, speckled monster, and red plague.

 

The well known (Shakespeare) curse, “A pox on both your houses“ would have been a very serious utterance.

 

One of Many Stories of Smallpox (and True Love in the 19th Century)

 

Soon after his marriage, the great Irish composer and poet, Thomas Moore (1779-1852), was called away on a business trip. Upon his return he was met at the door, not by beauteous Elizabeth, bride and the love of his life, but by the family doctor. “Your wife is upstairs,“ said their doctor. “But she asked that you not come up.“ The physician related the terrible account; Moore learned that; his wife had contracted small pox. The disease had left her once flawless skin pocked and scarred. She had taken one look at her reflection in the mirror and commanded that the shutters be drawn and over them the heavy drapes, and that her husband should never see her again. Moore would not listen. He ran upstairs and threw open the door of his wife’s room. It was black as night inside. Not a sound came from the darkness. Groping along the wall, Moore felt for the gas jets. A startled cry came from a black corner of the room. “No! Don’t light the lamps!“ Moore hesitated, swayed by the pleading in the voice. “Go!“ she begged. “Please go! This is the greatest gift I can give you now.“

 

Moore did go. He went down to his study, where he sat up most of the night, passionately writing, what turned out to be one of the greatest love poems ever written; but he also composed a song, to go with his words, a song that lives on, using certain musical phrases of ancient Irish melodies. He had never written a song before, but now it came naturally, motivated by the adoration of his wife and her profound melancholy. The next morning, as soon as the sun was up he returned to his wife’s room. In spite of the morning light, her room remained as dark as night. He felt his way to a chair and sat down. “Are you awake?“ he asked. “I am,“ came a voice from the far side of the room. “But you must not ask to see me. You must not press me, Thomas.“ “I will sing to you, then,“ he answered. And so, for the first time, Thomas Moore sang to his wife the song that still lives today:

 

Believe me, if all those endearing young charms,

Which I gaze on so fondly today,

Were to change by tomorrow and flee in my arms,

Like fairy gifts fading away,

Thou wouldst still be adored, as this moment thou art —

Let thy loveliness fade as it will,

 

Moore heard a movement from the dark corner where his wife lay in her loneliness, waiting.  He continued:

 

Let thy loveliness fade as it will,

And around the dear ruin each wish of my heart

Would entwine itself verdantly still —

 

The song ended. As his voice trailed off on the last note, Moore heard his bride rise. She crossed the room to the window, reached up and slowly pulled aside the drapes and drew open the shutters.

 

Their long marriage was successful with five children, who tragically all died before both parents. Towards the end of his life, Moore suffered from a stroke and was lovingly cared for by his devoted wife, Elizabeth. He died on 26 February 1852. His remains are in a vault at St. Nicholas churchyard, Bromham, within view of his cottage-home.

 

(Editor’s note: as you listen to this loveliness, try not to look at the photos; would not have been our choice)

 

Here is that same love poem/song:

 

Believe Me If All Those Endearing Young Charms

 

Another version of: “Believe Me

 

Another version of: “Believe Me

 

Final evolution of the music; Harvard University’s song, “Fair Harvard.“

 

The Last Rose of Summer, words and music by Thomas Moore, sung by Renee Fleming. The haunting melody of Moore’s, The Last Rose of Summer, was adapted by Beethoven, Mendelssohn and Flotow in his opera, Martha.

 

Dame Joan Sutherland: Last Rose (adapted for the opera, Martha)

 

Mendelssohn, (adaption) Fantasie Opus #15

 

Beethoven: (adaptation) e flat; “Sad and luckless was the season.“

 

FINAL NOTATION: THE LAST ROSE OF SUMMER, IS A PROMINENT MELODY IN THE SOUND TRACK OF “THREE BILLBOARDS OUTSIDE EBBING, MISSOURI,” A RECENT FILM NOMINATED FOR AN OSCAR.

 

Atypical Brain Development Observed in Preschoolers with ADHD Symptoms

 

Attention deficit hyperactivity disorder (ADHD) is a mental disorder of the neurodevelopmental type, characterized by a pattern of inattention, hyperactivity and impulsive behavior not age appropriate. The symptoms appear 1) before a person is 12 years old, 2) are present for more than six months, and 3) cause problems in at least two settings (such as school, home, or recreational activities).

 

According to an article published in Journal of the International Neuropsychological Society (26 March 2018), children as young as 4 years old with symptoms of ADHD may have significant differences in brain structure, compared to children without such symptoms. The study is the first comprehensive examination of brain structure changes in preschoolers with signs of ADHD. Previous studies have documented brain differences in adolescents with ADHD. However, few studies have looked for such differences in preschoolers, despite research citing ADHD as the most commonly diagnosed psychological disorder among young children.

 

The study included 90 young children: 38 typically developing preschoolers and 52 preschoolers with symptoms of ADHD. Results showed that the children’s scans revealed that those with ADHD symptoms had multiple areas with less brain matter volume than their typical peers, and these differences were consistent with parent reports of hyperactive and impulsive behaviors. The authors cited challenges collecting data, mainly getting youngsters to lie still during the brain scan, particularly children with ADHD-associated behavior. It is possible that the children who were eventually scanned had more moderate symptoms and, therefore, were better suited to participate in the study. The authors speculated that children with more severe ADHD may have more pronounced brain differences. The authors will continue to follow the children, monitoring brain changes or differences as the they grow older. The study provides the groundwork for future analysis of structural and functional brain changes in ADHD, which the authors hope will provide new insights into how symptoms of the disorder relate to differences in the brain.

 

Islet Transplantation Improves Quality of Life for People With Hard-to-Control Type 1 Diabetes

 

Diabetes mellitus type 1 (also known as type 1 diabetes) is a form of diabetes mellitus in which not enough insulin is produced, resulting in high blood sugar levels in the body. Pancreatic islets release the hormone insulin, which helps control blood glucose levels. In type 1 diabetes, the body’s immune system attacks and destroys the insulin-producing cells in islets. People with the disease must take insulin to live, but insulin injections or pumps cannot control blood glucose levels as precisely as insulin released naturally from the pancreas. Even with diligent monitoring, blood glucose can often reach levels that are higher or lower than normal. A low blood glucose level, or hypoglycemia, typically is accompanied by tremors, sweating, nausea and/or heart palpitations. These symptoms prompt the person to eat or drink to raise their blood glucose. However, some people do not experience these early warning signs. This impaired awareness of hypoglycemia raises the risk of potentially life-threatening severe hypoglycemic events, during which the person is unable to treat himself or herself. These episodes can lead to accidents, injuries, coma and death.

 

According to an article published online in Diabetes Care (21 March 2018), quality of life for people with type 1 diabetes who had frequent severe hypoglycemia — a potentially fatal low blood glucose (blood sugar) level — improved consistently and dramatically following transplantation of insulin-producing pancreatic islets. The results come from a Phase 3 clinical trial funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), both part of the National Institutes of Health. The trial enrolled 48 people with type 1 diabetes who had hypoglycemia unawareness — an impaired ability to sense drops in blood glucose levels — and experienced frequent episodes of severe hypoglycemia despite receiving expert care. Results showed the greatest improvements in diabetes-related quality of life. Islet recipients also reported better overall health status after transplant, despite the need for lifelong treatment with immune-suppressing drugs to prevent transplant rejection. The authors observed these improvements even among transplant recipients who still required insulin therapy to manage their diabetes.

 

Previously reported clinical outcomes from the trial  showed that islet transplantation prevents severe hypoglycemia and improves blood glucose awareness and control. The study was conducted by the NIH-funded Clinical Islet Transplantation Consortium.

 

For the study, all 48 study participants received at least one islet transplant. One year after their first transplant, 42 participants (88 percent) were free of severe hypoglycemic events, had established near-normal blood glucose control, and had restored awareness of hypoglycemia. Only a small number of functional insulin-producing cells are necessary to restore hypoglycemic awareness, but this amount may not be sufficient to fully regulate a person’s blood glucose levels. Approximately half of the transplant recipients needed to continue taking insulin to control their blood glucose levels. The study design incorporated four well-established, commercially available quality-of-life surveys that were given to participants repeatedly before and after islet transplantation. Two of the surveys were specific for diabetes, while two assessed health more generally. Reported improvements in quality of life were similar among islet recipients who still needed to take insulin to manage their diabetes and those who did not. The authors concluded that elimination of severe hypoglycemia and the associated fears accounted for these improvements, appearing to outweigh concerns about the need to continue insulin injections.

 

Islet transplantation is an investigational therapy in the United States. While promising for people whose type 1 diabetes cannot be controlled with standard treatments, the procedure is not appropriate for most people with type 1 diabetes, as there are risks associated with the transplant procedure, such as bleeding, as well as side effects of immunosuppressive medications, such as decreased kidney function and increased susceptibility to infections.

 

FDA Expands Approval of Blincyto for Treatment of B-Cell Precursor ALL in Patients Who Have a Certain Risk Factor for Relapse

 

B-cell precursor ALL is a rapidly progressing type of cancer in which the bone marrow makes too many B-cell lymphocytes, an immature type of white blood cell. The National Cancer Institute estimates that approximately 5,960 people in the United States will be diagnosed with ALL this year and approximately 1,470 will die from the disease.

 

The FDA has granted accelerated approval to Blincyto (blinatumomab) to treat adults and children with B-cell precursor acute lymphoblastic leukemia (ALL) who are in remission but still have minimal residual disease (MRD). MRD refers to the presence of cancer cells below a level that can be seen under the microscope. In patients who have achieved remission after initial treatment for this type of ALL, the presence of MRD means they have an increased risk of relapse. According to FDA, this is the first FDA-approved treatment for patients with MRD-positive ALL, and because patients who have MRD are more likely to relapse, having a treatment option that eliminates even very low amounts of residual leukemia cells may help keep the cancer in remission longer.

 

Blincyto works by attaching to CD19 protein on the leukemia cells and CD3 protein found on certain immune system cells. Bringing the immune cell close to the leukemia cell allows the immune cells to attack the leukemia cells better. The FDA first approved Blincyto under accelerated approval in December 2014 for the treatment of Philadelphia chromosome (Ph)-negative relapsed or refractory positive B-cell precursor ALL. Full approval for this indication was granted in July 2017, and at that time, the indication was also expanded to include patients with Philadelphia chromosome-positive ALL.

 

The efficacy of Blincyto in MRD-positive ALL was shown in a single-arm clinical trial that included 86 patients in first or second complete remission who had detectable MRD in at least 1 out of 1,000 cells in their bone marrow. Efficacy was based on achievement of undetectable MRD in an assay that could detect at least one cancer cell in 10,000 cells after one cycle of Blincyto treatment, in addition to the length of time that the patients remained alive and in remission (hematological relapse-free survival). Overall, undetectable MRD was achieved by 70 patients. Over half of the patients remained alive and in remission for at least 22.3 months.

 

The side effects of Blincyto when used to treat MRD-positive B-cell precursor ALL are consistent with those seen in other uses of the drug. Common side effects include infections (bacterial and pathogen unspecified), fever (pyrexia), headache, infusion related reactions, low levels of certain blood cells (neutropenia, anemia), febrile neutropenia (neutropenia and fever) and low levels of platelets in the blood (thrombocytopenia). Blincyto carries a boxed warning alerting patients and health care professionals that some clinical trial participants had problems with low blood pressure and difficulty breathing (cytokine release syndrome) at the start of the first treatment, experienced a short period of difficulty with thinking (encephalopathy) or other side effects in the nervous system. Serious risks of Blincyto include infections, effects on the ability to drive and use machines, inflammation in the pancreas (pancreatitis), and preparation and administration errors – instructions for preparation and administration should closely be followed. There is a risk of serious adverse reactions in pediatric patients due to benzyl alcohol preservative; therefore, the drug prepared with preservative free saline should be used for patients weighing less than 22 kilograms.

 

This new indication for Blincyto was approved under the accelerated approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study in randomized controlled trials is required to verify that achieving undetectable MRD with Blincyto improves survival or disease-free survival in patients with ALL.

 

The FDA granted this application Priority Review and it received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

 

Fifteenth Century Sephardic Sweetness

Although this week’s recipe has been adapted from a 15th Century Sephardic one, if’s so overwhelmingly flavorful, it has evolved to take its place on any holiday table, or any table, any day, for that matter. We really hope you will give it a try. This concoction will not disappoint. ©Joyce Hays, Target Health Inc.

 

Ingredients

2 cups Spanish Marcona blanched almonds, plus about 30 extra Marcona almonds for decoration

1 cup granulated sugar

1 large egg

Finely grated zest of 1 lemon

White chocolate blocks

Blue sprinkles (decoration)

Blue dark chocolate bits (decoration), or

Blue coated almonds (for decoration) or

Blue marzipan, for decoration

 

Basically a 5-ingredient recipe, not counting the decorations. It couldn’t be any easier. Isn’t chemistry wonderful! It’s unbelievable that these little taste treats are so delicious with so little effort! Of course, in the 15th Century there were none of the kitchen conveniences we have now. ©Joyce Hays, Target Health Inc.

 

Directions

1.     Zest the lemon

 

Zest the lemon. ©Joyce Hays, Target Health Inc.

 

2. Measure out the sugar and the almonds.

3. Using a food processor equipped with a metal blade, grind 2 cups almonds extremely well; until they begin to resemble almond flour.

4. Add 3/4 cup sugar, the egg and lemon zest, and pulse until the mixture begins to resemble dough, that you will be able to roll in your hands later.

5. Put the dough in a medium bowl, cover and refrigerate for at least 12 hours.

 

The almonds have been ground down to a rough flour ( they will continue to be ground down) and now the sugar is added to the food processor, for more grinding. ©Joyce Hays, Target Health Inc.

 

Now adding the egg and the lemon zest, for more grinding. ©Joyce Hays, Target Health Inc.

 

This dough will be covered with saran wrap and refrigerated overnight. ©Joyce Hays, Target Health Inc.

 

6. Preheat oven to 350 degrees.

7. Line a baking sheet with parchment paper.

8. Grate or shred the white chocolate into a small bowl.

 

Most good markets, like Whole Foods or Fairway, sell blocks of white and dark chocolate. ©Joyce Hays, Target Health Inc.

 

Do-it-yourself, shredded white chocolate. ©Joyce Hays, Target Health Inc. 

 

9. Place remaining 1/4 cup sugar in a small bowl.

10. Pinching off pieces of dough about the size of a walnut, roll them first into balls, then into sugar. Only roll in sugar, the cakes that will not be dipped in white chocolate. Also, plan ahead. Don’t put an almond into the center of cakes that will later, be dipped into chocolate.

11. For plain cakes without chocolate, slowly press a whole almond, half-way into the center of each cake. On a baking sheet, place cakes one inch apart.

 

Roll the dough into small balls, the size of a walnut. ©Joyce Hays, Target Health Inc.

 

12. Bake until cookies have barest hint of color but still remain soft, 8 to 10 minutes. (Cookies must be soft when removed from oven to avoid excess hardening when they cool.)

13. Cool completely, and store in an airtight container.

 

Going into the oven. ©Joyce Hays, Target Health Inc.

 

Out of the oven, here’s a different batch, some baked with a whole almond and some without. The ones without an almond, will be dipped, after cooling completely, into melted white chocolate. ©Joyce Hays, Target Health Inc.

 

For variation, consider dipping all or some of these little cakes into white (or dark) chocolate, melted in a small frying pan over very low heat. For dipping, try using a combination of tongs to dip with, then transfer from tongs to a tablespoon or larger spoon. Push from the spoon, onto a plate or on parchment, to let them harden. While the chocolate is still soft, dust with a scant sprinkling of blue sugar then the tiny blue covered chocolate decoration or blue candied almond, or blue marzipan ball.

 

Over low heat, melt the white chocolate, for dipping. © Joyce Hays, Target Health Inc.

 

Parchment is so convenient to keep in the kitchen all the time. In this recipe it was used for baking, cooling and finally for cakes that were dipped, then put back on the same baking parchment, to harden and to decorate. Then you just throw it away, after putting the cakes on a serving platter. ©Joyce Hays, Target Health Inc.

 

I bought the blue sugar granules from Nuts.com. ©Joyce Hays, Target Health Inc.

 

They taste as good as they look.  ©Joyce Hays, Target Health Inc.

 

A beautiful holiday presentation.  ©Joyce Hays, Target Health Inc.

 

One of the first experiments, gone the next day.  ©Joyce Hays, Target Health Inc.

 

Beautiful holidays celebrated at the same time. We hope everyone is having a joyous and flavorful weekend. ©Joyce Hays, Target Health Inc.

 

Have a great week everyone!

From Our Table to Yours

Bon Appetit!