Edgar toddler first ‘bubble boy’ survivor

State-mandated test at birth identified fatal disease

By Megan Loiselle
Wausau Daily Herald

EDGAR — A 1-year-old Edgar boy has become the first child in the world to be saved from a fatal immunodeficiency disease, just months after Wisconsin became the only state to test for it at birth.

Dawson Bornheimer’s family on Sept. 25 celebrated the first anniversary of a lifesaving bone marrow transplant that treated his Severe Combined Immunodeficiency, or SCID — also known as “bubble boy disease.” The disease is fatal if not treated in the first few months of life.

The state’s pilot program for the screening was funded in part by the Jeffrey Modell Foundation, established by Vicki and Fred Modell in memory of their son who died at age 15. Dawson was honored as the “man of the year” by the foundation at a gala this spring in New York. The screening now is routine for the estimated 70,000 births in the state annually.

“They caught it, and because of that, we get to play with you every day,” his mother, Melissa Bornheimer, said during an interview at her home, as she patted Dawson’s leg.

Twelve days after Dawson was born on June 12, 2008, the Bornheimers received a call saying he had failed the test for SCID — a test they didn’t even know he had been given.

Melissa said at first she thought the test had to be wrong because Dawson seemed fine.

Hours after the call, the Bornheimers took Dawson to the hospital with a fever. He was released with what doctors said was a viral infection. Days later, his belly button became infected so badly that it had to be removed at a hospital in Madison.

In a span of a few weeks in August, Dawson was checked into the Children’s Hospital of Wisconsin in Milwaukee for a blood transfusion as well as surgeries to remove abscesses growing on his neck and to fix a hole in his trachea. Test results showed his bone marrow wasn’t producing white blood cells strong enough to attack infections in his body. The only cure would be a bone marrow transplant.

On Sept. 25, 2008, he received the transplant, with marrow donated from a baby in Germany. Some of Dawson’s vital organs shut down as his body struggled to adjust to the donor’s marrow, but Melissa said his body eventually accepted the bone marrow.

One year after the transplant, Dawson still has 100 percent of his donor’s bone marrow, which means chemotherapy he received last year was successful in eradicating all of his own bone marrow.

Melissa, 35, said the couple had great health insurance through Mike’s work as a material handler at Wausau Supply Co. It allowed the family to focus on Dawson rather than worrying about his $1 million in treatment costs.

Today, Dawson often crawls around the floor and plays at home with his 9-year-old brother, Dylan. Dawson will start walking soon.

His grandmother Ione Bornheimer of Athens said every time she and her husband, Harvey, visit, they see more improvements.

“He’s making big strides,” she said. “It has been very hard on the family but he’s our little miracle baby.”
linkback url: http://www.wausaudailyherald.com/article/20091008/WDH0101/910080625/1981/WDHopinion

‘Olivia’s Fund’ gets barbecue boost

The Silliker family and supporters are grateful to the community for its support. As a result of that support, Olivia Silliker’s (small photo) future is considerably brighter following a bone marrow transplant courtesy of her four-year-old sister Mackenzie.

Community support

Family and friends of Olivia Silliker are overwhelmed by the community spirit and generosity displayed at a fund-raising barbecue outside Chrissy’s Variety Store.

The recent barbecue raised $1,500, for which the family and supporters wished to express thanks from the bottom of their hearts.

Olivia was born June 9th to parents Mark and Anna and hospitalized August 5th with a diagnosis of ADA SCIDS (Severe Combined Immunodeficiency). In layman’s terms, the rare (one in every two million births) condition means her immune system does not function properly, and a common cold can be deadly

Treatment for ADA SCIDS is a bone marrow transplant.

The immediate family was tested and a perfect match found in Olivia’s four-year-old sister Mackenzie. One week after admission to Sick Kids hospital in Toronto, the transplant took place with the support of a very brave older sister. Mackenzie has since recovered from the procedure and attended her first day of school September 22nd.

Olivia remains in Sick Kids, in an isolation room, which filters air 500 times per hour. To interact with Olivia, her family needs to protect her from germs by using sterile gowns, gloves, hairnet, boots and masks.

It is unknown how long she must be in the hospital, but her family has been told to prepare for a lengthy stay. Olivia’s blood is taken regularly to ensure her white blood cells are increasing and tests are done to determine whether the bone marrow transplant was a success. She will not be released until it is positive that she has developed an immune system and will be able to fight infection on her own.

In the interim, Anna’s desire to remain with her daughter is being challenged by financial realities. Her maternity leave from a subsequently-closed plant (DDM) will come to an end, highlighting the additional financial pressures of living costs and travel expenses exacerbating the family’s natural stress caused by their daughter’s medical challenges.

Fund-raising efforts have been organized, including the barbecue, in order to provide financial assistance for Anna to stay by Olivia’s side through accommodation at Ronald McDonald House in Toronto, as well as with monthly bills and everyday living expenses.

“I would rather sell my house than leave her there all alone,” said Anna.

Additional fundraisers will occur over the next few months, however friends and family are encouraging the public to donate whenever possible to assist the Silliker family.

Donations can be made at St. Mary’s Roman Catholic Church in Tillsonburg. Cheques are to be made payable to St. Mary’s RC Church specifying that the donation is for “Olivia’s Fund” and a tax receipt will be issued.

linkback url: http://www.tillsonburgnews.com/ArticleDisplay.aspx?e=2047035

Scientists Identify Genetic Cause of Previously Undefined Primary Immune Deficiency Disease

Researchers at the National Institutes of Health have identified a genetic mutation that accounts for a perplexing condition found in people with an inherited immunodeficiency. The disorder, called combined immunodeficiency, is characterized by a constellation of severe health problems, including persistent bacterial and viral skin infections, severe eczema, acute allergies and asthma, and cancer.

The team that made the discovery was led by Helen Su, M.D., Ph.D., at the National Institute of Allergy and Infectious Diseases (NIAID), and included collaborators from NIAID and the National Cancer Institute (NCI). The research is reported in this week’s New England Journal of Medicine.

“NIH clinicians have cared for people with unusual and difficult-to-treat immune disorders for decades,” says NIAID Director Anthony S. Fauci, M.D. “This study exemplifies their commitment to improving the lives of people with these diseases by trying to uncover the causes of these disorders and thereby better understanding how to treat them.”

Combined immunodeficiency is a type of primary immune deficiency disease (PIDD) in which several parts of the immune system are affected. This inherited disorder is characterized by increased susceptibility to bacterial, viral and fungal infections of various organs of the body. In some cases, susceptibility to cancers also may be seen.

There are 150 known PIDDs. Approximately 500,000 people in the United States have been diagnosed with a PIDD, while many more remain undiagnosed.

The NIAID and NCI investigators recognized that certain patients with an undefined form of combined immunodeficiency shared enough clinical features to make it likely that the cause might be a common genetic mutation. Originally, these individuals were thought to have a variant form of hyper-immunoglobulinema E syndrome (HIES), a disorder characterized by increased levels of a class of antibodies known as immunoglobulin E, superficial and systemic bacterial and fungal infections, and atopic dermatitis, also known as eczema.

This newly described group, however, had far more severe eczema than is typical in people with variant HIES.  They also had extensive and difficult-to-manage viral infections of the skin, such as warts, molluscum contagiosum—a type of poxvirus that only infects the skin—and herpes simplex. Some in this group also developed skin cancers, as well as lymphoma of the skin.

“Even though these individuals were diagnosed with a more uncommon form of HIES, they were still considered to have a mystery disease, because they had severe allergies and had developed cancers,” says Dr. Su.

Using a technique called comparative genomic hybridization, a process by which large amounts of DNA is fixed to a computer chip and analyzed for changes in the genes, scientists examined the genes in the tissue samples from five different groups:  the 11 individuals with the unknown immunodeficiencies, people with the variant form of HIES, people with classic HIES, those with other immunological diseases, and healthy individuals.

The researchers discovered that people with the unique form of HIES had mutations in a gene called DOCK8 that led to deletions in parts of the gene. The normal function of DOCK8 is currently unknown.

When compared with healthy individuals, the people with DOCK 8 mutations had fewer CD8 positive T cells, immune cells needed to fight viral infections; fewer antibody-producing B cells; and increased numbers of eosinophils—immune cells associated with allergy.

According to Dr. Su, these findings indicate that DOCK8 is essential for defense against viral infections and for preventing the development of cancer and allergies.

Although further study is required to determine if DOCK8 mutations occur in other people with similar disease symptoms, DOCK8 immunodeficiency syndrome may be a new PIDD. These findings mean that individuals with this rare disease will be able to receive a more accurate diagnosis. Identifying a genetic cause for the disease provided comfort to some of those diagnosed who had battled an unknown immune disease for years, according to Dr. Su.

“The study of inherited disorders and the genetic alterations that are responsible for their complex array of disease symptoms has often resulted in the discovery of causative genes that play a role in cancer initiation,” said NCI Director John E. Niederhuber, M.D. “The disease mutations found in this study in the DOCK8 gene exemplify that kind of important finding.  As with any discovery of a genetic defect, the challenge going forward is to develop a complete knowledge of the cascading pathways of biological function for which DOCK8 is responsible.”

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The National Institutes of Health (NIH)—The Nation’s Medical Research Agency—includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

###

Reference:

Zhang et al. DOCK8 mutations underlie a new form of combined immunodeficiency with allergy, hyper-immunoglobulinemia E, lymphocyte dysfunction, viral infections, and cancer. New England Journal of Medicine DOI: 10.1056/NEJMoa0905506 (2009).

linkback url: http://www3.niaid.nih.gov/news/newsreleases/2009/DOCK8.htm

The Second Coming of Gene Therapy
09.02.2009
For years, gene therapy produced tons of hype but no results. Recently, though, new approaches have yielded its first successes: breakthrough treatments for blindness, cancer, and the deadly bubble boy disease.
by Jill Neimark

“For the first two years of her life, my daughter, Katlyn, was knocking on heaven’s door every day,” says Daisy Demerchant, a 26-year-old mom living in Centreville, New Brunswick, just north of Maine. “Two months after she was born she started getting sick, and she never got better.” At six months Katlyn was diagnosed with “bubble boy” disease, formally known as severe combined immunodeficiency (SCID), which robs the immune system of the ability to fight infection. There are many causes of this disorder; in Katlyn’s case it was lack of the enzyme adeno­sine deaminase, or ADA, which rids the body of a natural toxin called deoxyadenosine. When the toxin builds up, it destroys T and B lymphocytes, the body’s infection-fighting immune cells. As a result, Katlyn’s immune cells were dying.

Treatment options ranged from risky to grim. One was a bone marrow transplant, in which imported donor cells could manufacture healthy T cells to fight invading germs. But bone marrow transplants can have lethal complications and often require drugs that further inhibit the patient’s immune system, leaving a window of vulnerability until the transplant kicks in. Another potential treatment involved injections of the ADA enzyme itself. But there was a risk Katlyn would develop antibodies to the drug, rendering it useless. Without any treatment at all, she would simply die.

While weighing their options, doctors put the little girl on protective antimicrobials and sent her to a hospital eight hours from her home. She became another fragile bubble baby sequestered from the world. “My husband quit his job building fire trucks, and we lived with Katlyn in the hospital for 15 months,” Demerchant says. The parents had to wear sterile gowns, booties, masks, and gloves, and the urge to touch their child—let alone hug and kiss her—had to be put on hold.

Just when it seemed as if Katlyn’s life might never improve, science and fate intervened. Her specific condition, called ADA-SCID, had long tantalized researchers seeking to repair genetic defects with a technique called gene therapy. Rare, deadly, and caused by a single gene mutation, it was a perfect proof-of-principle condition for anyone seeking to replace damaged DNA with genes that did the job. With all her troubles, little Katlyn Demerchant had been almost made to order for Fabio Candotti, a senior investigator at the National Human Genome Research Institute at the National Institutes of Health in Bethesda, Maryland.

Before Katlyn showed up at NIH, the doctors there were already well prepared: They had inserted healthy human ADA genes into a modified mouse retrovirus—a type of virus that can enter human cells and transfer new genetic material right into the DNA strands in their nuclei.

Once Katlyn arrived in May 2007, Candotti and his team removed stem cells from her bone marrow and exposed them to the engineered retrovirus, creating a human-virus hybrid. Then they injected the hybrid cells back into Katlyn. Like heat-seeking missiles, the retooled stem cells automatically found their way back home to the marrow. There, they began to specialize, creating all of the secondary or “daughter” cells that such stem cells normally produce—including healthy T cells with functioning ADA genes.

Everybody waited while Katlyn, still stuck inside the bubble, learned to walk on the floor of her sterile isolation room and to play through the protective window with a visiting dog named Toffee. On September 3, blood tests showed Katlyn’s immune system was being populated with robust, functioning T cells. She was so restored, in fact, that her parents were able to take her outside for the first time since she was an infant. “The first day we took her out she was really quiet and a little terrified,” Daisy Demerchant says. “The second time she started running around and asking us a million questions. She’d point to the sun, clouds, leaves, cars, everything imaginable, and ask us what it was. Ever since that day, she has never wanted to stay inside.”

Six months after her gene therapy transplant, Katlyn was so healthy that doctors let her return home to Canada. It can take a year or longer for the immune system to reconstitute itself in full, so Katlyn still takes antimicrobials as a precaution, but today she plays outside, even in the dirt, and is resistant enough to fly on a commercial plane.

The new DNA treatments for Katlyn Demerchant and other bubble babies are nothing short of remarkable, the culmination of a major push to perfect gene therapy for the disease, Candotti says. Across the ocean, in Italy, bubble babies with ADA-SCID are also being cured: A trial led by Alessandro Aiuti, a molecular biologist at San Raffaele Telethon Institute for Gene Therapy in Milan, restored the immune system in eight of ten children, while a ninth had significant improvement.

And bubble babies are far from alone. In Europe and the United States, gene therapists have restored vision in individuals suffering from a rare genetic disorder that inevitably leads to blindness. In Texas, a team has manipulated genes in order to put deadly cancers into complete remission. Building on these successes, gene therapy may soon be used to correct hereditary genetic diseases like cystic fibrosis, hemophilia, and Tay-Sachs and to activate the immune response against a wide variety of infectious diseases and cancers. Gene therapy and its adjuncts may help us trick the body into growing new tissue to rejuvenate arthritic joints, fix injured hearts, and speed the healing of wounds….Continued

link url: http://discovermagazine.com/2009/sep/02-second-coming-of-gene-therapy

Campers aid area toddler

The Jeffery family is giving thanks to their newfound friends, many of whom they’ve never met.

Indeed, most of the Jefferys’ supporters are members of the Bluewater Campers’ Association, which recently presented the St. Joseph’s family with a $7,200 donation, the second of such gifts since the club first heard of the family’s plight three years ago.

“I can’t tell you what this means for our family,” says Dennis Jeffery. “This will help a lot.”

And help is what the Jefferys need as their youngest son, three-year-old André, continues with his valiant battle with Severe Combined Immunodefiency Disease (SCID), an autoimmune disease that leaves him vulnerable to a host of life-threatening illnesses and renders most of his life to the confines of what is commonly known as a plastic bubble.

André was first diagnosed with the disease at the age of four months when the Jefferys brought him to see a Stratford doctor as the baby was covered in a rash that looked like he’d been splashed with scalding water.

André has been in and out of hospitals ever since.

Most recently, the sweet-cheeked young lad with soulful brown eyes, suffered cardiac arrest, his second one due to the havoc the 34 medications medications he takes daily are wreaking on his organs.

André is now at Sick Kids’ Hospital in Toronto where his mom, Sheila, keeps vigil as the rest of the family including seven-year-old sister, Monica, and nine-year-old brother, Donavon, hold down the fort in St. Joseph’s.

Naturally, notes Dennis, the emotional, financial and physical toll of André’s plight is difficult on everyone, especially André’s siblings who must spend a lot of time away from their beloved parents who, for a time, were at André’s bedside 24 hours a day.

“It’s hard to keep everybody together,” notes Dennis. “It’s been a difficult experience. I wouldn’t wish it on my worst enemy.

And when André and his mom are able to return home, the family will once again face the additional expenses of bringing Registered Nurses in to assist with his care. Plus, only 27 of the medications André requires are covered by OHIP.

At a recent meeting at the Bluewater Campers’ meeting room, club members presented the family with the $7,200 donation, as well as $50 gift certificates for Monica and

Donavon and a stuffed animal for André. It was clearly a proud night for members as one organizer put it: “For such a small number of people, this is an amazing amount of money.”

While learning André is currently grappling with kidney problems as he recovers from cardiac arrest, the Bluewater Campers vow to continue to help where they can – even though most of them were meeting Dennis, Monica and Donavon for the first time at the cheque presentation.

“It’s going to help me large,” says Dennis, who notes there are many changes on the horizon for the Jefferys including the possibility that they will have to sell their St. Joseph’s home, a community where both Dennis and Sheila hail from, and move to Toronto to ensure Andre continues to receive the treatment he needs.

Club member Deb Jeffrey, in thanking the campers, note the relatively small park – at 140 trailers – has raised nearly $20,000 in the past three years for the Jefferys and other community-based causes including $3,000 for Habitat for Humanity and $2,500 for the CT Scanner campaign at Alexandra Marine General Hospital in Goderich last year, and about $3,000 for the Jefferys two years ago.

The fundraising events, note organizers, were made possible through a slew of events, including silent auctions and golf tournaments with prizes donated by a vast number of area businesses and community groups. A special cake made each year proves to be a hot ticket item as well as it raised $350 during the first year, $550 the second and $1,400 this year.

linkback url: http://www.clintonnewsrecord.com/ArticleDisplay.aspx?e=1716515

(UKPA) – Sep 1, 2009

When it was suggested that her very sick daughter have a new bone marrow transplant procedure at Great Ormond Street Hospital (GOSH), Louise Moseley said she was just relieved that Ffion was not the first.

“I would have been more sceptical if she had been the first but other parents had been brave enough to say yes. She was so poorly we just thought that it had to be done.”

Ffion was just three weeks old when she developed skin problems that were so serious that she was regularly in hospital.

It was initially thought to be dermatitis but when Ffion was transferred to the Singleton Hospital in Swansea it was suggested the condition was likely to be caused by a problem with her immune system.

Ffion was three months old when she was diagnosed with the genetic condition Omenn Syndrome, a severe combined immunodeficiency (Scid), and admitted to GOSH.

“All I heard was ’she needs a bone marrow transplant. It’s a fatal condition’,” said Mrs Moseley, 30, of Pembroke Dock, Dyfed. “It was a complete shock. I’d never heard of it because it’s such a rare condition.”

Too sick to have the chemotherapy needed for a conventional transplant, Ffion was given the new procedure using antibodies to prepare her for the transplant which she had aged five months.

Although she suffered complications afterwards, including Graft Versus Host Disease (GVHD) where the body attacks the transplanted tissue, Ffion was well enough to go home three months later and now only needs an annual check up.

“Not only did the BMT save Ffion, but her skin is now beautiful. You’d never know she is the same child that was so desperately ill in the past,” Mrs Moseley said.

linkback url: http://www.google.com/hostednews/ukpress/article/ALeqM5im-K_CuOAjzgPmt75ziH1skVSAVA

‘She’s our little miracle’

Published Date: 17 July 2009
Dressed in pink from head to toe, two year-old Eva McLaughlin skips across the kitchen floor pushing a yellow toy shopping trolley.
“I’m going to the Spar,” chirps the blonde-haired Magilligan girl.
Seconds later, she sits by her pink toy piano and tells mum Cathy: “I’m going to play a song.”

Moments later Eva is off again, this time down the hall chatting.
Anyone meeting Eva for the first time would think she is just an ordinary toddler, full of energy and into everything.
But Eva is anything but ordinary.

“She’s a miracle, she really is,” says Cathy.

Eva was born with severe combined immune deficiency syndrome (SCID), a condition which means she had no white T blood cells which provide natural resistance against infection. Without these, infections spread and can be fatal.

At first, mum Cathy and dad Ryan had no reason to suspect anything was wrong with Eva but when their baby girl couldn’t shake coughs and infections, they knew something was wrong.

“It just wasn’t shifting,” recalls Cathy, explaining the weekly trips to the doctor.

On December 5, 2007, Eva became very ill, struggling for breath. The tot had severe pneumonia.

She was taken to the Royal Victoria Hospital in Belfast for a week where she was kept alive by a ventilator supplying her with life-saving oxygen.

“It was horrific, just complete panic,” says Cathy. “It was so hard to see and look at her in intensive care. She was just lying there.”
Miraculously, Eva was able to come off the ventilator within days. She was taken to Newcastle General Hospital for a bone marrow transplant after a match for her was found by the Anthony Nolan Trust in the USA.
“It was the only chance she had. The bone marrow transplant was the only thing she had to keep her alive,” says Cathy.

Prior to the transplant, Eva underwent eight days of gruelling chemotherapy.

“It was when her hair fell out and I picked it up from the pillow; that was just horrific,” says Cathy.

Just one day after her first birthday, Eva had a rest day. The next day she had the transplant and Cathy and Ryan were told they could not touch their child.

“They said if you kiss that child it could kill her,” recalls Cathy. “It was awful but it needed to be done but knowing I couldn’t even kiss my own daughter was hard.”

When Eva was in hospital, she lived in a tightly-controlled, 8ft x 8ft “bubble” to avoid threats to her non-existent immune system.
Almost 10 stressful months later, Eva and her parents were finally ready to go home.

“Eva was so near death and I wouldn’t wish it on anyone,” says Cathy, reflecting on the ordeal. “The doctors here and in Newcastle are miracle workers. What they did for Eva was unbelievable. It’s just unreal, just the most unbelievable experience. We handed our daughter over to the doctors and said: ‘Please cure her’.”

The trip home was an emotional one for Cathy and Ryan but the close-knit community lined the country road where they lived, wishing them well.

“Everyone was cheering and waving,” says Cathy. “Magilligan is a brilliant community. We had a brilliant reception.”

‘Lucky’

Cathy and Ryan travel to Newcastle on Monday for a check-up on Eva’s progress. They are hoping for an easing of restrictions on things she hasn’t been able to do before, like go to the beach or the zoo.
“The way Eva looks now compared to before is unreal,” says Ryan. “People can’t believe how she’s come on, running about like any other wee child. Looking back on it now with some perspective, you think, ‘We were lucky’.”

Cathy adds: “She’s a miracle, she really is.”

The family want to raise as much awareness as possible for the Anthony Nolan Trust and the Bubble Foundation and with the help of their close knit community have already raised almost £6,000 for research.
“Thank God Eva is here, and every day she’s going from strength to strength. It is a miracle,” adds Cathy.

For more information or to make a donation, go to www.anthonynolan.org.uk and www.bubblefoundation.org.uk

linkback url: http://www.derryjournal.com/journal/Shes-our-little-miracle-.5469463.jp

Baxter and Halozyme Announce Completion of Patient Enrollment in Phase III Pivotal Trial of GAMMAGARD LIQUID™ with rHuPH20 Enzyme

(Nasdaq:HALO) today announced completion of patient enrollment in the Phase III pivotal study of GAMMAGARD LIQUID [Immune Globulin Intravenous (Human) 10%] (also known as KIOVIG outside of the United States) with rHuPH20 (recombinant human hyaluronidase enzyme) for the treatment of primary immunodeficiency disorder : (PID). Patients will receive monthly
subcutaneous (SC) injections of Halozyme’s rHuPH20 with Baxter’s GAMMAGARD LIQUID : .

“The achievement of complete Phase III enrollment is an important milestone of Baxter’s work with Halozyme to offer patients more advanced treatment options,” said Hartmut J. Ehrlich, M.D., vice president of Global Research and Development for Baxter’s BioScience business.

“I am pleased with the efficiency and dedication Baxter has demonstrated toward our collaboration and their exemplary ability to manage and carry out the clinical objectives,” stated Jonathan Lim, M.D., Halozyme’s president and CEO. “Completion of patient enrollment in this Phase III registration study marks a significant and timely accomplishment for the GAMMAGARD LIQUID-rHuPH20 development program.”

This Phase III clinical trial is a prospective, open-label, non-controlled design underway in 15 centers in the U.S. and Canada. The study will evaluate the safety and efficacy of GAMMAGARD LIQUID administered SC with rHuPH20 in the prevention of acute serious bacterial infections over 12 months and will also assess pharmacokinetic parameters of SC GAMMAGARD LIQUID with rHuPH20 compared to intravenous (IV) administration of GAMMAGARD LIQUID alone. Patient Quality of Life (QOL) parameters will also be measured. Subcutaneous administration of GAMMAGARD LIQUID with rHuPH20 in this investigational study will determine if it will allow PID patients to receive a full monthly dose in a single injection site in the home setting. GAMMAGARD LIQUID is currently only approved for IV administration. Additional information about this Phase III study can be found at clinicaltrials.gov : .

About GAMMAGARD LIQUID

GAMMAGARD LIQUID is indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity.

These include but are not limited to congenital X-linked agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.

Important Safety Information

GAMMAGARD LIQUID is contraindicated in patients with known anaphylactic or severe hypersensitivity responses to Immune Globulin (Human).

Patients with severe selective IgA deficiency (IgA < 0.05 g/L) may develop anti-IgA antibodies that can result in a severe anaphylactic reaction.

Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable in at risk patients.

GAMMAGARD LIQUID is made from human plasma. It may carry a risk of transmitting infectious agents, e.g. viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. Some viruses, such as B19V or hepatitis A, are particularly difficult to remove or inactivate.

GAMMAGARD LIQUID should only be administered intravenously.

Immediate anaphylactic and hypersensitivity reactions are a remote possibility.

IGIV products can contain blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin causing a positive direct antiglobulin reaction and, rarely, hemolysis. Hemolytic anemia can develop subsequent to IGIV therapy due to enhanced red blood cell sequestration.

There have been reports of noncardiogenic pulmonary edema (Transfusion Related Acute Lung Injury [TRALI]) in patients administered IGIV.

Thrombotic events have been reported in association with IGIV. The potential risks and benefits of IGIV should be weighed against those of alternative therapies.

Aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with GAMMAGARD LIQUID treatment.

Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae.

For full prescribing information, please visit: www.baxter.com/products/biopharmaceuticals/downloads/gamliquid_P .. :

About Baxter

Baxter International Inc., through its subsidiaries, develops, manufactures and markets products that save and sustain the lives of people with hemophilia, immune disorders, infectious diseases, kidney disease, trauma, and other chronic and acute medical conditions. As a global, diversified healthcare company, Baxter applies a unique combination of expertise in medical devices, pharmaceuticals and biotechnology to create products that advance patient care worldwide.

About Halozyme Therapeutics, Inc.

Halozyme is a biopharmaceutical company developing and commercializing products targeting the extracellular matrix for the endocrinology, oncology, dermatology and drug delivery markets. The company’s portfolio of products and product candidates is based on intellectual property covering the family of human enzymes known as hyaluronidases and additional enzymes that target the extracellular matrix. Halozyme’s Enhanze ™ Technology is a novel drug delivery platform designed to increase the absorption and dispersion of biologics. The company has key partnerships with Roche to apply Enhanze Technology to Roche’s biological therapeutics for up to 13 targets and with Baxter BioScience to apply Enhanze Technology to Baxter’s biological therapeutic compound, GAMMAGARD LIQUID ™ . The product candidates in Halozyme’s research pipeline target multiple areas of significant unmet medical need. For more information visit www.halozyme.com : .

Safe Harbor Statement

In addition to historical information, the statements set forth above include forward-looking statements (including, without limitation, statements concerning the GAMMAGARD-rHuPH20 clinical development program) that involve risk and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. The forward-looking statements are also identified through use of the words “believe,” “enable,” “may,” “will,” “could,” “intends,” “estimate,” “anticipate,” “plan,” “predict,” “probable,” “potential,” “possible,” “should,” “continue,” and other words of similar meaning. Actual results could differ materially from the expectations contained in forward-looking statements as a result of several factors, including regulatory approval requirements and competitive conditions. These and other factors that may result in differences are discussed in greater detail in each company’s reports on Forms 10-K, 10-Q, and other filings with the Securities and Exchange Commission.

Baxter Media ContactsChris Bona, 847-948-2815Laura
Grossmann, 847-948-3026orBaxter Investor ContactsMary
Kay Ladone, 847-948-3371Clare Trachtman, 847-948-3085orHalozyme
ContactRobert H. Uhl, Senior Director, Investor Relations,

858-704-8264 ruhl@halozyme.com : mailto:ruhl@halozyme.com

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DellaCamera Claims Enzon CEO Can (Almost) Never Be Fired

DellaCamera Capital gathered what it claimed was more than 50 percent of Enzon’s shareholders into a hotel conference room in Midtown New York today to make the case for staging a coup against CEO Jeff Buchalter.

The presenter, DellaCamera research chief Richard Mansouri, dropped some interesting new nuggets into the debate over whether Buchalter should be removed by his shareholders (the stock is down by more than 50 percent over the last five years). Among them:

* Buchalter’s contract requires an unusual 12 months’ notice if the company wants to fire him — and as he’s also contractually required to be Enzon’s board chairman, it is thus virtually impossible for the board to remove him. “We’ve never seen anything like this,” Mansouri said. While dual CEO/chairman roles often create unaccountable “imperial” bosses with built-in conflicts of interest, “The fact that it is contractually mandated is even worse,” he said. Buchalter gets about $5 million a year in compensation even though his company only makes $197 million in revenues.
* Buchalter announced he was exploring the sale of his specialty pharma division in August 2008, and then concluded that effort with no sale in November. No explanation or detail has been offered as to exactly why that effort failed, Mansouri said. “We are not at all satisfied with this lack of information.”
* Enzon has gone through $55 million in “other” R&D costs on “discontinued” products since 2005, and that “other” expenses are the company’s largest R&D cost.

“Something is wrong. Something is very wrong here,” Mansouri concluded.

The audience was subjected to this PowerPoint slideshow, much of which rehashed the case for change that Ralph DellaCamera’s (pictured above) group previously made in a June 1 SEC filing. Get BNET’s take on the back story here.

The chief weakness in the DellaCamera case is that the group won’t say who it thinks should replace Buchalter (pictured below) and nor will it reveal what it believes the company’s strategy should be. “We don’t have any other agenda,” Mansouri said.

This hole will become more important as it gathers shareholder support, because despite its flaws Enzon isn’t a complete disaster: It made $6 million in profit on $48 million in revenue in Q1, both small increases from the year before. Shareholders faced with a stay-the-course plan from Buchalter and no plan at all from DellaCamera might be forgiven for sticking with the devil they know.

In the wings is Carl Icahn, who owns 7.8 percent of Enzon. Icahn just succeeded in putting two supporters on Biogen’s board and two on Amylin’s board. He already has one guy on Enzon’s board.

The event set the stage for an exciting battle, but don’t get too excited: When pressed by BNET, Mansouri all but admitted that the historical success rate of shareholder votes to remove CEOs is zero.

linkback url: http://industry.bnet.com/pharma/10002625/dellacamera-claims-enzon-ceos-contract-says-he-can-almost-never-be-fired/

Biotech Pioneer

Life Science Leader, May 2009
Written by: Cliff Mintz

Dr. Abraham Abuchowski, COO and president of Prolong Pharmaceuticals, grew up on a chicken farm in rural Vineland, NJ. Realizing that chicken farming wasn’t in his future, Abe attended Rutgers University, receiving a B.S. degree in 1970 and Ph.D. in biochemistry in 1975. During his thesis work, Abe developed a novel protein delivery system called PEGylation, which involved chemically linking the polymer polyethylene glycol (PEG) to proteins. He continued his work on protein PEGylation at Rutgers, first as a postdoctoral fellow, then as research assistant professor and Leukemia Society scholar until 1983, when he left to form Enzon, one of New Jersey’s first publicly traded and profitable biotechnology companies.

During his 13-year tenure as president and CEO of Enzon, Abe and his team optimized protein PEGylation, which led to the development of the first three FDA-approved PEGylated products. Recognizing the need for biotechnology advocacy, Abe formed and served as the first chairman of the Biotechnology Council of New Jersey in 1994, which still exists today and has helped grow the New Jersey biotechnology industry. Abe left Enzon in 1996 and spent the next nine years in semiretirement — playing with his hobbies (woodworking, aviation, auto mechanics, and feeding chickens) on his farm in northwestern New Jersey and helping would-be entrepreneurs start up new biotechnology companies. In 2002, realizing that protein PEGylation still had enormous potential for the biopharmaceutical industry, he formed Prolong Pharmaceuticals, a company that focuses on developing novel PEGylated protein-based products.

Abe, who attributes his entrepreneurial success to martial arts training and participation in the McDonald Corporation management trainee program, is a biotechnology industry pioneer and is often referred to as the “Father of PEGnology.” Over the past 25 years, he has received numerous scientific and business achievement awards — most recently, the Dong Sung Pharmaceutical Award in Seoul, Korea for the development of PEGylation technology and the USC Marshall School of Business Outstanding Achievement Award.

I had an opportunity to catch up with Abe, who has two new PEGylated protein products in clinical development, to chat about the events that led to the development of protein PEGylation, his views on entrepreneurship, and the current state of the biotechnology industry.

How did you come up with the idea for protein PEGylation?

Abuchowski: My thesis advisor, Dr. Frank Davis, long believed that chemical conjugation of polymers to proteins may help alleviate some of the deleterious and potentially life-threatening side effects commonly associated with nonhuman proteins like insulin (isolated from animal sources) that were routinely used in the 1970s. Frank reasoned that the addition of an inert polymer to a protein might dampen host immune responses and reduce the side effects following the parenteral administration of nonhuman proteins. Because this was Frank’s pet project, he required all graduate students who wanted to work with him to “take a crack at protein conjugation.” Despite knowing that many graduated students had failed before me, I enthusiastically agreed to work on the protein conjugation project — I was young, brash, and naively overconfident at the time!

While there were many potential conjugation candidates to choose from, Frank decided on PEG mostly because it was a ubiquitous substance found in a wide variety of cosmetics, ointments, suppositories, and even food products. Further, and perhaps more importantly, PEG was generally regarded as safe by the FDA, which meant if we were successful, regulatory approval of PEG-protein conjugates would be less challenging. After developing some rudimentary protein conjugation chemistries, I began PEGylating any proteins that I could get my hands on. I PEGylated more proteins than I can remember. After creating the PEG-protein conjugates, I tested them (and their un-PEGylated counterparts) for immunogenicity, turnover rates, and circulating half–life times in a wide variety of standardized animal models that were being used at the time. And, as predicted, the PEGylated proteins were virtually non-immunogenic, had lower turnover rates, and exhibited vastly improved circulation times as compared with un-PEGylated controls.

Because at the time that we developed protein PEGylation, the use of proteins as drugs was very limited — the biotechnology industry was just coming to fruition — there wasn’t much excitement or commercial interest in our technology. Most scientists generally regarded PEGylation as an anachronistic technology. Nobody realized at the time that protein PEGylation would help to improve the characteristic and delivery of virtually any protein-based biotechnology product.

Why did it take over 25 years for PEGylation to be accepted as a bona fide protein delivery technology?

Abuchowski: Before I began working on protein PEGylation, many high-powered academic laboratories had diligently tried (and failed) to chemically modify proteins to reduce their immunogenicity — a vexing problem that severely limited the use of nonhuman therapeutic proteins in the 1970s. Also, at the time, many prominent scientists thought that the newly emerging field of genetic engineering could be used to overcome the immunogenicity problems that plagued nonhuman, protein-based therapies. Consequently, many of my peers mistakenly viewed protein PEGylation as a competing (rather than an adjunctive) technology and refused to acknowledge our work.

Despite several publications and reams of scientifically sound data, most scientists in the late 1970s refused to believe that protein PEGylation really worked! In retrospect, I suspect many of them refused to believe that a young chicken farmer from New Jersey could accomplish something that many of them failed to do! Nevertheless, I was convinced that protein PEGylation had the potential to revolutionize the emerging biotechnology industry. Further, I realized, unlike my colleagues, that I didn’t have to discover new proteins to make drugs — I could simply PEGylate existing, well-characterized ones that seemed like good drug candidates — a strategy that took others over 20 years to recognize.

After leaving Rutgers in 1983, I was determined to commercialize protein PEGylation. However, because pharma wasn’t interested in the technology, I had to form my own company (Enzon) to confirm PEGylation as a reliable protein delivery system. It was a huge gamble because there were many naysayers and nonbelievers in the scientific community who, I think, were hoping that I would fail. To overcome persistent doubts about the technology, we decided to PEGylate a protein that could be used to treat an otherwise fatal disease — thinking, that if we were successful, FDA would have no choice but to approve the drug. This resulted in development of Adagen, the first and only approved treatment for severe combined immunodeficiency disease (SCID). Interestingly, Adagen was approved in 1990 on the strength of data we collected from eight patients with SCID.

Because Adagen was approved as an orphan drug, the pharmaceutical industry continued to doubt the commercial and financial potential of protein PEGylation. To overcome these lingering doubts, we developed Oncospar (pegaspargase), an anticancer treatment for acute lymphocytic leukemia (ALL). ALL was an obvious choice to showcase the utility of protein PEGylation because patients with ALL frequently developed immune hypersensitivity to asparaginase, the only recognized ALL treatment at the time. PEGylating asparaginase rendered the enzyme nonimmunogenic, eliminated the hypersensitivity reaction, and brought asparaginase-refractory patients with ALL into remission. Oncospar received FDA approval in 1994.

While Enzon was able to gain approval for two PEGylated products in 11 years — a remarkable feat for a biotechnology startup — the commercial potential of protein PEGylation wasn’t fully realized until 2001, when Schering-Plough and Enzon introduced PEG-Intron as a treatment for hepatitis C infections. Within a year, PEG-Intron had captured 65% of the hepatitis C market and reached about a billion dollars in sales. Protein PEGylation had finally hit the big time!

What advantages does protein PEGylation offer over other potential protein delivery technologies?

Abuchowski: PEGylated proteins are generally nonimmunogenic, exhibit increased circulating half-lives (i.e. are longer acting), require fewer injections for therapeutic efficacy, have vastly improve tolerability and safety profiles, are resistant to proteolytic digestion, and are readily excreted in urine and feces. Sometimes, when the wrong chemistry is used to conjugate PEG to a protein, PEGylation may interfere with the biological or therapeutic activity of the molecule. Aside from that, I can’t easily think of any negative attributes associated with the technology. Believe me — I have tried for over 30 years to find problems with the technology, but I haven’t been able to!

As far as I know, there aren’t any competing FDA-approved protein delivery technologies on the market right now. There are several new delivery systems being developed, including several that use human serum albumin and other human endogenous proteins as delivery vehicles. To date, the FDA has approved eight PEGylated therapeutic proteins — most of which are multibillion-dollar blockbuster products. Further, there may be as many as 30 PEGylated proteins in clinical development. I think it is safe to say that protein PEGylation has become the gold standard of the protein delivery industry right now.

There are currently only a handful of companies like Amgen, Roche, Nektar, Schering-Plough, and Enzon that have taken advantage of PEGylation to deliver protein-based drugs. Why haven’t more biotech companies leveraged the power of protein PEGylation?

Abuchowski: As most scientists will tell you, there is a substantial amount of art — not just technical prowess — when it comes to optimizing scientific methods. While many of the numerous PEGylation chemistries out there are straightforward and easy to use, the key to creating a successful PEGylated product is choosing the best chemistry and the right-sized PEG that will impart the desired biological characteristics on a product. At present, there are numerous PEGylation chemistries and multiple different molecular species of PEGs that can be used to PEGylate proteins. The learning curve is steep for protein PEGylation, and unless somebody on your development team has prior experience with it, PEGylation can be a real hit-or-miss exercise.

In my opinion, many companies that try to PEGylate proteins spend too much time studying PEGylation chemistry and not enough time thinking about ways to optimize the PEGylation process for scale-up and manufacturing purposes. The days of charging 10 times the development costs of a product are gone — it is all about manufacturing efficiencies and pharmacoeconomics (the scientific discipline that compares the value of one pharmaceutical drug or drug therapy to another) now. It is no longer economically feasible for companies operating on slim margins to use a reaction that consumes 90% of your starting materials and yields only 10% product. Further, the manufacturing process has to be facile and lean. This is because the pharmaceutical operators who are charged with manufacturing a product are typically not Ph.D.s but people with high school and associate degrees. Processes need to be uncomplicated, robust, and scalable to be effective.

My almost 30 years in the biotechnology industry has taught me that the most critical step in creating a product is not science but the manufacturing and formulation processes. This is because patents that originally protect the scientific aspects of a product typically expire early in a product’s life cycle. Patents that are developed around manufacturing, formulation, and delivery are the ones that typically extend the life of a product and help to protect lucrative blockbuster drug franchises. A great example of this is Amgen’s EPO franchise. The composition of matter patents for EPO expired in 2004, but additional formulation and manufacturing patents will protect the franchise through 2017. I believe that the companies that understand manufacturing and commercialization will always trump companies that may have scientifically superior products.

What other products may benefit from protein PEGylation?

Abuchowski: Any protein-based product could possibly benefit from PEGylation. However, before PEGylating a protein, it is important to understand its biology and intended use. For example, early on, I PEGylated insulin and learned that increasing its circulation time was not such a good idea because it can easily lead to hypoglycemic shock. I think that you may see an increased use of PEGylation in single-chain antibodies, RNAi and oligonucleotide products, and even in nonviral-based gene delivery technologies.

While I believe some proteins can be delivered via the nasal or oral routes, these routes of administration are typically less efficient and not as cost-effective as parenteral delivery. That said, I think parenteral administration of protein-based drugs is here to stay.

What is the future of PEGylation in the biopharmaceutical industry? Are there any competing protein delivery technologies that may supplant it?

Abuchowski: I think that protein PEGylation has finally hit its stride, and that we will see more applications of the technology to biotechnology products in the future. There are many prospective therapeutic proteins out there that can’t be transformed into drugs because they may be too toxic, have poor circulating half-lives, or are turned over too rapidly following injection. PEGylation affords biopharmaceutical manufacturers an opportunity to increase a protein’s circulating half-life, improve its safety and tolerability profiles, and lower the cost per patient without sacrificing therapeutic efficacy. I think in today’s fast-paced and highly competitive market, the question is no longer whether or not to PEGylate, but when!

There are several companies working on new parenteral delivery technologies for biotechnology drugs. Most of these involve creation of fusion proteins, which genetically link a human carrier protein like serum albumin to a protein of interest. While these technologies are promising, they are more costly than PEGylation, and to my knowledge, none has been successfully scaled to commercial manufacturing levels. It is noteworthy that PEGylation became the de facto drug delivery system for protein-based drugs only after the introduction of PEG-Intron in 2001. This means it took the pharmaceutical industry about 19 years from the time I discovered the technology to recognize protein PEGylation’s utility and commercial potential. I suspect it may take as long or longer for a competing technology to supplant PEGylation as the gold standard for parenteral protein-based drug delivery.

You formed Enzon in the mid-1980s before there was a biotechnology industry to speak of and then formed Prolong Pharmaceuticals 20 years later when biotech had finally hit its stride. Many new entrants into the biotechnology industry contend that the drug commercialization paradigm has changed, and that it is much harder to get drugs approved today than in the past. What are your thoughts on these assertions?

Abuchowski: When I started Enzon there were no CROs, CMOs, or any other type of third-party vendors to help support operations. Consequently, we had to become a vertically integrated biopharmaceutical company so we could develop our products, manufacture them, and then sell them. While it was a lot of grueling, hard work, I was fortunate to have personally experienced each stage of the biopharmaceutical drug development paradigm, ranging from drug discovery through clinical development and marketing and sales. These experiences provided me with skill sets that have served me well over my 30 years in the biotechnology industry and enabled me to form Prolong in 2003 with much less money than it took to start Enzon. That said, the biotechnology industry landscape is much different than it was 25 years ago.

Almost every aspect of drug development can now be outsourced to competent and reputable third-party vendors. Consequently, there is absolutely no need for biotechnology companies to become vertically integrated today. CEOs who are intent on vertical integration are, in my opinion, wasting shareholders’ money and stroking their own egos. This is why so many biotechnology companies have failed and will continue to fail. In today’s world, companies are now expected to do a lot more with much less.

I don’t think gaining regulatory approval and commercializing biotechnology drugs is more difficult than it was in the 1980s. There is certainly more competition, but I think that is good for the industry as whole. While I was at Enzon, I worked very closely with FDA regulators and managed to get two drugs approved in 11 years. However, there is no question that, over the past decade or so, the relationship between the biotechnology industry and the agency has become very strained. Many biotechnology industry CEOs are angry and frustrated because the FDA isn’t approving new drugs as quickly as it has in the past. This has resulted in an intensive lobbying effort to relax the drug approval process. While this may lead to quicker drug approvals (and more money for drug company CEOs and their shareholders), I don’t think it would be in the best interest of the American public.

There is no question that the FDA could be improved and operated more efficiently and effectively. The agency has suffered from poor leadership, inadequate funding, and personnel shortages for the past eight years or so. However, I do believe the people who work at the FDA have the best interests of the public in mind.

Will the biotechnology industry be able to weather the current economic downturn?

Abuchowski: Yes, but it will be painful for inefficient companies and those who have no products in clinical development or on the market. Like others, I believe that about 60% of existing biotechnology companies will fail or be bought by big pharma over the next few years. This is because most of these companies are operating on venture capital money (which is getting harder to find) and haven’t been able to develop any products despite “being in business” for five or more years. Ironically, the venture capitalists may turn out to be their own worst enemies because they funded too many ill-conceived startups hoping to get quick returns on their investments without fully understanding the industry. The most important thing I learned about biotechnology companies is that while science and patents may be important, the success or failure of a biotechnology company invariably hinges on solid regulatory, commercialization, and manufacturing strategies. Companies that lack these are doomed to fail. I don’t expect this paradigm to change anytime soon as the biotechnology industry continues to evolve in the 21st century.
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