DENVER -- At least eight global biotech companies are racing to find an effective treatment for Oral Mucositis, which impacts roughly 40% of all patients receiving cancer treatments, including about 400,000 Americans each year.

The stakes are extremely high. 

•    For patients undergoing chemotherapy and/or radiation treatment, it could spell the end of painful lesions of the mouth, tongue and throat that leave many people unable to eat, speak and continue their life-saving treatments.

Oral mucositis related infections frequently require hospitalization and in some cases lead to death.

•    For oncologists it could provide the ability to administer newer, more effective chemotherapeutic agents without concern for the harsh side effects that cause some patients to halt treatments.  Eliminating oral mucositis symptoms would allow doctors to focus their full attention on the underlying cancer.

•    Health insurance companies would see the cost of care reduced significantly, as cancer patients avoid the need for oral mucositis-related medical intervention and hospitalizations.

•    For the successful biotech companies, the global market for oral mucositis treatment and/or prevention could reach $5 billion annually.  That represents a huge worldwide market to be served by one or more successful biotech companies, all of whom are currently comparatively small in size.

Despite its prevalence, Oral Mucositis has attracted scant media attention.  At present, the most common treatments for oral mucositis are “home-made” remedies mixed by oncologists or cooperative pharmacists.  But the effectiveness of these concoctions is limited and none of them has been shown to prevent oral mucositis.

Companies with oral mucositis treatments in the pipeline or already on the market include:

Access Pharmaceuticals (OTC: ACCP)
Avaxia Biologics (Burlington, MA)
Biotec Pharmacon (Oslo Stock Exchange: BIOTECH
EpiCept Corp. (NASDAQ: EPCT)
EUSA Pharma (UK)
Helsinn (Lugano, Switzerland)
The GI Company (Framington, MA)
SciClone Pharmaceuticals (NASDAQ: SCLN)

Veteran BusinessWeek investment columnist, Gene Marcial, writes today that Access Pharmaceuticals, maker of an FDA-approved treatment for Oral Mucositis, could be an attractive takeover target.

"As major pharmaceuticals seek companies with a pipeline of promising drugs to augment their own depleting inventories, some pros bet that one target will be Access Pharmaceuticals (ACCP), now at 2.85 a share," Marcial writes in his Inside Wall Street column.

The columnist cites a securities analyst with Griffin Securities, Keith Markey, as estimating that Access Pharma's MuGard treatment for oral mucositis is by itself worth more than the total current market value of Access.  MuGard is already on sale in Europe and Access plans to begin manufacturing the treatment before the end of the year in the United States.  The FDA approved MuGard in 2007.

Two other cancer drugs in development by Access, Prolindac and Thiarabine, make the company even more attractive, Marcial notes.

An expert on Oral Mucositis (OM) and its debilitating affects on patients receiving cancer treatment forecast that the number of annual cases may increase due to the more frequent usage of newer chemotherapeutic agents.  Currently, approximately 400,000 Americans develop OM each year.

OM frequently results in very painful open sores in the mouth and throat that often interfere with a patient's ongoing chemotherapy or radiation treatments.  Oral mucositis also makes cancer patients prone to life-threatening infections and sometimes OM complications result in death.

Douglas Peterson, DMD, Ph.D, who has researched the prevention and treatment of mucositis in at-risk cancer populations for about 17 years, said in a recent news release that as clinical oncology practices embrace newer, more effective treatments, "the incidence and severity of mucositis may increase" because these cancer-fighting agents have significant oral toxicities. 

Dr. Peterson is co-author of a peer-reviewed article in this month's edition of the Journal of Clinical Oncology (see OMN article below).  His comments appear in a news release from The GI Company, where Dr. Peterson has served on the scientific advisory board since December 2007.

"Management of clinically significant oral mucositis in cancer patients currently represents a significant challenge," Dr. Peterson says in the September 10th news release.  "...there is a clear, unmet medical need for developing this targeted therapeutic with such an excellent safety profile," he added. 

Dr. Peterson was referring to a clinical compound produced by The GI Company, known as rhITF (recombinant human Intestinal Trefoil Factor), which in the Journal of Clinical Oncology investigation showed statistically significant Phase II results in preventing oral mucositis in colorectal cancer patients.

In explaining the causes of Oral Mucositis, The GI Company notes that "cytotoxic therapies are used to kill cancer cells, but they also indiscriminately kill other fast-growing normal cells such as those lining the inside of the mouth and throat." 

The GI Company is one of a growing list of global biotech companies that is developing treatments and preventative applications for oral mucositis. 

Dr. Peterson has published more than 100 peer-reviewed scientific papers.  He currently serves as Professor of Oral Medicine in the Department of Oral Health and Diagnostic Sciences in the School of Dental Medicine, as well as Chair of the Head and Neck/Oral Oncology Program at the University of Connecticut Health Center. At the time he was appointed to the GI Company science panel in 2007, the company noted that he worked as a Special Government Employee for the Food and Drug Administration pertaining to OM and the development of related drugs.

Photo: Douglas E. Peterson, DMD, Ph.D - University of Connecticut Health Center

A peer-reviewed article published this month in the Journal of Clinical Oncology reported positive results for colorectal cancer patients who used an oral spray to combat the effects of moderate-to-severe Oral Mucositis (OM).

The results were reported by The GI Company, whose lead clinical compound, rhITF (recombinant human Intestinal Trefoil Factor) was given to patients in the double-blind, placebo-controlled study. 

"Results of this Phase II study demonstrate that rhITF oral spray formulation is safe and highly effective in the prophylaxis of chemotherapy-induced OM in colorectal cancer patients," GI Company said in a news release.  "Patients also exhibited high compliance in dosing administration" and reported no concerns pertaining to the taste of the oral spray.

The GI Company has an exclusive license for the rhITF technology platform from Massachusetts General Hospital (Mass Gen).  Dr. Daniel K. Podolsky, co-chairman of the GI Company Board, is Mallinkrodt Professor of Medicine and Chief of Gastroenerology at Mass Gen  and Harvard Medical School.  Dr. Douglas Peterson, first author of the rhITF Journal of Oncology publication is a member of the GI Company's scientific advisory board.


The GI Company said it is looking for investors to help advance its oral spray into clinical trails and through the regulatory approval process.  The company has retained merchant bankers, Burrill & Company, to help it identify "global transaction partners."

Dr. Peterson, the lead author, described the study's results as "highly encouraging."  The company noted that the differences between the rhITF groups and placebo "were highly statistically significant."

Ninety-nine colorectal cancer patients participated in the study.  Patient diaries were used to corroborate the measurement of Oral Mucositis following both the World Health Organization scoring system and the Oral Mucositis Assessment Scale.

Based in Framingham, Massachusetts, The GI Company describes itself as a clinical-stage biotechnology company highly specialized at developing drugs to treat gastrointestinal and related diseases.  The company's lead clinical candidate is rhITF.  To date, The GI Company has raised more than $20 million through a private equity financing consortium.

Access Pharmaceuticals, maker of the FDA-approved MuGard for the treatment of Oral Mucositis, has hired a leading commercial manufacturer to begin producing the oral wound rinse as early as the fourth quarter of this year.

Initial batches of the U.S.-made MuGard will be used in one or more market seeding studies that Access plans to conduct following protocols that the company is currently developing, Access said in a news release.  Access entered into an agreement with Accupac, Inc., to serve as its commercial manufacturer of MuGard in North America.  Accupac makes, fills and packages a wide range of consumer commodity, over-the-counter and prescription products for the world's largest pharmaceutical and consumer products companies, the release notes.

"Establishing our relationship with Accupac, a leader in liquid contract manufacturing, is critical to our successful commercialization of MuGard," said Jeffrey B. Davis, Access' President and CEO.  Access notes that the market for the treatment of oral mucositis is estimated to be in excess of $5 billion globally when all patients undergoing chemotherapy and radiotherapy are counted.

The company's MuGard is a ready-to-use rinse that forms a protective coating over the oral mucosa when swirled gently around the mouth.  It is already being marketed in the United Kingdom, Germany, Italy, Norway and Greece by Access' partner, SpePharm.

"In a comparison of cancer patients receiving standard oral mucositis care with those patients receiving MuGard, MuGard has been shown to significantly reduce the incidence and severity of the debilitating side effect of radiation treatment and chemotherapy," according to the Access release.

Access, an emerging biopharmaceutical company, is based in Dallas.  It develops and commercializes propriety products for the treatment and supportive care of cancer patients.

Photo:  Jeffrey B. Davis, Access Pharmaceuticals

Two companies promoting their treatments for Oral Mucositis plan to make presentations this week before Wall Street investors. 

The outreach is a reminder that medical advancements often require large amounts of capital, which in turn means that small pharmaceutical companies not only must master research and development, but marketing and fund-raising as well.

Beginning September 9 and running through September 11, investment bank Rodman & Renshaw will hold its Annual Global Investment Conference in New York.  This year, the R&R event will include presentations from more than 500 companies that both present to and meet one-on-one with many of the institutional investors, venture capitalists and private equity managers who attend.

For small biotech and pharmaceuticals companies, the Rodman & Renshaw forum is one of the most important investor forums of the year. This year, according to R&R, as many as 3,500 attendees are expected.  Dr. Alan Greenspan, former head of the Federal Reserve System, is a keynote speaker.

On Friday, Jeffrey B. Davis, president and CEO of Access Pharmaceuticals, is scheduled to provide a corporate overview and discuss the company's product opportunities.  These include MuGard, an FDA-approved advancement in the treatment of oral mucositis which is currently rolling out in Europe and will be available in the United States in 2010. 

"We think MuGard's commercial value is compelling, based on its use in the large, underserved oncology market," wrote Griffin Securities in a July 30th report.  "[MuGard's] formulation is well liked by patients, as it has a pleasing flavour and may be swallowed without concern."

On Thursday, Friedhelm Blobel, president and CEO of SciClone Pharmaceuticals, will make a presentation at the R&R conference.  Among the products in SciClone's pipeline is SCV-07, which the company says is "in a phase 2 trial for the delay of onset of severe oral mucositis in patients receiving chemoradiation therapy for the treatment of cancers of the head and neck."

A live link to both Access Pharmaceuticals and SciClone's sessions are available via links from their respective web sites.

There is little doubt that before his death from a malignant glioma on August 25, Senator Edward M. Kennedy suffered from oral mucositis, a highly common side effect of those being treated with radiation and chemotherapy for brain cancer.  

First diagnosed in May 2008 after a brain biopsy revealed a tumor in the his left parietal lobe, the senator underwent surgery at Duke Medical Center in North Carolina in June 2008 followed by proton beam radiation therapy and chemotherapy at Massachusetts General Hospital.

Many of the specifics of the senator’s condition and treatments have never been revealed and may never be.

But medical experts have surmised that the senator, the last surviving brother of the legendary Kennedy dynasty that included President John F. Kennedy and Senator Robert F. Kennedy, likely underwent at least six weeks of radiation.

Writing in the July 27, 2009 edition of Newsweek magazine, Kennedy himself revealed, “I’ve undergone many rounds of chemotherapy and continue to receive treatment.”  As CNN.com notes in a story posted after the senator’s death:  “During the [weeks] of radiation, a patient typically would take an oral chemotherapy drug called Temodar at a low dose every day…Then, a month-long break is followed by at least six months of Temodar at a higher dose.”

With very few exceptions, all head and neck cancer patients who are treated with radiation and chemotherapy develop oral mucositis, a side effect that ranges from mild – redness and tolerable sores of the mouth and throat, to severe – open sores so painful and infected that they require tube feeding, hospitalization and in some cases result directly in death.

While Kennedy’s illness calls attention to brain cancer and advances in its treatment, the degree to which the senator was impacted by oral mucositis remains a mystery.  

In the CNN.com article, Dr. Donald O’Rourke, associate professor of neurosurgery at the University of Pennsylvania School of Medicine, says there have been a “recent explosion” of technology, such as surgical and imaging techniques, that have helped the survival rate of brain cancer victims.

However, there does not seem to have been a single article in the mainstream news media that likewise notes that cancer patients, such as Senator Kennedy, now also have more, highly effective methods of treating and even preventing some of the harshest side effects of cancer treatments, such as oral mucositis.

Perhaps, with time, the Kennedy family will disclose just how the senator coped with his own bout of oral mucositis, assuming that he did suffer from it prior to his death.  The annual incidents of oral mucositis in all cancer patients vastly outnumbers the number of brain cancer victims.

Painful lesions and related infections in the mouth, on the tongue and in the throat are a common side effect of cancer treatments. If you have these, you are far, far from alone.
 
Sometimes the condition, known as oral mucositis, is so painful that cancer patients are unable to eat and/or unable to continue their life-saving treatments until the pain subsides. 

Drs. Nathaniel S. Treister and Sook-Bin Woo, both of Harvard School of Dental Medicine, estimate at emedicine that 400,000 cancer patients each year wrestle with oral mucositis.  More specifically, three-quarters of patients who receive so-called 'conditioning regimens' in preparation for hematopoietic cell transplantation (HCT) and four-out-of-every-ten patients who are treated with chemotherapy will get oral mucositis.  For patients being treated for head and neck cancer, the correlation with oral mucositis is virtually 100%.

The good news is that in the United States and around the world, a variety of promising treatments for oral mucositis are either already on the market or in late stage development. In addition, some of the treatments hold the promise of also preventing the occurrence of oral mucositis in the first place.

A 2008 survey cited by EUSA Pharma, one of the makers of oral mucositis treatments, found that 90% of those who suffer oral ulcerations and inflammation as a result of cancer therapy feel it adversely affects their quality of life.  The most common symptoms listed by the 427 survey respondents were redness and swelling (54 percent), burning pain (47 percent), difficulty opening one's mouth (46 percent), difficulty speaking (40 percent) and tooth and/or gum disease (35 percent).

Surprisingly, only about half of those suffering from oral mucositis are formally diagnosed with it.  Worse, many health care providers remain unaware of the emergence of effective treatments.

There are an abundance of reasons for patients, their families and their health care providers to educate themselves about oral mucositis and remain informed on the progress being made in the treatment and prevention of this condition.  When managed early and properly, patients can spare themselves unnecessary pain, treatment disruputions and potentially life-threatening complications.

Health professional and insurers who are keyed into the latest developments pertaining to oral mucositis can reduce or eliminate the severity of the side effect, thus enabling the medical team to give their full attention to addressing the underlying cancer.  Patients who never develop oral mucositis or are quickly and effectively treated for it, reduce the costs of their treatments by untold thousands of dollars.

The Oral Mucositis Newswire will endeavor to keep the public abreast of all pertinent developments pertaining to this common condition and educate patients, their families, health care professionals, insurers and policymakers of related news.

Resources:

• Chemotherapy-Induced Oral Mucositis by Drs. Treister and Woo
• Access Pharmaceuticals Inc. (Makers of MuGard)
• EKR Therapeutics Inc. (Makers of Gelclair)
• EUSA Pharma Inc. (Makers of Caphosol)

Harvard School of Dental Medicine Photo: Dr. Nathaniel S. Treister

The August 3, 2009 edition of ONCOLOGY Nurse Edition features an article that recounts the difficult experiences of two cancer patients who developed oral mucositis.

Written by Marilyn L. Haas (PhD, CNS, ANP-BC), a nurse practitioner in Asheville, North Carolina, "Oral Mucositis in Radiation/Chemotherapy: Treatment Similarities" tells the case stories of "Mrs. S," a 64-year-old with

squamous cell carcinoma of the anal canal and "Mrs. J," a 48-year-old registered nurse with squamous cell carcinoma of the throat.

"When OM interfered with their eating, comfort, and overall quality of life, depression was evident to their family members"

Mrs. S. waited months and months, despite pain and periodic rectal bleeding, to see a doctor.  She was recently divorced and had financial concerns.  When she was finally examined, her physicians diagnosed the cancer and prescribed both chemotherapy and radiation treatments.  The side effects were unpleasant, including hair loss, neutropenia, a skin reaction in the perineal area and oral mucositis.

The combination of perineal pain and OM was so debilitating, that Mrs. S. wanted to stop her chemoradiation after having completed 22 of her scheduled 33 fractions of radiation, Dr. Hass reported.

Mrs. J., the registered nurse, worked in the hospital emergency room and found herself in the unpleasant position of becoming a patient.  "One day at work, she felt a lump on the side of her neck," writes Dr. Haas.  Eventually, a biopsy revealed the cancer and Mrs. J. was given concurrent chemotherapy and radiation.

At first, Mrs. J. experienced dry mouth and loss of taste.  Later, mid-treatment, she required a feeding tube and had to hold off on her last dose of chemotherapy because of unpleasant side effects. 

"When OM interfered with their eating, comfort, and overall quality of life, depression was evident to their family members," Dr. Haas wrote. 

Dr. Haas concludes that patient education is an important part of the management of patients who develop OM, as are visits with a qualified dentist before, during and after treatment.  She adds: "Oncology nurses need to continue to seek evidence-based interventions that can alleviate OM and its potential complications."

[Note:  The ONCOLOGY article discloses that Dr. Haas serves as a consultant for EUSA Pharma Inc..  Dr. Haas works for Mountain Radiation Oncology.]

Resources:

• ONCOLOGY (A Monthly Journal)
• Mountain Radiation Oncology
• American Association of Oral and Maxillofacial Surgeons (AAOMS)

C

Cytotoxic

Any agent or process that kills cells, such as chemotherapy and radiation.  The prefix "cyto" denotes a cell.  (Source: MedicineNet.com)

H

Hematopoietic Cell Transplantation (HCT)

Bone marrow transplant is the most familiar form of HCT, involves taking stem cells from donor bone marrow and transplanting them into a patient whose bone marrow is compromised.  The transplanted stem cells can then develop into normal blood cells, and the patient essentially gains a new immune system.

HCT also comprises two newer methods: peripheral blood cell transplantation and cord blood transplantation. Peripheral blood and cord blood (from the umbilical cord) both yield stem cells, which can be transplanted just as bone marrow can.

Diseases treated with HCT include hematologic cancers such as acute and chronic leukemias, lymphomas, Hodgkin’s disease, as well as myelodysplastic syndromes and myeloproliferative disorders. HCT is also useful in treating other cancers such as breast cancer and ovarian cancer, as well as noncancerous conditions such as inherited disorders of the bone marrow and autoimmune diseases such as scleroderma.  (Source: City of Hope) 

I

Intestinal Trefoil Factor (ITF)

Intestinal Trefoil Factor is a naturally found protein found primarily on mucosal surfaces, including those in the mouth, esophagus and intestines.  ITF is also present in other tissues, including the eye and lung.  The protein, also known as TFF3, is known to promote mucosal restitution and repair.  (Source: The GI Company)

N

Neutropenia

Neutropenia is an abnormally low number of neutrophils in the blood.  Neutrophils serve as the major defense of the body against acute bacterial and certain fungal infections. Neutrophils usually constitute about 45 to 75% of all white blood cells in the bloodstream. When the neutrophil count falls below 1,000 cells per microliter of blood, the risk of infection increases somewhat; when it falls below 500 cells per microliter, the risk of infection increases greatly. Without the key defense provided by neutrophils, people have problems controlling infections and are at risk of dying from an infection. (Source: The Merck Manuals - Home Edition)

O

Oral Mucositis (OM)

Oral Mucositis is the principal oral side effect of chemotherapy, radiation, and chemoradiation. Altered mucosa can predispose patients to bacterial, fungal, and viral superinfection, and OM often results in physiological/functional impairment and psychological distress, producing a negative impact on quality of life.  (Source: ONCOLOGY Nurse Edition)

Currently available products are usually inadequate, and more effective treatment to minimize the extent and duration of mucositis is clearly needed. Historically, treatment of mucositis has been palliative and aimed at minimizing mucosal trauma. Treatments include frequent mouth cleansing and rinsing with buffered saline and fluoride solutions and administration of topical and systemic antimicrobial agents. Mucositis and infection of the mouth have remained major complications despite the usual oral care provided for patients with cancer.  (Source: Access Pharmaceuticals)

The terms oral mucositis and stomatitis are often used interchangeably at the clinical level, but they do not reflect identical processes. Oral mucositis describes inflammation of oral mucosa resulting from chemotherapeutic agents or ionizing radiation. Mucositis typically manifests as erythema or ulcerations. It may be exacerbated by local factors. Stomatitis refers to any inflammatory condition of oral tissue, including mucosa, dentition/periapices, and periodontium. Stomatitis thus includes infections of oral tissues, as well as mucositis as defined above.  (Source:  National Cancer Institute)

S

Squamous Cell Carcinoma

Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma.  (Source: National Cancer Institute)