Biohit Oyj has been granted a methods patent related to GastroPanel in China

Biohit Oyj, stock exchange release, 25.9.2012, EET 18:00

Biohit Oyj was recently granted a patent protecting the GastroPanel invention in China. The patent will protect “the method for diagnosing atrophic gastritis” and is in effect until 3 January 2022. Patents relating to the GastroPanel invention have also been applied and granted in Europe, Japan and the United States.

GastroPanel is a unique examination that is carried out as a blood sample test based on biomarker tests. It has been designed for the early diagnosis and screening of possible Helicobacter pylori infections or atrophic gastritis in patients suffering from stomach discomfort as well as asymptomatic people (www.gastropanel.fi). Over half of the world’s population suffers from Helicobacter pylori infections, and it has been estimated that approximately 500 million people have atrophic gastritis. In China, approximately two in three of the entire population suffer from a Helicobacter pylori infection.

Helicobacter pylori infection and atrophic gastritis can lead to gastric cancer, which is one of the most fatal cancers in China. It is possible to significantly improve the prognosis of Helicobacter pylori infections and atrophic gastritis as well as the early stages of cancer advancing from those diseases with early diagnosis that enables treatment of the diseases. CanAg Diagnostic (Beijing), a Chinese affiliate of the Japanese company, Fujirebio, has started the marketing and sales of GastroPanel tests in China. CanAg Diagnostics has approximately 200 retailers in China.

Anacidic stomach caused by atrophic gastritis is the most well-known risk factor of gastric and oesophageal cancer. In addition, an anacidic stomach can lead to malabsorption of vitamin B12, iron, magnesium, calcium and certain drugs. The risk of gastric and oesophageal cancer caused by an anacidic stomach can be decreased with unique Acetium capsules that have been developed by Biohit Oyj. The capsules efficiently bind (neutralise) carcinogenic acetaldehyde formed in an anacidic stomach (see Additional information).
 

 Biohit Oyj

Semi Korpela, CEO and President

Tel. +358 9 773 86 333
semi.korpela@biohit.fi

Additional Information

Diseases of the gastrointestinal tract are a major cause of high healthcare costs globally, and the costs are growing uncontrollably. Due to late diagnosis, the treatment practices of many cancers – particularly cancers of the gastrointestinal tract – are inadequate. Many patients either do not receive safe, effective treatment or are dissatisfied with the treatment they get. The ageing of the population is leading to an increase in gastrointestinal cancers as well as vitamin B12 and calcium deficiency resulting from an achlorhydric stomach. In addition, more diseases are caused by these deficiencies. This puts a rapidly growing burden on well-being and national health and reduces people’s ability to remain in longer-term employment.

In Finland, approximately 940 people are diagnosed with oesophageal and stomach cancer every year, and 730 people die from these diseases. At an early and curable stage, these cancers are often asymptomatic or involve minor symptoms. That is why these cancers are too often treated for too long with self-medication, such as the widely advertised medications decreasing gastric acid secretion or different dietary supplements. Patients are therefore left without diagnosis and thus do not receive treatment. The prognosis of these cancers is especially poor due to late diagnosis. It is possible to significantly improve the prognosis of atrophic gastritis as well as the early stages of cancer as a result with early diagnosis thereby enabling treatment of the disease.

GastroPanel reliably detects H. pylori infection, as well as atrophy of the gastric mucosa and dysfunction of the stomach (atrophic gastritis) that are caused by H. pylori infection or by an autoimmune disease, which, in turn, leads to achlorhydric stomach. Mouth bacteria and yeasts are transmitted via swallowing saliva, and they can persist and produce carcinogenic acetaldehyde from the sugars found in food and alcohol in the achlorhydric stomach.

The 13C urea breath test, stool antigen tests and antibody tests extensively used to diagnose various abdominal complaints (dyspepsia) do not detect atrophic gastritis (achlorhydric stomach), which is the major risk factor for gastric and oesophageal cancer.

 Based on the results of the Finnish Setti study, it has been estimated that the treatment and prognosis of stomach cancer among patients aged over 45 could be significantly improved in Finland by using the GastroPanel test as the primary examination for patients with abdominal complaints, and for screening and regular checkups for anyone aged over 45. This would allow the referral of at-risk patients for gastroscopy examinations in time to enable cancers to be detected at an early stage.  Regular checkups offer a wealth of reliable and valuable information that may be relevant for the patient's future health and quality of life.

If the patient has developed severe atrophic gastritis, the condition is typically permanent, and the patient will require follow-up tests due to the risk of cancer. These patients can reduce their risk of developing gastric and oesophageal cancer by taking Acetium capsules.

Measures to reduce the risk of gastric and oesophageal cancer include the GastroPanel test and the use of Acetium capsules which, when taken in connection with food and alcohol intake, effectively bind (neutralise) carcinogenic acetaldehyde in the stomach.

Acetium capsules, which are available in pharmacies without prescription, are recommended to those with

1. an achlorhydric or low-acid stomach caused by atrophic gastritis resulting from Helicobacter pylori infection or an autoimmune disease, which can be diagnosed with GastroPanel (500 million worldwide),

2. an untreated chronic Helicobacter pylori infection, which can be reliably diagnosed with GastroPanel (more than 500 million people worldwide),

3. the long-term need to use medications that reduce gastric acid (HCl) secretion (PPI medication and H2 blockers); approximately 5-10% of Western population use these occasionally or regularly, and possibly more than 500,000 people in Finland,

4. people who have undergone stomach surgery (over a million people worldwide),

5. people with the gene mutation that affects acetaldehyde metabolism: 30–50% of Asians show ALDH2 deficiency.

Although data on the effectiveness of Acetium in the prevention of gastric and oesophageal cancer is not yet available, there is conclusive scientific evidence to suggest that acetaldehyde, a group I carcinogen, causes cancer, and that acetaldehyde is generated in an achlorhydric stomach, which is a known risk factor for gastric and oesophageal cancer.  Exposure to acetaldehyde is linked to more than three million new gastrointestinal cancers per year globally, which represents approximately 25 per cent of all cancers (visit www.acetium.com to test your exposure to acetaldehyde).

Acetium has been granted a wide patent protection in Europe. Patents are also pending outside Europe (www.biohithealthcare.com: Investors/ Stock Exchange Releases: 20/07/2012: European Patent Awarded to Biohit Oyj’s Acetium).

IARC, the WHO’s agency on cancer research, declared in October 2009 that the acetaldehyde in alcoholic beverages and naturally generated in alcohol is a group 1 carcinogen and therefore as carcinogenic as asbestos, formaldehyde and benzene.

International research groups recommend blood sample biomarker tests for the diagnosis and screening of gastric diseases (Investors/ Stock Exchange Releases: 08/06/2012).

Unlike the Helicobacter pylori examinations still being used (13C urea breath test and stool antigen test), the GastroPanel biomarker test reliably detects H. pylori infection, the typically asymptomatic condition atrophic gastritis, and associated risks, including cancer.

As much as 20-40% of the Western population suffers from dyspepsia, which, according to conventional medical practice, requires gastroscopy. There are no resources available, nor is there any need for such examinations or high-risk experimental medications. The GastroPanel biomarker test allows only ill and at-risk patients to be referred for gastroscopy and treatment. This increases patient safety, and saves 40-70% of scarce and expensive endoscopy capacity to be used for colonoscopies for early diagnosis and prevention of colorectal cancer. Particularly with elderly people, problems in the colon are often the cause of dyspepsia complaints. It is therefore advisable to supplement GastroPanel with a ColonView test to select at-risk patients for colonoscopy (www.biohithealthcare.com: Diagnostics / Product brochures).

The April 2012 Maastricht IV consensus report of the European Helicobacter Pylori Study Group recommends blood sample biomarker tests as a reliable method of diagnosis of diseases of the stomach mucosa and associated risk conditions. Researchers recommend biomarker tests for the diagnosis and follow-up of Helicobacter pylori infection and especially for atrophic gastritis that causes achlorhydric stomachs, in addition to recommending the screening of asymptomatic patients.

The international Healthy Stomach Initiative group’s 16 gastroenterology experts from 12 countries (www.hsinitiative.org) came to the same conclusions. Biomarker tests can be used to diagnose and screen atrophic gastritis and related risks in both asymptomatic patients and patients with abdominal discomfort (www.biohithealthcare.com: Investors/ Stock Exchange Releases: 17/02/2012 Biohit Oyj’s GastroPanel biomarker test recommended).

The state-of-the-art, highly informative, safe and cost-effective GastroPanel biomarker test for diagnosing dyspepsia (various upper abdominal complaints) and Helicobacter pylori infection does not involve any of the problems described below.

•The 13C urea breath test (UBT), stool antigen test and antibody tests alone do not detect atrophic gastritis of the corpus caused by H. pylori infection or autoimmune disease, or atrophic gastritis of the antrum caused by H. pylori infection. Atrophic gastritis is almost always asymptomatic and usually incurable.

• Undiagnosed atrophic gastritis of the corpus (achlorhydric stomach) may cause gastric and oesophageal cancer and malabsorption of vitamin B12, iron, magnesium, calcium and certain drugs.

• Calcium deficiency causes osteoporosis. Vitamin B12 deficiency can cause pernicious anaemia, dementia, depression and damage to the peripheral nervous system.

• The absorption of several drugs such as dipyridamole, some iron products and antifungals (fluconazole, itraconazole), thyroxine and atazanavir is considerably impaired in an achlorhydric stomach. Particularly in senior citizens, the risk of severe intestinal infections (such as giardiasis, malaria, Clostridium difficile and E. coli EHEC) increases.

• Atrophic gastritis in the gastric antrum increases the risk of peptic ulcer disease and gastric cancer. If both the antrum and corpus mucosa are atrophic, this condition poses the highest risk for gastric cancer known to date. In some cases, gastric cancer is directly caused by H. pylori and gastritis. Less than 1% of the population has hereditary gastric cancer.

• Furthermore, none of the aforementioned three H. pylori tests provide any information on excessive gastric acid secretion, which in patients with gastro-oesophageal reflux disease may cause complications from this disease. Such complications are often asymptomatic and include ulcerative oesophagitis and Barrett’s oesophagus, which may lead to oesophageal cancer if left untreated. If complications of the gastroesophageal reflux disease are suspected due to excessive acid secretion, or if the patient has atrophic gastritis or symptomatic Helicobacter pylori infection, gastroscopy is required to rule out cancer and other risks.

• In addition, the 13C urea breath test and stool antigen test may give up to 40% false negative results: in other words, the infection including cancer and other risks may be left undiagnosed if the patient has atrophic gastritis, MALT lymphoma or bleeding peptic ulcer disease, or if the patient is currently receiving antibiotics or PPI treatment.

In order to prevent medical malpractice, unnecessary costs and even unnecessary deaths caused by cancer, the current Helicobacter pylori tests should be replaced by the GastroPanel biomarker examination. With the GastroPanel tests readily available, treating patients suffering from stomach discomfort without further diagnosis can no longer be justified. Risky self-treatment of stomach discomforts may delay the diagnosis of, for example, precancerous gastric lesions until the disease has progressed beyond treatment. Approximately one-third of the population in Finland suffer from stomach discomfort. Tens of thousands of patients from this group receive proton pump inhibitor (PPI) treatment or take prescription-free PPI medication, regardless of the fact that they already have an achlorhydric stomach caused by atrophic gastritis and the associated risks of cancer and other diseases.

Proton pump inhibitor (PPI) medications, both prescribed and those available without prescription, come with the following warning: ”If the patient has alarming symptoms (e.g. significant unintentional weight loss, persistent continuous vomiting, difficulty swallowing, blood in vomit or in stool) and a suspected or diagnosed peptic ulcer, any malignant conditions must be ruled out because PPI treatment can alleviate the symptoms and delay diagnosis.” This warning is justified but insufficient to lower the extremely high mortality rate in patients with stomach and oesophageal cancer. When “alarming symptoms” have appeared, the cancer has usually advanced to a non-curable stage. Despite this warning and without ruling out atrophic gastritis (achlorhydric stomach), stomach discomfort is very often treated with PPI and other medications that reduce gastric acid (HCl). Furthermore, atrophic gastritis and the associated cancer risk caused by both a Helicobacter pylori infection and an autoimmune disease typically cause few or no symptoms.

Osteoporosis and vitamin B12 deficiency represent a major public health problem among the elderly, and may typically be caused by asymptomatic undiagnosed atrophic gastritis. A person with an autoimmune atrophic gastritis of the corpus may simultaneously suffer from an another autoimmune disease, such as thyroiditis, celiac disease, rheumatoid arthritis and type 1 diabetes; or vice versa, a person with thyroiditis and type 1 diabetes often suffers from autoimmune asymptomatic atrophic gastritis and the resulting risk of gastric and oesophageal cancer as well as vitamin B12 deficiency. GastroPanel helps to detect at-risk patients in time and refer them to gastroscopy and treatment.

Literature on GastroPanel

1.Malfertheiner et al. Management of Helicobacter pylori infection. The Maastricht IV/ Florence Consensus Report. gut-bmj.com on May 18, 2012. European Helicobacter Pylori Study Group, ESPSG
2.Agreus et al. Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers, Scandinavian Journal of Gastroenterology 2012; 47: 136 – 147)
3.WHO. http://www.iarc.fr/en/media-centre/pr/2009/pdfs/pr196_E.pdf

Literature on Acetium and acetaldehyde

1. Salaspuro V, Hietala J, Kaihovaara P, Pihlajarinne H, Marvola M, Salaspuro M. Removal of acetaldehyde from saliva by a slow-release buccal tablet of L-cysteine. Int J Cancer 2002; 97:361-4.

3. Salaspuro VJ, Hietala JM, Marvola ML, Salaspuro MP. Eliminating carcinogenic acetaldehyde by cysteine from saliva during smoking. Cancer Epid Biomark Prev 2006; 15:146-9.

4. Kartal A, Hietala J, Laakso I, Kaihovaara P, Salaspuro V, Sakkinen M, et al. Formulation and in vivo evaluation of L-cysteine chewing gums for binding carcinogenic acetaldehyde in the saliva during smoking. J Pharm Pharmacol. 2007;59:1353-8.

5. Linderborg K, Marvola T, Marvola M, Salaspuro M, Färkkilä M, Väkeväinen S. Reducing carcinogenic acetaldehyde exposure in the achlorhydric stomach with cysteine. Alcoholicm Clin Exp Res, 2011;35:1-7.

Biohit is headquartered in Helsinki and its subsidiary is located in the UK. Since 1999, Biohit’s Series B shares (BIOBV) have been listed in the NASDAQ OMX Helsinki Oy Small cap/Healthcare sector (http://www.biohithealthcare.com/investors).