Press Release Source: Pharming Group N.V. on Tuesday December 28, 2010, 8:13 am EST

LEIDEN, NETHERLANDS–(Marketwire – 12/28/10) – Biotech companyPharming Group NV (NYSE Euronext: PHARM) and specialty biopharmaceuticalcompanySantarus, inc (NASDAQ:SNTS – News) today announced the submission of aBiologicsLicense Application (BLA) to the US Food and Drug Administration (FDA) toobtainmarketing approval for Rhucin(®) (recombinant human C1inhibitor) for thetreatment of acute angioedema attacks in patients with HereditaryAngioedema(HAE).

The safety and efficacy of Rhucin for the treatment of HAE attackswereevaluated in two randomized placebo-controlled studies and are supported byfouropen label treatment studies. Both placebo-controlled clinical studiesshowedstatistically significant and clinically relevant improvement in theprimaryendpoint of time to beginning of relief of symptoms at Rhucin dosagestrengthsof 50 U/kg and 100 U/kg compared to placebo. In October 2010, PharmingreceivedMarketing Authorization for Ruconest(™ )(Rhucin in non-Europeancountries)for the treatment of acute HAE in the European Union. Pharming hasupdated theclinical dataset reviewed and approved by the European Medicines Agencywithadditional patient data and analyses. In total, the BLA dossier includesnineclinical studies covering 714 administrations in 190 subjects.

Santarus has licensed certain exclusive rights from Pharming tocommercializeRhucin in North America for the treatment of acute attacks of HAE andotherfuture indications. under the terms of the license agreement, a $5millionmilestone is payable to Pharming upon FDA acceptance for review of theBLA forRhucin.

About Rhucin (Ruconest in European countries) and Hereditary Angioedema

Rhucin (INN conestat alfa) is a recombinant version of the human protein C1inhibitor (C1INH). Rhucin is produced through Pharming’s proprietarytechnologyin milk of transgenic rabbits and in Europe is approved under the nameRuconestfor treatment of acute angioedema attacks in patients with HAE. The FDA hasgranted Orphan Drug and Fast Track Status to Rhucin for the treatment ofacuteattacks of HAE, a genetic disorder in which the patient is deficient in orlacksa functional plasma protein C1 inhibitor, resulting in unpredictable anddebilitating episodes of intense swelling of the extremities, face, trunk,genitals, abdomen and upper airway. The frequency and severity of HAEattacksvary and are most serious when they involve laryngeal edema, which canclose theupper airway and cause death by asphyxiation. According to the USHereditaryAngioedema Association, epidemiological estimates for HAE range from one in10,000 to one in 50,000 individuals. Based on prior discussions with theFDA,Pharming is planning to initiate an additional randomizedplacebo-controlled, clinical study with Rhucin in approximately 50 patientsto provide additionaldata in support of the 50 U/kg dose. Data from the placebo-controlledstudywill also be used to provide additional validation of the visual analogscaleused in measuring the clinical effects of Rhucin.

About Pharming Group NV

Pharming Group NV is developing innovative products for the treatment ofunmetmedical needs. Ruconest™ (Rhucin(®) in non-European territories) isarecombinant human C1 inhibitor approved for the treatment of angioedemaattacksin patients with HAE in all 27 EU countries plus Norway, Iceland andLiechtenstein. The product is also under development for follow-onindications,i.e. antibody-mediated rejection (AMR) and delayed graft function (DGF)following kidney transplantation. Pharming’s advanced technologies includeinnovative platforms for the production of protein therapeutics, technologyandprocesses for the purification and formulation of these products.Additionalinformation is available on the Pharming website, pharming.com.

Santarus, inc. is a specialty biopharmaceutical company focused onacquiring,developing and commercializing proprietary products that address the needsofpatients treated by physician specialists. The company’s currentcommercialefforts are focused on GLUMETZA(®) (metformin hydrochloride extendedreleasetablets) and CYCLOSET(®) (bromocriptine mesylate) tablets, which areindicatedas adjuncts to diet and exercise to improve glycemic control in adults withtype2 diabetes. CYCLOSET was commercially launched in November 2010.

Santarus also has a diverse development pipeline with three late-stageproductcandidates in Phase III clinical programs: ULTESA™ (budesonideMMX(®)) forinduction of remission of active ulcerative colitis, rifamycin SVMMX(®) fortreatment of travelers’ diarrhea and RHUCIN(®) (recombinant human C1inhibitor)for treatment of acute attacks of hereditary angioedema. In addition,Santarusplans to initiate a Phase I clinical study in the first half of 2011 withSAN-300, its anti-VLA-1 antibody, which the company expects toinvestigate for thetreatment of rheumatoid arthritis. more information about Santarus isavailableon the company’s website at santarus.com.

Pharming and Santarus caution you that statements included in this pressreleasethat are not a description of historical facts are forward-lookingstatements.These forward-looking statements include statements regarding thepotentialattributes of the RHUCIN (recombinant human C1 inhibitor) developmentproductand its potential to treat HAE or other indications. The inclusion offorward-looking statements should not be regarded as a representationby Pharming orSantarus that any of its plans or objectives will be achieved. Actualresultsmay differ materially from those set forth in this release due to therisks anduncertainties inherent in Pharming’s and Santarus’ businesses,including,without limitation: whether the FDA accepts the BLA submission andapprovesRHUCIN in a timely manner or at all; risks related to the timing andsuccess ofplanned development programs for RHUCIN, including the planned clinicalstudydesigned to provide additional data in support of the 50 U/kg dose;Santarus’ability to generate market demand and sales of RHUCIN, if approved;competitionfrom other products, unexpected adverse side effects or inadequatetherapeuticefficacy of RHUCIN; the ability to ensure continued supply of RHUCIN; thescopeand validity of patent protection or other regulatory exclusivity forRHUCIN;risks related to the license and supply arrangements betweenPharming andSantarus, including the potential for termination of the arrangements;otherdifficulties or delays in development, testing, manufacturing andmarketing of,and obtaining and maintaining regulatory approvals for, Pharming’s andSantarus’products; and other risks detailed in prior press releases as well as inpublicperiodic filings with the Securities and Exchange Commission.

You are cautioned not to place undue reliance on theseforward-looking statements, which speak only as of the date hereof.All forward-looking statements are qualified in their entirety by thiscautionary statement andneither Pharming nor Santarus undertakes any obligation to revise or updatethisnews release to reflect events or circumstances after the date hereof.Thiscaution is made under the safe harbor provisions of Section 21E of thePrivateSecurities Litigation Reform Act of 1995.

Santarus(®) and ULTESA(™) are trademarks of Santarus, inc.GLUMETZA(®) is aregistered trademark of Biovail Laboratories International S.r.l.licensedexclusively in the United States to Depomed, inc. CYCLOSET(®) is aregisteredtrademark of VeroScience LLC. MMX(®) is a registeredtrademark of CosmoTechnologies Limited. RHUCIN(®) and RUCONEST™ are trademarksof PharmingGroup NV.

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Source: Pharming Group N.V. via Thomson Reuters ONE

SAN JOSE, California, November 15, 2010 /PRNewswire/ —

– SI-BONE commences surgeon training at labs in Salzburg, Austria

SI-BONE, Inc. (San Jose, California), a medical device company that ispioneering the use of a minimally invasive surgical (MIS) device to treat thesacroiliac (SI) joint announced today that it has received a CE mark for itsiFuse Implant System(TM). a CE mark is the quality assurance certificationrequirement recognized by members of the European Union for sales into thosecountries. The company has also received ISO 13485 Certification, whichdemonstrates that it provides medical devices and related services thatconsistently meet customer and regulatory requirements.

The iFuse Implant system is a minimally invasive surgical (MIS) systemcomprised of titanium implants coated with a porous plasma spray that acts asan interference surface fit, which helps decrease implant motion. The iFusehas a substantial thickness and sophisticated metallurgy, which providesimmediate post-operative fixation, accomplishing the goal of traditional openSI joint fusion through an MIS approach. Clinical publications haveidentified the SI joint as a pain generator for up to 22% of low back painpatients and that up to 75% of post-lumbar fusion patients develop SI jointdegeneration within 5 years of surgery. These represent significant unmetclinical needs and, when conservative therapy fails, iFuse may provide an MISoption.

The first European surgeon training sessions were held in October andmost recently for November in Salzburg, Austria. These sessions are presentedby surgeon faculties who have performed dozens of iFuse surgeries in theUnited States. The company´s European Training and Product Manager, VanesFrison, is coordinating the labs.

Commenting on the CE Mark and EU launch, Jeff Dunn, President and CEO, said, “The iFuse Implant system provides spine surgeons with a uniqueminimally invasive surgical approach to SI joint fixation/fusion. The CE markwill allow our EU Team to develop a presence in selected EU markets toaddress the needs of physicians committed to treating patients with SI jointproblems. SI-BONE looks forward to entering these markets because we offerthe only technology which provides an MIS solution to treat these SI jointconditions.”

“Our product provides a technologically advanced alternative to theconventional open SI joint fusion as well as an option for patients who havefailed conservative therapy. The key to the iFuse procedure is the devicedesign and minimally invasive technique. we insert the implants across the SIjoint in a one hour procedure and it gives us the stability that we need, “said Mark Reiley, M.D., Chief Medical Officer and founder of SI-BONE.

The CE mark for this system follows the clearance the company received inNovember 2008 from the Food and Drug Administration (FDA) to market its iFuseImplant system. The iFuse is indicated for use in fracture fixation of largebones and large bone fragments of the pelvis for conditions includingsacroiliac joint disruptions and degenerative sacroiliitis.

In addition to training and engaging key spine surgeons in the EU, surgeons in the US presented their initial clinical data at NASS in Orlandoon October 7th. Additional retrospective data was also presented at severalsignificant meetings, including the American Academy of Physical Medicine andRehabilitation (AAPM&R) on November 5, the Society of Minimally InvasiveSpine Surgery (SMISS) on November 6 and World Congress of Low Back & PelvicPain in Los Angeles on November 12.

In response to increasing awareness of SI joint disruption anddysfunction as debilitating symptom generators, SI-BONE, Inc. developed aninnovative, patented, intramedullary implant to treat the SI joint. Thecompany is also embarking on a post-market multicenter study to determine itseffect over time on SI joint pathology and on symptoms associated with SIjoint problems.

The iFuse Implant system is a commercially available device in the US. Inthe EU it is intended for fixation of large bones and large bone fragments ofthe pelvis for conditions including sacroiliac joint disruptions anddegenerative sacroiliitis. The iFuse procedure uses a minimal incision fordelivery and implantation of small, titanium implants. The implants arecoated with a porous plasma spray that acts as an interference surface, designed to help decrease implant motion. These implants have substantialthickness and sophisticated metallurgy and are able to produce a muchstronger construct than that of conventional pins or screws used tosurgically fix boney structures. this implant technology from SI-BONE hasbeen previously used successfully in well over 1,000 cases of dysfunctionalfoot joints.

SI-BONE, Inc. (San Jose, California) is a leading spinal medical devicecompany dedicated to the development of tools and products for diagnosing andtreating patients with low back issues related to sacroiliac (SI) jointpathology. The company has developed, and is manufacturing and marketing, less invasive approaches using implants for the treatment of SI jointpathology. SI-BONE has an experienced management team with extensiveexperience in orthopedic and spine medical devices.

SI-BONE, Inc.

Pancreatic Cancer Symptoms, Diagnosis and Treatment The cancer of the pancreas or carcinoma is a pancreatic cancer tract. the tumors of neuroendocrine pancreas are another type of cancer, whose presentation is radically different. they are presented in the article neuroendocrine tumor.

Incidence and mortality of pancreatic cancer rate for 100 000 people

Impact

Mortality

CountryHFHFFinland13,09,912,8 Sweden9,8 Switzerland11,37,611,87,8 European Union9,76,510,77,3 France8,04,2 Luxembourg8,3 Portugal4,9It affects slightly more often men than women with incidence increasing with age (peak incidence at 75 years for men, 80 years for women). in older ages the rate is high e.g. 65 and above, the pancreatic cancer in Geneva about 5% and 6.5% respectively of male and female patients with cancer (at the front for men from lung cancer with 22.4% and for women the breast cancer with 19.8%). Pancreatic cancer is responsible for 2500 deaths per year in France.

Risk factors:

Contributing factors are a known pancreatitis chronic (post-alcoholic, tropical, or as part of a cystic fibrosis) or smoking. the obesity is another risk factor.

Familial forms exist four but genes involved remain unknown.

Symptoms

The development of cancer at the pancreatic head (60-70% of cases) creates a barrier biliary responsible for a rapid expansion of the gallbladder, a jaundice (for retention bladder) and pruritus (itching) caused by jaundice.

If cancer develops in the tail of the pancreas (7%), the clinical picture is dominated by transfixing epigastric pain (radiating to the loin), accompanied by a mass epigastric.

Other signs of cancer are sometimes significant alteration in general health (asthenia, anorexia, and weight loss), high occlusion by compression or invasion of the stomach or duodenum, a hepatomegaly irregular secondary to metastatic liver.

Finally, the destruction of the pancreas can cause pancreatic insufficiency (malabsorption and diarrhea) and endocrine (diabetes).

Diagnosis

The diagnosis rests on biopsy, pancreatic or liver metastases. this biopsy can be performed by trans-dermal, during a fiber optic gastro-duodenal, or during surgery.

An assay of CEA and CA 19-9 may refer to an adenocarcinoma; hormonal assays may characterize an endocrine tumor.

Imaging

The ultrasound is the gold standard to visualize the pancreas, an organ located deep in the abdomen and the observance of which is hampered by the interposition of bowel gas. this review remains frequent first-line exploration of abdominal pain. it allows, through this, to discover a significant number of tumors of the pancreas. its sensitivity is 75% lower than the scanner5. a normal ultrasound does not eliminate pancreatic cancer.

The scanner with abdominal injection of contrast medium iodine remains the gold standard. it allows also better assessing the local extent and existence of metastases, particularly in the liver and thereby determining the operability.

The MRI has a sensitivity intermediate between the scanner and ultrasound.

The endoscopy may insert a tube into the duodenum until the emergence of the pancreatic duct. Injection at this level of contrast with radiography allows a CHOLANGIOPANCREATOGRAPHY. this examination may detect a narrowing occasionally to one of the channels, which may reflect a compressive tumor. this review, however, a low-level performance diagnosis. By coupling the endoscope with an ultrasound probe, gives an ultrasonography. this review has a very good sensitivity for detecting tumors, even small sizes7. this examination also allows directed biopsy.

The goal is to visualize the pancreatic tumor, and seek lymph node metastases, liver, or peritoneal. we also study the relationship with the portal vein.

Pancreatic cancer can take many different forms: – in 90% of cases, reached the head of the pancreas – 10% of cancer cases correspond to the body or tail of the pancreas.

The CA 19.9 marker is the most interesting, primarily in assessing the effectiveness of treatment (rate collapses) and the detection of recurrence (rate rises again). it is, cons, little used in routine screening, its elevation is not specific for pancreatic cancer.

The pancreatic adenocarcinoma histology may have several forms:

There are cystic tumors of the pancreas that can degenerate (cystadenocarcinoma) or tumors of the excretory ducts of the pancreas (IPMT).

Differential Diagnosis

There are cancers of the endocrine pancreas (very rare twenty times less common than exocrine), revealed by their hormonal secretion, thus giving: insulinoma, glucanome, VIPomas … Tumors, often very small, are difficult to locate and resect. An ampulloma (tumor of the ampulla of Vater) can give symptoms similar to adenocarcinoma of the head, but it is a tumor of the bile ducts, much better prognosis. Similarly the lower bile duct cholangiocarcinoma may be confused with pancreatic cancer. the prognosis is very bleak.

Classifications

1.       TNM classification (UICC 2002)

2.       T (tumor)

3.       Tx Insufficient information to classify the primary tumor

4.       T0 No evidence of primary tumor

5.       Tis Carcinoma in situ

6.       T1 Tumor limited to pancreas <2 cm in greatest diameter

7.       T2 Tumor limited to pancreas,> 2 cm in greatest diameter

8.       T3 Tumour extends directly to any of the following organs: duodenum, bile duct, peripancreatic tissue.

9.       T4 Tumour extends directly to any of the following organs: stomach, spleen, colon, adjacent large vessels

N (Regional Lymph Nodes)

10.   Nx Insufficient information to classify the regional lymph nodes

11.   N0 No regional lymph node metastasis

12.   N1 Regional lymph node

13.   N1a invasion of a single node

14.   N1b Metastasis in multiple lymph

M (Distant metastasis)

15.   Mx Insufficient information to classify distant metastases

16.   M0 No distant metastasis

17.   M1 Presence of metastasis (s) remotely

Prognostic Factors

Pancreatic cancer is a tumor with very poor prognosis.

When the diagnosis of pancreatic cancer is increased, the chance of survival at 5 years is 1 to 4%. twenty percent of patients operated on are fully alive at 5 years. in contrast to patients unrespectable and metastatic median survival was 6 months and 5-year survival is zero.

Treatment

Given the poor prognosis, it is legitimate to consider aggressive treatment for patients in good general condition for which surgery is best possible. when the patient is inoperable (bad condition, lesion unrespectable metastases) the quality of life must be preserved as long as possible. Supportive cares were then predominant.

Therapeutic Approaches

Surgery

The surgery was the first-line treatment for a tumor not exceeding a certain size and with no metastasis or too intimate contact with the portal vein, but the location of this tumor because it is not easily accessible (many veins behind). moreover, recent protocols show an advantage to pursue a radio-chemotherapy pre-and postoperatively in selected cases. there section is possible only in 20% of cases. Loco regional relapse occurs, however, in 70 to 80% of cases. the surgical resection of the pancreatic head (cephalic duodeno-pancreatectomy) is heavy, due to venous reports, tracts, and bile. it may not be offered to a patient in good general condition, in the absence of respiratory or cardiac defect. for tumors of the tail of the pancreas, surgery is the reference spleno-pancreatic tail.

In the case where no curative surgery is possible, we prefer, if necessary, palliative surgery to treat the symptoms, allowing the flow of bile and food bowl:

Double bilio-digestive. These diversions are more often performed endo-scopically, with placement of stents and duodenal bile.

Radiotherapy or Chemo Radiotherapy

In cases of advanced tumor, the radio-chemotherapy is used either after surgery or in lieu thereof. Radiation therapy delivers 45-50 Gy in 5-6 weeks and is associated with 5-FU continuous low dose. Used after surgery, experiencing “adjuvant” radio chemotherapy allows a reduction in local recurrence but the gain in survival remains low. this strategy is controversial at present.

Chemotherapy

The chemotherapy is used mainly in the metastatic setting, in addition to symptomatic treatment (bypass surgery, nutrition, analgesics, psychological support). the products are mainly used gemcitabine9, and to a lesser extent, 5-FU, cisplatin andoxaliplatin.

In metastatic disease, the palliative effect is demonstrated for the combination of gemcitabine and 5-FU and cisplatin. in the adjuvant setting, that is to say after curative surgery, chemotherapy reduces the risk of recurrence or delaying it.

The chemotherapy protocols validated in pancreatic cancer are:

Gemcitabine

Cisplatin – sLV5FU2

GEMCEA

GemOx

Therapeutic strategies presented here are based on the repository of the French Federation of Digestive Oncology, 2005. Modes of treatment may vary from one country to another and from one region to another.

Resectable tumor

The small tumors in patients are able to withstand a surgical resection with curative intent. the standard treatment is surgery with curative type duodeno-cephalic pancreatectomy for tumors of the pancreas head and caudal spleno-pancreatectomy for tumors of the pancreatic tail. Adjuvant treatment depends on the quality of resection.

In case of complete resection with adequate margins (R0 resection), adjuvant chemotherapy include LV5FU2 for 6 months.

If microscopic incomplete resection (R1) or macroscopic (R2) will include either the adjuvant chemotherapy of 5FU-cisplatin type or gemcitabine for six months or a radio-chemotherapy.

Unresectable Tumor

If the tumor is not resectable at the outset but it is likely that treatment with radiotherapy or chemotherapy will reduce the tumor enough to make it operable, it is possible to begin treatment, said “neo-adjuvant ‘by a combination radio-chemotherapy (cisplatin with 5FU) and then reassess the operability of the lesion. in one third of cases, curative surgery may be prolonged, leading to a more prolonged survival10. If the lesion is permanently inoperable, there is a choice between chemotherapy alone, a combination radio-chemotherapy and chemotherapy followed by an association of radio-chemotherapy for patients whose tumors decreased under chemotherapy.

Metastatic tumor

1st line: 5FU-cisplatin or gencitabine 2e online: gencitabine, or 5FU-cisplatin GemOx according to the first line.

Author: Peter Norman

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