This newsletter will cover arthritis and pain management for pharma/biotech and market data and trends in pulmonology and gastroenterology for medical device. To read last month's topics on diabetes, COPD, orthopedic or general surgery, please click on the newsletter archive link.

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There is no cure for Osteoarthritis (OA). Drugs are not recommended for pain management of OA, but surgery maybe inevitable as we age. This is one of the reasons why orthopedic devices, knee and hip replacement are growing (see July newsletter for orthopedic devices). Nutriceuticals have grown rapidly as an alternative to pain medications for the same reason.

There is no cure or drug to halt the progression of Rheumatoid Arthritis (RA). There is still a need for new classes of medications. All classes of medications currently used for RA have either side effects; compliance issues (injectables/IV drugs); and efficacy issues, since no one drug works universally and as RA progresses, drugs may cease to relieve symptoms.  This is the reason many pharma and biotech companies have focused on this area. 

For more information on the trials listed below, feel free to contact us.

Background and Market Data

The two most common types of arthritis are:

1) Osteoarthritis (OA) - primarily involves the weight-bearing joints: knees, hips, cervical and lumbosacral spine, and feet. Many factors contribute to OA: aging that causes normal wear and tear; obesity that addsstress tothe joints; injury; muscle weakness; and heredity. Not everyone gets OA as they age and its cause is unknown. There is no cure for the disease.

There are five treatment approaches to OA: 1) exercise, 2) weight control, 3) rest to relieve joint stress 4) non-drug pain medications or alternative therapies, and 5) surgery.

Nutritional supplements such as glucosamine and chondroitin sulfate have been reported to improve the symptoms of OA, including vitamins D, C, or E, or beta carotene.

2) Rheumatoid Arthritis (RA)  - is an autoimmune disease. The immune system attacks and first causes inflammation in the synovium, the membrane that surrounds a joint and creates a protective sac, then progresses to the cartilage and then eventually bone. RA usually affects the joints symmetrically and causes a lot of pain.

The treatment approach for RA is medication that is both inexpensive and produces few side effects, to reduce inflammation and pain. In addition, lifestyle modification is recommended to preserve joint motility and prevent further damage.

There is an extensive list of medications to treat RA. For a complete list, click here.

1. Non-steroidal Anti-inflammatory Drugs (NSAIDs) reduce inflammation and pain.
2. Cox-2 Inhibitor, a new type of NSAID
3. Corticoid steroids reduce inflammation.
4. Biologics - Anti-TNFs block the action of a chemical called tumor necrosis factor (TNF) that is thought to play an important role in driving inflammation and tissue damage in certain kinds of inflammatory arthritis.
   1. All injectable drugs
5. Disease-modifying anti-rheumatic drugs (DMARDs) slow the disease's progress and reduce the amount of jointdamage.
6. Newer biologics - to be used if you do not have an adequate response to an anti-TNF drug
7. Combination products

In a National Health Interview Survey (NHIS) conducted from 2007-2009, an estimated 22.2% (49.9 million) of U.S. adults reported doctor-diagnosed arthritis or other rheumatic condition (27 million OA) and it is projected that 67 million people will have the disease by 2030. The prevalence of arthritis increased significantly with age and more women (24.3%) than men (18.2%) have arthritis. The survey also found that an estimated 9.4% (21.1 million) of U.S. adults reported arthritis-attributable activity limitation (AAAL) and 25 million people by 2030.

The latest statistics on RA rheumatoid arthritis is 1.3 million people in a 2005 U.S. Census data. The cost to treat arthritis and other rheumatic condition is $128 billion annually.

Trials

1. Regeneron and Sanofi have shown that their experimental antibody drug sarilumab, in combination with a standard RA treatment, methotrexate, has significantly improved symptoms of rheumatoid arthritis in RA patients compared to those patients treated with methotrexate alone in their Phase IIb "MOBILITY" trial.

2. Lexicon Pharmaceuticals' experimental arthritis drug, LX2931 did not fair well as there was an unusually high placebo response in a mid-stage study with doses of 70 mg or 110 mg. "Further study of LX2931 may well involve higher doses of the drug given the relatively benign safety profile observed to date..." said JP Morgan analyst Cory Kasimov.

3. German biotech 4SC's experimental pill vidofludimus, missed its primary goal in a mid-stage study as an alternatives to injected drugs. 4SC CEO Ulrich Dauer hoped that results of its mid-stage study would provide data and help land a partnership with a pharma company.

Osteoarthritis Trial

1. Tarsa Therapeutics has developed an oral recombinant salmon calcitonin for postmenopausal osteoporosis and received positive Phase III data, with expectation to file with the FDA later this year. Tarsa currently has calcitonin in a nasal and injectable form but due to compliance issues, developed this oral form.

Pain is difficult to treat because it's subjective and different for everyone particularly if there is no underlying disease. Our healthcare system and society is not accustomed to dealing with the unknown and some can be very judgmental. People are often ignored or dismissed especially when previous pain treatments have not worked.  

There were a lot of misconceptions of Fibromyalgia being a psychological problem and not a medical problem. Now researcher have shown that "the brain and spinal cord process pain signals differently; they react more strongly to touch and pressure, with a heightened sensitivity to pain. It is a real physiological and neurochemical problem."  Chronic Fatigue Syndrome which many times coincides with Fibromyalgia is another misunderstood disease.  It wasn't until the CDC defined Chronic Fatigue as a disease and advocated funding for research has the public started to become aware of this disease.  

Pain is treated like a symptom as oppose to a disease which is why there has not been a lot of advances in medicine for pain besides opioids and NSAIDs. More basic research is needed in finding the many mechanisms of pain as in the example above. In addition, the whole healthcare system has to change how it views and treat pain as summarized below from the study by the Institute of Medicine.

For more information on the trials listed below, feel free to contact us.

Background and Market Data

Everyone has experienced pain, but pain is unique to each individual. Pain, acute or chronic, is the most frequent reason for going to the doctor, taking pain medication and claiming work disability. Severe chronic pain affects us both physically and mentally in terms of quality of life and productivity. There are 116 million people with chronic pain and the annual economic cost of chronic pain in adults is $560-630 billion annually, including health care expenses (($261-300 billion) and lost productivity ($11.6-12.7 billion), according to an Institute of Medicine (IOM) new study.

Everyone is at risk for chronic pain. Chronic pain can result from a number of things: 1) age, such as arthritis, 2) genetic disposition, such as migraines, 3) chronic disease, such as cancer, 4) surgery due to severed nerve endings and 5) injury, such as low back pain.

A number of factors may contribute to why pain is aunique and subjective experience for each individual:  

1. genetic characteristics,
2. general health status and comorbidities,
3. pain experiences from childhood on,
4. the brain's processing system,
5. the emotional and cognitive context in which pain occurs,
6. and cultural and social factors

The IOM discovered that when pain was found to be caused by an underlying disease such as cancer, itwas accepted as real and treated with concern. Validation of the disease made the pain socially acceptable, and not trivializedby the health care system, families or communities. However, when the pain was not linked to an underlying disease, the cultural perception and response to pain was dramatically different. "Reactions ranged from care and compassion to judgmental opinions that lacked compassion and sometimes devolved into blaming or personalization of responsibility. The lack of a defined disease made the symptoms of pain and suffering less acceptable and more ascribed to overreaction, emotional instability, or worse. Because the pain could not be seen or measured "objectively" or interpreted within the context of the known, it was more likely to be dismissed, diminished, or avoided. The irony is that this pain and suffering, just like that of the patient with a known disease, could be life dominant-a disease in its own right."

The IOM's study conclusion was "Pain affects the lives of more than a hundred million Americans, making its control of enormous value to individuals and society. To reduce the impact of pain and the resultant suffering will require a transformation in how pain is perceived and judged both by people with pain and by the health care providers who help care for them. The overarching goal of this transformation should be gaining a better understanding of pain of all types and improving efforts to prevent, assess, and treat pain."

The committee's recommendations and the findings that support them fall into four areas: 1) pain as a public health challenge, 2) care of people with pain, 3) education challenges, and 4) research challenges. Two areas 1) care of people with pain and 2) research challenges will be covered here.

Care of People with Pain - an enormous number of Americans receive inadequate pain prevention, assessment, and treatment. This is due to the healthcare system lack of a valid and objective pain assessment criterion, lack of a training program for the healthcare professional on how to perform a supportive role in pain management, and lack of adequate reimbursement to support this role.

The IOM recommends that pain care needs to be tailored to each individual and that an interdisciplinary approach between the patient, PCP, specialty care, pain centers and the entire health care system. Financing, referral, records management, and other systems are needed to support this individualized care.

In addition, physicians need to provide patients with a realistic expectation for living with and managingchronic pain. Unfortunately, patients are often not informed or understand that identifying the best combination of treatments for themmay be a long process, filled with uncertainty in the treatment regiment.

Research Challenges - There have been great progress in the past several decades in the understanding of pain processes, its assessment and to some extent, the treatment of pain, but we have yet to scratch the surface. There is still a need for more basic research, biomarkers and biosignatures and psychosocial research.

The IOM recognizes that there are challenges for the medical industry in developing new drugs for pain:

The Difficulty of Developing New Analgesics - only a few drugs out of approximately 100 drugs that were approved by the FDA from 2005- 2009 were for chronic pain conditions such as arthritis or fibromyalgia. Other than the recent introduction of the "capsaicin patch for postherapeutic neuralgia, no new therapeutic agents have been approved that represent truly novel approaches to pain management and many pharma companies are leaving the pain market despite the growing need for more diverse pain products and an increasing population of people with serious pain conditions." Currently there are only two classes of drugs to treat pain: 1) opioids and 2) NSAIDs.

In order to development better medications for chronic pain, one has to look at pain as a disease of the central nervous system, which changes the treatment approach from a mechanism-based therapeutic approach rather than a symptom-based approach. When this is done, this will lead to more personalized medicine. However, in order to incentivize pharma companies to develop a pain medication that would only works on a small number of patients, the regulatory clinical trial process has to change. "To make new pain treatments available expeditiously will require improved pain models, measurement tools (including patient-reported assessments), and clinical trial designs."

The FDA has launched a Regulatory Science Initiative that includes a revised evaluation and accelerated approval processes to give people access to innovative products when they need them. One of the reasons the FDA created this initiative is the need for pain medications other than opioids that have less potential for abuse. A personalized drug that works for one person and not the other deters others from abusing a drug.

Trials

1) The FDA has once again rejected Pfizer and Pain Therapeutics' application for Remoxy, an extended-release version of oxycodone that has been altered to taste bad and be harder to chew properties the companies had hoped would make the drug less prone to abuse.

2) Endo Pharmaceuticals midstage results for its experimental chronic lower back pain drug Axomadol showed the new drug candidate did not meet the predetermined study end points for proving its effectiveness.

3) Carbylan BioSurgery announced positive results in its double-blind, multi-center clinical trial which evaluated the safety and effectiveness of Hydros-TA Joint Therapy and Hydros as compared to Synvisc-One in patients with osteoarthritis of the knee.    

4) Johnson & Johnson and AstraZeneca Plc stopped studies of the experimental painkiller fulranumab over concerns that a class of drugs once expected to generate as much as $11 billion in annual sales may raise the risk of joint damage.

5) Regeneron Pharmaceuticals Inc. of Tarrytown, New York, said the FDA had halted trials of its treatment in the class known as anti-nerve growth factors.

6) Pfizer Inc., the world's largest drugmaker, suspended trials of the pain drug tanezumab in June after reports that patients in one of its studies needed joint replacements. The move left nerve-growth inhibitors "a tainted class."

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Interventional Pulmonology is a relatively new market as the pulmonologist; a diagnostician becomes a therapeutic interventionalist similar to an interventional cardiologist. When the cardiologist became an interventionalist, great technology and advancement was development for early diagnosis and better treatment of diseases. The field of Interventional Pulmonology is following the same path for lung disease. New minimally invasive procedures and new devices described below have been developed for diagnosing and treatment of lung diseases. Analysts predict that the growth of the interventional pulmonary devices market will mirror the interventional cardiology devices market.

Background and Market Data

The pulmonary device market is segmented into three areas: 1) Pulmonary Drug Delivery Technologies, the dominate segment, 2) Respiratory Devices and 3) Interventional Pulmonary devices.

1) The global pulmonary drug delivery technologies market is projected to be $37.7 billion by 2015, according to Global Industry Analysts (GIA). This is due to the increasing incidence of respiratory disorders, asthma and COPD (see July newsletter for COPD) 

Pulmonary drug delivery technologies refer to a device and formulation of a drug for infusion into the body by thepulmonary (inhalation) route. These include metered dose inhalers (MDI), dry powder inhalers (DPI) and neubulizers. In 2007, the MDI market was $10.5 billion and the neubulizers market was $1.2 billion according to GIA. 

Advancements in formulating technology in dry powder inhalers are expected to replace MDIs. Advances include sophisticated device architectures, growing research activity in powder formulations, and innovations in particle engineering. The global market for DPIs is expected to surge at double-digits between 2007 through 2015.

The next generation of devices is systemic inhalable for all types of drugs. Supraer™ is a new aerosol delivery platform for high dose rate delivery of macromolecules and biologics. This delivery system claims to have the following advantages over DPI:

• Target drug directly to the diseased lung
• Reduce total administered dose compared to oral or IV
• Result in an improved therapeutic outcome

2) The global respiratory devices market is forecast to grow from $4.5 billion in 2010 to $7.1 billion by 2017 with a CAGR of 7%. The market is forecast to grow in response to the increasing incidence of respiratory diseases such as asthma, obstructive sleep apnea (OSA) and Chronic Obstructive Pulmonary Disease (COPD).

The Positive Airway Pressure (PAP) device market for obstructive sleep apnea is the largest segment and accounted for almost 58% of the total revenue generated in 2010 for global respiratory devices.  The PAP (includes CPAP, BiPAP, APAP) device segment will continue to have high growth and will remain the largest market segment. The global market for PAP is forecast to grow from $2.6 billion in 2010 to about $4.4 billion by 2017, with a CAGR of 8%. Reimbursement for PAP devices is helping to drive the market.

3) Interventional pulmonology is the treatment of breathing-related disorders such as asthma, lung cancer, COPD, and emphysema. The development of interventional pulmonology is changing the role of the pulmonologist from diagnostician to therapeutic interventionalist, similar to the interventional cardiologist.

The Interventional Pulmonary Market is predicted to mirror the growth of the Interventional Cardiology Market as new technologies drive US pulmonary sales to $3.8 billion in 2011, according to Health Research International.

For the interventional pulmonologist this may also entail theassessment of radiographic abnormalities such as pulmonary nodules, patients with pleural effusion, mediastinal adenopathy (avoiding surgical mediastinoscopy in many instances), and cough. It also requires interdisciplinary coordination with Thoracic surgeons for bronchoscopic procedures and artificial lungs.

Trends in Interventional Pulmonology:

1. Bronchial thermoplasty is a minimally invasive procedure that reduces excessive airway smooth muscle, decreasing the airways' ability to constrict and narrow during an asthma attack.
   1. The Alair® Bronchial Thermoplasty System delivers thermal energy to the airway wall in a precisely controlled manner in order to reduce excessive airway smooth muscle.
2. Endobronchial ultrasound (EBUS) is a relatively new procedure used in the diagnosis of lung cancer, lung infections, and other diseases that cause enlarged lymph nodes or masses in the chest. 
   1. The EBUS procedure allows physicians to perform a transbronchial needle aspiration (TBNA) to obtain tissue samples from the lungs and surrounding lymph nodes without conventional surgery.
   2. The samples can be used for diagnosing and staging lung cancer, detecting infections, and identifying inflammatory diseases that affect the lungs, such as sarcoidosis.
   3. The physician can perform a needle biopsy on lymph nodes using a bronchoscope inserted through the mouth. No incision is made compared to a mediastinoscope.

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The GI endoscopy market will continue to grow as technology become more sophisticated and even less invasive for diagnostic procedures. Capsule endoscopy is the fastest growing segment for this reason. It eliminates the pain and discomfort of a traditional endoscope for colonoscopies. Japanese researcher have recently developed a self propelled capsule that can be remotely controlled from the esophagus to the colon (See New Technology below).   

Virtual colonoscopy is an attractive diagnostic method except few insurance companies will reimburse for it.   There are a number of advantages of using virtual colonoscopy for the patient's comfort and safety, but it does not detect pre-cancerous polyps smaller than 10 millimeters. As technology advances for virtual colonoscopy, this will be widely available as another option.  

Flexible and rigid endoscopes will still be needed for treatment in removing polyps and biopsy. Advance technology has been developed to visualize not only the surface of the digestive track but several layers below in eliminating all suspected cancer or precancerous tissue.

Background and Market Data

The global market for GI endoscopy devices is predicted to exceed $6.5 billion by 2016, with a compounded annual growth rate of 4 % spanning from 2009 to 2016, according to GBI research.

The US is the largest market for endoscopy devices, contributing 46 % to the market followed by Europe with 27%.  Currently, the value of the U.S. market for endoscopy devices is $2.3 billion and is forecast to reach $3.1 billion by 2016, increasing the U.S. market to 48%.

Aging populations and rising obesity rates are the main factors for GERD and cancers in the US.

More than 14 million colonoscopies are performed annually in the US and colon cancer is still the second largest type of cancer. Stomach and esophageal cancers are higher in Asia but as Asian countries become more westernized, this will lead to higher rates of non-malignant diseases such as GERD and IBD.

The largest market segment is GI Endoscopes/Videoscopes (flexible and rigid), while the fastest growing segments are Capsule Endoscopy and Reprocessed Biopsy Forceps. HD endoscopes with narrow band imaging are the latest trend with market leaders such as Olympus Medical, Boston Scientific, Cook Endoscopy, Fuji, and Pentax.

1) The global flexible endoscopes market was estimated at $2.4 billion in 2010 and is forecast to grow at a Compound Annual Growth Rate (CAGR) of 4%, to reach $3.1 billion by 2017.  The US flexible endoscopes market, valued at $1 billion in 2010, is forecast to grow by 5% annually during 2010-2017, to reach $1.4 billion by 2017.

Trends in the flexible endoscope market include:

1. Increased Colorectal Cancer (CRC) screening, leading to an increased number of colonoscopies.
2. Natural Orifice Transluminal Endoscopic Surgery (NOTES - natural openings of the body such as mouth, anus, and vagina) is being developed as a less invasive procedure.
3. Flexible Videoscopes, the fastest growing segment, are preferred over fibroscopes in that they allow multiple viewers to the image, as opposed to the surgeon alone. Videoscopes have replaced traditional fibroscopes due to enhanced image quality and the ability to document case information for future reference.

2) The global market for rigid endoscopes was valued at $525.9 million in 2010, and is forecast to reach $684.3 million in 2017, a CAGR of 4%.  The US has the largest market for rigid endoscopes, $176 million in 2010 and itwill continue to dominate at its forecast to reach $232.6million in 2017, a CAGR of 4%.

Rigid endoscopes are used for specific applications such as laparoscopy, hysteroscopy and GI applications, where rigid endoscopes provide greater efficacy as compared to other endoscopes.

Trends in the rigid endoscope market include:

1. Confocal Laser End microscopy - allows gastroenterologists to obtain in-vivo histology of thegastrointestinal mucosa.
   1. Confocal microscopy provides better spatial resolution than conventional fluorescence microscopy.   A blue laser light is used to scan the intestinal mucosa from the surface up to the deepest parts of the mucosal layer.
   2. Series of confocal images within successive planes can be used to observe fine cellular or subcellular structures, and three-dimensional structures in the specimen can be imaged.
2. Endoscopic Ultrasound - endoscope with an ultrasound probe.
   1. The current literature suggests that endoscopic ultrasound is an ideal intraluminal form of staging GI tract malignancies. The ultrasound can look at a tumor within the digestive tract and detect its penetration within the layers of the wall allowing very specific and sensitive diagnostic information as to whether the tumor has spread beyond the serosal wall. Endoscopic ultrasound has been proven to be more sensitive than CT scanning for the staging of esophageal cancer. In addition, it has added value in the staging of rectal cancers.
   2. Extra-luminally, endoscopy ultrasound is now being used to look at lymph nodes surrounding the digestive tract and determining whether malignancies have spread into the lymph node system. In addition, the endoscopic ultrasound device can deploy a thin needle under real-time ultrasonography through the digestive tract wall into lymph nodes. Subsequently, the lymph node can be aspirated for cytologic analysis.

Virtual colonoscopy is no longer reimbursed by Medicare. This will help traditional colonoscopy remain as the gold standard in the US. Reimbursement in Europe is still available.

3) The global capsule endoscope systems market was worth $186.9 million in 2010 and is expected to reach $323.6 million in 2017.    Increased adoption of capsule endoscopy, along with advancements in technology and the availability of High Definition (HD) systems, will drive the global capsule endoscope systems market. Given Imaging has become a key player with its innovative Capsule Endoscopy system.

Reimbursement for capsule endoscopy has contributed to the growth of this market. Initially reimbursement was only for the diagnosis of obscure bleeding of the small bowel by third party payers in countries such as Germany. However, in December 2009, the reimbursement was extended to other diseases of the small bowel, such as suspected Crohn's disease, tumors and other pathologies. Several countries including the UK, France, Sweden and Denmark cover capsule endoscopy for broader indications.

Small intestine pathologies are difficult to diagnose. Capsule endoscopy was proven useful in diagnosing lesions, tumors and other pathologies that are normally hidden inside mucosal layers. Due to the efficacy and efficiency of the capsule endoscope system in this area this resulted in increased physician preference for small bowel investigations.

The Mermaid

Japanese researchers have developed a self-propelled remote controlled capsule endoscope that can "swim" through the digestive tract called the "Mermaid".  

It is the first time a self-propelled endoscope has successfully moved from one part of the digestive tract to another and shot images inside the colon, the team said. The device is about one centimetre (0.4 inches) in diameter and 4.5 (1.8 inches) long and has magnetic driving gear that allows for precise control of its direction and location.

"By remotely controlling the capsule, we can precisely photograph the area which needs to be tested," Osaka Medical College professor Kazuhide Higuchi said. "It can examine the digestive canal from the oesophagus to the colon in a few hours. It reduces burdens on patients and can led to the discovery of cancer," he said.

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