Botox (botulinum toxin type A) injections have gained a substantial amount of popularity as a temporary wrinkle fix, but the benefits of Botox may be more than skin-deep. Allergan (Irvine, California) is pursuing the use of the therapy to treat headaches and migraines.
The company said it has completed a top-line analysis of its two Phase III trials exploring the use of Botox for the prophylactic treatment of headache in adults suffering from chronic migraine those who experience migraine attacks 15 or more days every month. According to Allergan, Botox is the first therapy being investigated for this condition, which is estimated to affect up to 3.6 million people in the U.S.
"We are pleased with the top-line results of our Phase III clinical trials, which show that Botox treatment provided benefit to these patients whose lives have been profoundly impacted by this severely debilitating condition," said Scott Whitcup, MD, executive VP of R&D. "It is gratifying to focus our research and development efforts on an indication that addresses such an important unmet medical need."
Based on this early analysis of the two Phase III clinical trials, Allergan says it hopes to file a supplemental biologics license application (sBLA) with the FDA to use Botox in chronic migraine by the middle of next year. The company said it expects to publish full data results mid-2009.
"In our Phase II clinical trials, we looked at various headache populations, including episodic migraine and chronic migraine," Crystal Cienfuegos, an Allergan spokeswoman, told Biomedical Business & Technology in an e-mail response to questions. "Based on the data, we believe that the chronic migraine sufferer would be the headache segment to most likely benefit from Botox treatment, if approved."
In addition to its cosmetic use, Botox is approved for the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia. The drug also is approved to treat severe primary axillary hyperhirosis that is inadequately managed with topical agents.
In both Phase III clinical trials, patients were randomly assigned to treatment with Botox or placebo injections every 12 weeks. The primary analysis was performed at week 24 following two treatment cycles. The two major efficacy measures evaluated in the trials were change from baseline in the number of headache episodes and number of headache days occurring in the 28-day period preceding week 24. In Allergan's discussions with the FDA concerning the design of the trials, the agency considered number of headache days the preferred efficacy measure for the potential indication, the company noted.
In the first Phase III study, Allergan selected "number of headache episodes" as the primary endpoint for evaluation, with "number of headache days" being the secondary endpoint. Results indicated that although both groups showed a statistically significant improvement from baseline, there was no significant difference in the reduction of number of headache episodes between patients receiving Botox and placebo. However, the study showed a decrease in number of headache days, the FDA's preferred efficacy measure, which was significantly greater in patients receiving the drug compared with those receiving placebo. The decrease in number of migraine/probable migraine days was also found to be significantly greater in patients treated with Botox compared with the placebo group.
Based on the data from the first Phase III trial, the primary endpoint for the second study was changed to number of headache days, with number of headache episodes being a secondary endpoint, before the data were unmasked. In the second Phase III study, the primary endpoint and key secondary endpoints showed statistically significant benefit of Botox treatment over placebo injections, Allergan said. Specifically, patients treated with Botox demonstrated a significantly greater decrease in both number of headache days and number of headache episodes, the company noted. Similar to the first Phase III trial, the second study also showed a decrease in number of migraine/probable migraine days that was significantly greater in the Botox group.
According to Allergan, Botox treatments were well-tolerated in patients suffering from chronic migraine in both Phase III trials. Also, in both studies, an evaluation of quality of life revealed an improvement in quality of life among the Botox patients, the company said.
Elsewhere in the product pipeline:
• Accelr8 Technology (Denver) said that the company and its research collaborators have completed two studies that characterize technical advances for its BACcel rapid diagnostic system, being developed to rapidly identify bacteria and their antibiotic resistance mechanisms. Investigators at the Denver Health Medical Center conducted one of the studies, reviewing the charts of patients who had contracted staph infections, and analyzed the appropriateness of initial treatments prescribed in each case. They analyzed stored bacterial isolates from the same cases, using the BACcel system. "What-if" scenarios projected possible improvements in therapy had the BACcel system's same-day results been available, rather than having to wait two or three days for cultures. The second study used the BACcel system to identify a multi-resistant mechanism known as "ESBL," which includes hundreds of variant enzymes that break down members of the largest class of antibiotics. ESBLs occur in a large family of bacteria that account for approximately 25% to 35% of serious hospital infections. The bacteria include organisms such as E. coli and Klebsiella. Rapid tests for ESBLs do not exist. The new test takes less than four hours to deliver results, and adds the second of three major pathogen and resistance categories to the BACcel system. The new ESBL test joins two tests designed for "staph" infections that the company had previously presented. Accelr8 also plans to add a third category of highly resistant bacteria that includes Pseudomonas and Acinetobacter. This category accounts for as many as one-third of dangerous ICU infections that are difficult to diagnose and treat, according to Accelr8.
• Agendia (Huntington Beach, California/Amsterdam, the Netherlands) reported the launch of TargetPrint, a diagnostic test that allows physicians to quantitatively determine the gene expression levels of the estrogen receptor (ER), progesterone receptor (PR) and Human Epidermal growth factor Receptor 2 (HER2) in breast cancer tumor biopsies. The company said that the accurate measurement of these receptors "is of paramount importance in planning treatment of breast cancer patients after surgery and assists physicians and patients in making informed treatment decisions." TargetPrint runs on the firm's new High Density Chip, which received FDA clearance in August.
• Alcon (Huenenberg, Switzerland) reported the commercial launch outside the U.S. of the new +3.0 Add Power AcrySof ReSTOR Aspheric intraocular lens (IOL). This lens is an improvement to ReSTOR Aspheric platform which is designed for correcting presbyopia in cataract patients. Clinical trials showed that the +3.0 Add Power AcrySof ReSTOR aspheric IOL optimally manages light energy delivered to the retina regardless of the lighting situation to provide patients with high resolution image quality and minimal visual disturbances. At the three-month follow-up exam, 95% of patients had combined distance corrected visual acuities (near, intermediate and distance) of 20/40 or better.
• Alma Lasers (Buffalo Grove, Illinois) reported FDA clearance and the launch of the Pixel CO2, the company's latest fractional, ablative CO2 solution. The system combines the proven effectiveness of an ablative approach with the patient comfort level and convenience of a non-ablative solution. The Pixel CO2 system and recently approved Pixel CO2 Omnifit handpiece have been designed to equip physicians with the company's Pixel Perfect treatment. Pixel Perfect works by creating thousands of microscopic perforations while leaving the skin intact, allowing the skin's top layer to heal rapidly and significantly improving the complexion. Any area of the skin that has surface irregularities can be treated, including the neck, chest, thighs, hands and arms.
• Applied Biosystems (Foster City, California) said it has established a global service provider program for RNA expression analysis. The TaqMan service provider program was created for research scientists who do not have laboratories equipped for performing TaqMan assays, or who choose to outsource their experiments to obtain accurate, sensitive, and reproducible data, generated by authorized third parties using Applied Biosystems' TaqMan RNA expression analysis reagents. This program will provide these scientists with a comprehensive solution for completing a variety of biological sample processing and data analysis projects that incorporate gold-standard TaqMan assay chemistry. Scientists who need higher throughput real-time PCR capabilities or advanced TaqMan solutions can also benefit from having access to these service providers. Applied Biosystems is supporting the TaqMan service provider program by providing reagents, instruments and expertise which are expected to enhance the participating service providers' ability to deliver advanced RNA expression analysis services to customers.
• Assay Designs (Ann Arbor, Michigan) reported the launch a new portfolio of thoroughly characterized ELISA development kits called ImmunoSet. This portfolio of products to assay proteins in various matrices contains the basic components and protocol for the development of five 96-well colorimetric enzyme immunoassays. Assay Designs said it has an aggressive plan for the development and release of the ImmunoSet products, beginning with kits for the detection of mouse and rat heme oxygenase-1 (HO-1) and p53/MDM2 complexes. "With this initial launch of unique antibody sets for our new ImmunoSet product line, Assay Designs is enabling customers with cost effective tools to improve the output of their research," said Dan Calvo, president/CEO. "We will continue to monitor the scientific literature, market trends, and our own antibody sales to expand this important product line as customer demand dictates."
• The Beaumont Commercialization Center (Royal Oak, Michigan) said it is adding a new surgical instrument to its portfolio of medical technology available for licensing. John Uckele, MD, a Beaumont obstetrician/gynecologist, created a surgical instrument for obtaining tissue samples during cervical conization. Cervical conization is a procedure used for the diagnosis, prevention, and treatment of abnormal or pre-cancerous cells in a woman's cervix. If other tests find abnormal or pre-cancerous cells, cervical conization is performed and a cone-shaped sample of the abnormal tissue is removed from the cervix for further examination. Beaumont says that this new device is an improvement over other devices and procedures in that it yields high quality tissue samples, ideal for analysis, with a minimum degree of surgical skill and estimation. The design also helps to reduce the resulting bleeding after the procedure. Part of Beaumont Hospitals, the Beaumont Commercialization Center is a hospital-based medical device development resource focused on helping manufacturers and inventors bring their ideas for new medical devices and technology to reality.
• BSD Medical (Salt Lake City), a maker of microwave systems used primarily in the treatment of cancer, reported FDA clearance for its MicroThermX-100 Microwave Ablation System (MTX-100). The MTX-100 is a small, mobile system that includes a computer, a microwave generator, single-patient-use disposable applicators and a proprietary thermistor-based temperature monitoring system. The delivery of microwave energy is controlled by time and power parameters set by the operator using an interactive touch-screen monitor that allows the operator to control the treatment. The MTX-100 provides minimally invasive access to the target tissue and can be used in open surgical as well as in percutaneous ablation procedures, enabling it to be used by both surgeons and interventional radiologists. It is indicated for use in ablation of soft tissues. BSD said that by using microwaves in treatments the MTX-100 competes head-on with radio frequency ablation technologies that require patient grounding pads.
• Carestream Health (Rochester, New York) reported the introduction of the Carestream DRX-1 system. Carestream said the system, which is in the final stages of development, is expected to greatly reduce the time required to conduct general X-ray exams compared to traditional film/screen systems. A standard patient X-ray exam with multiple images can be captured in less than one minute. The DRX-1 features wireless communications between the imaging components and a console that processes and displays the images and forwards the study to an image and information management system for review, reporting and storage.
• CMS (St. Louis) said that three sites have delivered clinical treatments using Monaco, its intensity modulated radiotherapy (IMRT) treatment planning system. Monaco features biological modeling, constrained optimization and Monte Carlo dose-calculation algorithms. Allegheny General Hospital (Pittsburgh), Erasmus Medical Center (Rotterdam, the Netherlands) and Froedtert Memorial Lutheran Hospital (Milwaukee) all have begun producing treatment plans with the application. Monaco was developed with the University of Tubingen in Germany. Markus Alber, PhD, and colleagues developed the Hyperion project, which is the engine behind the new Monaco system. CMS, an Elekta (Stockholm, Sweden) company, commercialized the concepts and approaches from the Hyperion project to create the foundation for Monaco.
• Cook Medical (Bloomington, Indiana) said it has completed enrollment in the first international clinical trial of a drug-eluting stent designed to treat arterial blockages outside the coronary arteries. The 420 patients enrolled in Cook's randomized trial of its Zilver PTX drug eluting peripheral stent include peripheral arterial disease (PAD) patients treated in Germany, the U.S. and Japan. The Zilver PTX, a self-expanding nitinol stent, uses a polymer-free technology to coat the device with paclitaxel, an antiproliferative drug that has been used successfully to reduce the risk of renarrowing of arteries following angioplasty in coronary disease patients. Cook's ability to adhere the drug to the stent body without using a polymer may be a major clinical advantage, since it eliminates the risk some patients may face due to allergic reactions and other potentially poor outcomes that may be associated with the polymer coatings used on the current generation of drug-eluting coronary stents.
• Digirad (Poway, California) reported the initial clinical trial of a new imaging system using new technology to correct attenuation, or image distortion, an inherent issue in cardiac SPECT imaging. Cardiac SPECT (single photon emission computed tomography) — also called myocardial perfusion imaging — is a non-invasive test to assess the heart's structure and function. Small amounts of radioactive substances are injected into a patient's vein, and special cameras produce images of the heart. These SPECT images are used to identify blockages in coronary arteries, determine whether a patient has had a heart attack, evaluate risk of a heart attack, and assess condition after bypass surgery or angioplasty. The new system, Cardius X-ACT, will be exhibited at the 2008 scientific sessions of the American Society of Nuclear Cardiology, which starts Wednesday in Boston.
• Dilon Technologies (Newport News, Virginia) reported that researchers from Thomas Jefferson University Hospital have released their findings using its new Breast-Specific Gamma Imaging (BSGI) modality at the American Society of Clinical Oncology annual meeting. The authors concluded, "BSGI demonstrates equal sensitivity to breast MRI in the detection of malignant and high-risk breast lesions while reducing the rate of indeterminate findings by 50%. BSGI has additional advantages over MRI in that the study generates four to eight images, as compared to up to 1000 images in MRI and can be utilized in all patients including those with ferromagnetic implants or renal insufficiency. In addition, BSGI is conducted at a fraction of the cost per procedure of breast MRI." Dilon's cornerstone product, the Dilon 6800, is a high-resolution, small field-of-view gamma camera, optimized to perform BSGI, a molecular breast imaging procedure that images the metabolic activity of breast lesions through radiotracer uptake.
• Edwards Lifesciences (Irvine, California) has presented new data on the Edwards Sapien transcatheter heart valve with the Ascendra transapical delivery system. The SOURCE trial is designed to evaluate commercial use of the Sapien valve with a prescribed training and proctoring program. It is a registry of procedural and short-term clinical outcomes. The current data reflect 309 cases at hospitals in 12 European countries. Survival at 30 days was 88%.
• Endologix (Irvine, California) said that six-year patient follow-up data from the company's Powerlink system clinical trial supporting the durability of the Powerlink System as a minimally invasive treatment for abdominal aortic aneurysm (AAA) was published in the September issue of the Journal of Vascular Surgery. Highlights from the six-year follow-up of patients treated with the Powerlink System include: 97.9% freedom from AAA mortality; excellent device performance and integrity, with no ePTFE graft failures, no stent fractures, no aneurysm ruptures; remarkably low incidence of secondary procedures to treat Type I endoleak (3.1%) or a limb occlusion (1.6%); and no migration in patients who received the device via an anatomical fixation technique.
• Haemacure (Montreal) reported the positive results of a second pre-clinical study conducted on the use of its lead product candidate, the human fibrin sealant Hemaseel HMN, in preventing the formation of post-surgical adhesions in a bleeding surgical model. The study compared Haemacure's fibrin sealant to untreated controls and also to two major FDA-approved adhesion prevention products: Interceed Absorbable Adhesion Barrier from Ethicon and Seprafilm Adhesion Barrier from Genzyme. Use of Haemacure's fibrin sealant in the presence of blood resulted in a statistically significant reduction in the incidence, extent and severity of adhesions, as compared to the untreated control group, Haemacure said. The sealant also was statistically significantly more effective than both Interceed and Seprafilm.
• Intact Medical (Natick, Massachusetts) said it has received FDA clearance for the Intact Excise XL a larger version of the company's FDA-approved wands, used with the Intact Breast Lesion Excision System (BLES). As with the Intact BLES, the Intact Excise XL procedure involves the insertion of a slender wand through a small incision in the breast to remove an intact sample of suspicious tissue for histopathologic analysis. The procedure can be performed in an office-based or outpatient setting, with the actual capture of the breast lesion completed in less than 20 seconds. Intact makes minimally invasive systems for the diagnosis and removal of breast lesions.
• Inverness Medical Physician Diagnostics Group (San Jose, California), a division of Inverness Medical Innovations (Waltham, Massachusetts) reported the launch of the INRatio2 PT/INR monitoring system, a portable device that measures blood-clotting time, also known as prothrombin time, using one drop of blood from a patient's finger. The INRatio2 is used by healthcare professionals and their patients in the management of warfarin, a blood-thinning drug, to monitor the effectiveness of the drug and warn of potential blood clots and other bleeding risks. The INRatio2 PT/INR has been cleared by the FDA for warfarin patients to test themselves at home, offering patients quick access to their PT/INR results. The test results are then transmitted to their treating physician by telephone or Internet.
• Masimo (Irvine, California) reported the limited release of its noninvasive and continuous hemoglobin and oxygen content monitors, Radical-7 and Rad-87. Masimo also reported FDA clearance of its latest Rainbow family of adhesive sensors capable of noninvasively measuring total hemoglobin and oxygen content, along with oxygen saturation, pulse rate, pleth variability index and methemoglobin, for use with Masimo Rainbow SET-enabled devices. Masimo noninvasive total hemoglobin and oxygen content are part of Masimo Rainbow SET Pulse CO-Oximetry, a technology platform to noninvasively measure blood constituents and fluid responsiveness that previously required invasive procedures. Masimo makes pulse CO-oximetry and measure-through-motion and low-perfusion pulse oximetry.
• Micrus Endovascular (San Jose, California) reported the initiation of the worldwide launch of its Neuropath guide catheter line. The Neuropath guide catheter line is designed with a flexible and visible tip that allows for ready vascular access, while maintaining good stability. This design is intended to allow neurointerventionalists with better vessel access and greater vessel selection in treating patients with complex anatomies. "The Neuropath marks our entry into the guide catheter market and therefore represents a 100% incremental revenue opportunity for us," said CEO/Chairman John Kilcoyne, CEO/chairman. "The Neuropath is another example of Micrus' commitment to the development of products that deliver clinical advantages to our physicians while bolstering our non-embolic product portfolio." Micrus Endovascular makes implantable and disposable medical devices for treatment of cerebral vascular diseases.
• Nomir Medical Technologies (Waltham, Massachusetts) reported the presentation of positive in vitro and in vivo human data for its Noveon direct optical energy device for treating toenail fungus (onychomycosi). The studies demonstrated that treatment with the Noveon resulted in complete photo-inactivation of the fungi that cause onychomycosis at safe energy densities and temperatures. Nomir received FDA clearance to use Noveon during contact and non-contact surgical procedures of the skin, subcutaneous tissues and nasal passages in dermatology, plastic surgery, podiatry, and otolaryngology.
• Novare Surgical Systems (Cupertino, California) reported the completion of a series of single-port Lap-Band procedures that results in reduced scarring and less postoperative pain for patients. The Lap-Band adjustable gastric banding system is a silicone band that is surgically placed to reduce the amount of food a patient can hold in his or her stomach. The band helps patients control food intake and supports long-term, sustainable weight loss. Although this procedure is performed laparoscopically, it typically requires at least five abdominal incisions. Single Port laparoscopy is an advanced minimally invasive approach in which the surgeon operates exclusively through a single entry point, typically the patient's bellybutton. All of the instruments necessary for the surgery are used through this single incision. After surgery, the scar is almost completely hidden inside the bellybutton.
• Nuance Communications (Burlington, Massachusetts) has introduced its Dragon Medical 10 medical speech recognition software. Dragon claims the new software recognizes dictation nearly twice as fast as its previous release and yields an accuracy improvement of more than 20% over the previous release. The company said Dragon Medical 10 is the only Dragon NaturallySpeaking edition that enables clinicians to dictate directly into an electronic medical record (EMR) system, and rapidly edit and sign medical reports, speeding data input, reducing clicking and typing and, in turn, accelerating EMR use. Dragon Medical can be integrated with any Windows- or Citrix-based EMR system, including, but not limited to, those from Allscripts, Epic, Misys, GE Healthcare, NextGen, Siemens, eClinicalWorks, Meditech, McKesson, Cerner and Eclipsys. Nuance Communications makes speech and imaging solutions for business and consumers.
• PathoLase (Chico, California) said that a select group of podiatrists in several markets in the U.S. are now treating patients who suffer from toenail fungus (onychomycosis) with its laser technology. Using PathoLase's PinPointe FootLaser system, podiatrists in Sacramento and San Jose, California; Salt Lake City and Belleville, New Jersey, are treating their patients' toenail fungus. PathoLase says it has the only medical laser technology currently available in the marketplace that kills the pathogens that cause toenail fungus. The company said it expects to introduce its laser technology into another 20 markets over the next several months.
• Pioneer Surgical Technology (Marquette, Michigan) reported FDA clearance to market FortrOss, a bone graft substitute using nanotechnology for orthopedic applications. The FortrOss bone void filler is a scaffold for the in-growth of new bone and other connective tissues, when superior bone regeneration is required. The osteoconductive matrix in FortrOss uses Pioneer's nanOss technology and is designed to mimic the nanostructures inherent in boney tissue. The combined nanotechnology-based osteoconduction and osteopromotive E-Matrix scaffold of FortrOss positions Pioneer to impact significantly the dynamic field of bone and tissue repair.
• The Sorin Group (Arvada, Colorado) reported the first successful uses in the U.S. of its newest pediatric devices for cardiovascular surgery. The Dideco KIDS D101 pediatric oxygenator and the Dideco KIDS D131 pediatric arterial filter have now been successfully used by Children's Medical Center Dallas during dozens of cardiac surgery procedures for pediatrics. The Dideco KIDS D101 oxygenator is designed to minimize hemodilution and reduce foreign surface area exposure; the D101 is specially proportioned to the pediatric patient. Its low surface area results in a more balanced oxygen and carbon dioxide transfer, and the innovative D101 design has the low priming volume of 87 mls while addressing the cardiopulmonary bypass needs of pediatric patients.
• Siemens Healthcare (Malvern, Pennsylvania) reported that it has received FDA clearance for the Ysio, a digital radiography system with a wireless detector (wi-D) for maximum positioning flexibility. The Ysio can be customized to suit the patient such as one or two detectors, with or without a patient table, and with fully automated or synchronized movements. Ysio can be used as a wall stand with an integrated detector, a wall stand and table system with a wireless detector, or as a mixed detector solution for high throughput and flexibility. The product has 500 different preset examination positions, and a wireless remote will move the X-ray tube into position. Ysio has MaxTouch, an interactive, color touch screen user interface, which supports easy access to key technical factors during examinations. MaxTouch displays easily recognizable icons for speed, accuracy, and access to a comprehensive range of options for adjustment.