BB&T

MannKind (Valencia, California) has confirmed with the FDA the design of two clinical studies that evaluate the efficacy and safety of Afrezza, an ultra rapid-acting mealtime insulin therapy, administered using MannKind's next-generation inhaler.

The FDA had previously asked the company to conduct two clinical trials with the next-generation inhaler (one in patients with Type I diabetes and one in patients with Type II diabetes), with at least one trial including a treatment group using the previously studied MedTone inhaler in order to obtain a head-to-head comparison of the pulmonary safety data for the two devices.

MannKind CFO Matthew Pfeffer said the company recently met with the agency and was “extraordinarily pleased“ with it. “The meeting was everything we hoped it would be and we're really encouraged by the tone of the FDA,“ he said.

Both studies are expected to start in early September, Pfeffer said. “We wanted to make sure we had full agreement with FDA on the design before we started them,“ he said.

Study 171 is an open-label study in patients with Type I diabetes. After a run-in period, during which all patients will be optimized on their basal insulin regimen, subjects will be randomized to one of three arms: a control arm, in which patients use injected rapid-acting insulin at mealtimes, or one of two Afrezza arms, one each for the MedTone and next-generation device. After the mealtime insulin is titrated, there will be a 12-week observation period on stable doses of the mealtime insulin to assess HbA1c levels, which is the primary outcome parameter.

Pfeffer said the new device is “better, smaller, more discreet,“ and overall “much more efficient“ than the MedTone, which was a great device for its time. The device is about the size of a tube of lipstick.

“It's the same powder but it does a more effective job of delivering it to the deep lung,“ Pfeffer said.

Study 174 will assess Afrezza using the next-generation inhaler in patients with Type II diabetes who are inadequately controlled on metformin with or without a second or third oral medication. Patients will be randomized to treatment with Afrezza or placebo. The study will have a titration period, followed by a 12-week observation period to assess HbA1c levels.

Afrezza is a rapid-acting mealtime insulin therapy being developed by MannKind for adult patients with Type I or Type II diabetes for the control of hyperglycemia. It is a drug-device combination product, consisting of Afrezza Inhalation Powder pre-metered into single use dose cartridges and the Afrezza Inhaler. Administered at the start of a meal, Afrezza is designed to dissolve immediately upon inhalation and delivers insulin quickly to the blood stream. Peak insulin levels are achieved within 12 to 14 minutes of administration, mimicking the release of meal-time insulin observed in healthy individuals. To date, the Afrezza clinical program has involved 56 different studies and more than 5,300 adult patients.

“We are very encouraged and pleased with this outcome. Our attention now turns to the execution of these trials,“ said Alfred Mann, chairman/CEO of MannKind. “The protocol for Study 171 has already been sent to institutional review boards and the protocol for Study 174 is being finalized and will be distributed to our sites shortly.“

Pfeffer said the Type I study is a three arm study because it includes a comparative arm with the old device. He said each arm of that trial should enroll about 133 patients, for roughly 500 patients in that non-inferiority study total.

The Type II study will be smaller as it has only two arms and a rather different study design, he noted.

Elsewhere in the product pipeline:

• Apnex Medical (St. Paul, Minnesota) received investigational device exemption approval from the FDA to begin a clinical study to evaluate the safety and effectiveness of its Hypoglossal Nerve Stimulation (HGNS) system to treat obstructive sleep apnea (OSA). The Apnex clinical study is a prospective, randomized, multi-center clinical trial. It is designed to demonstrate the safety and effectiveness of the HGNS therapy in treating patients with moderate-to-severe OSA. To be enrolled in the study patients must not have received lasting benefit from CPAP or other OSA treatments. The Apnex HGNS system is an implantable therapy that is intended to work by activating the muscles in the upper airway to ensure that the airway remains open during sleep. The system detects the patient's breathing and delivers mild stimulation to the hypoglossal nerve, the nerve that controls the muscles of the tongue, to keep the airway open. The stimulation is timed to a patient's own breathing pattern. The HGNS system is designed to work only when the patient is asleep through a handheld controller.

• BSD Medical (Salt Lake City) reported the initiation of hyperthermia treatments, using the BSD-500 Hyperthermia System, at 21st Century Oncology center in Fort Myers, Florida. The initiation of hyperthermia treatments at 21st Century in Fort Myers is a significant event for BSD, as 21st Century Oncology is a provider of radiation therapy centers and operates 98 freestanding and hospital-based centers in the U.S., BSD claims. The BSD-500 Hyperthermia System is used to deliver therapeutic heating (hyperthermia) using either non-invasive (external) hyperthermia, which is delivered using antennas placed over the tumor, or interstitial hyperthermia, which is delivered using antennas that are inserted into the tumor, or a combination of both. The BSD-500 has received FDA PMA approval for the use of hyperthermia alone or in conjunction with radiation therapy for the treatment of certain tumors.

• Cardium Therapeutics (San Diego) reported it completed and submitted supplemental information for its 510(k) application seeking clearance from the FDA to market its Excellagen topical wound care management medical device comprising 2.6% formulated bovine Type I collagen gel for the treatment of dermal wounds. In addition to diabetic foot ulcers, dermal wounds for which Excellagen is intended include partial and full-thickness wounds, pressure ulcers, venous ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds, trauma wounds. The Excellagen kit developed for initial launch consists of a set of four single-use prefilled syringes designed to be applied over a course of up to four treatment procedures. At each treatment procedure, Excellagen is topically applied to the debrided wound, and then covered with a non-adherent dressing.

• Cepheid (Sunnyvale, California) reported the release of an updated Xpert BCR-ABL Monitor test, now reporting results to the International Scale. The test is being released as a European CE IVD Mark product under the European Directive on In Vitro Diagnostic Medical Devices. The test, which runs on Cepheid's GeneXpert System, detects the BCR-ABL mRNA transcript in the peripheral blood of patients with Chronic Myelogenous Leukemia (CML) in about two hours. CML is a cancer of the myeloid lineage of leukocytes (white blood cells) that is characterized by the presence of the “Philadelphia Chromosome,“ a reciprocal translocation of chromosomes 9 and 22 that results in the generation of the BCR-ABL fusion gene. The BCR-ABL protein functions as a constitutively activated Tyrosine Kinase that drives the proliferation of immature myeloid cells. If untreated, CML progresses within several years from a chronic phase to accelerated and blastic phases, with survival in the blastic phase measured in months. The introduction of the targeted Tyrosine Kinase Inhibitors (TKIs) imatinib, dasatanib and nilotinib has had a profound impact on the survival of patients with CML. Since their introduction, CML has been transformed into a chronic condition with good long-term prognosis. Monitoring the levels of BCR-ABL mRNA transcript in the blood of CML patients on TKIs using real-time quantitative PCR has become standard of care in the management of CML.

• Cook Medical (Bloomington, Indiana) reported that physicians will now have access to the Word catheter, a silicone balloon catheter used to treat cysts of the Bartholin gland. Cysts in the Bartholin gland occur when the gland becomes blocked, causing a buildup of fluid in the gland and the formation of a cyst. Cysts vary in size and occasionally become infected, which causes abscesses. Treatment for cysts of the Bartholin gland can include antibiotics, drainage of the cyst or surgical removal of the gland. Once the cyst has been drained, Cook's Word catheter holds the drainage lumen open so the cyst can fully heal without closing again and risking further infection. This is a common procedure often performed in an office setting, and may help reduce the reoccurrence of cysts. The Word catheter includes a silicone balloon that is inserted into the cyst and then inflated to hold the catheter in place and allow the cyst to heal without closing again. Cook's catheter is constructed of silicone, which eliminates the issue of patient sensitivity to latex. To prevent the cyst from closing and refilling again, the catheter can remain in place for up to 28 days while the gland heals.

• Endologix (Irvine, California) reported the first U.S. commercial implant of the company's AFX Endovascular AAA system was performed at Edward Hines, Jr. VA Hospital in Chicago. The procedure was performed by Ross Milner, MD, associate professor and chief of vascular surgery & endovascular therapy at Loyola University. “We are excited to be the first hospital in the U.S. to bring the benefits of the new AFX system to a patient in our local community. The device builds on the compelling clinical evidence supporting Endologix's unique anatomical fixation technology with an enhanced, lower profile delivery system and new graft material. The 17Fr introducer sheath and integrated delivery system make it easy to use in a wide range of patient anatomies. The AFX system performed very well during the procedure; the delivery and deployment of the stent graft was quick and precise, and post-procedure imaging confirmed that the aneurysm was effectively sealed,“ said Miller. Endologix makes minimally invasive treatments for aortic disorders.

• GE Healthcare (Waukesha, Wisconsin) reported FDA clearance of Optima CT660 – a computed tomography (CT) system offering improvements from its predecessors in diagnostic capabilities at low dose levels, and designed for sustainability and ease of use. Powered by GE's CT technologies and applications, this platform is scalable from 32 to 128 slices through purchasable options and enables fast, high performance imaging for patients in a variety of clinical settings, including cardiac, neurological, emergency room and routine CT.

• FRS Custom Solutions (Mansfield, Ohio) has developed a new innovation, called the SoundPOD Wearable AAC System that can help those who have difficulty with speech output and offers a low-cost augmentative alternative communication device. The wearable SoundPOD can wirelessly connect to an iPod or iPad converting off the shelf consumer grade electronics into augmentative communication systems for those who have difficulties generating speech.

• Integra LifeSciences (Plainsboro, New Jersey) reported the introduction of the Zuma-C anterior cervical fixation system, expanding Integra's spine product portfolio with the addition of its first integrated plate and interbody cervical device. Its design is based on the original Zuma platform, which has several years of use in the anterior lumbar spine. Offering a wide variety of implant sizes, combined with a comprehensive set of color-coded instrumentation, it provides an easy-to-use solution for anterior cervical discectomy and fusion, a surgical procedure performed to remove a herniated or degenerative disc in the neck. The Zuma-C system features the benefits of a low-profile anterior fixation plate and a radiolucent interbody in an integrated, user-friendly device, the company said.

• MedShape Solutions (Atlanta) reported the introduction of its new DynaNail intramedullary ankle fusion nail. Ankle fusion is performed to relieve pain in patients with severely degenerative ankle joints, to correct joint deformities or to revise failed total ankle replacements. The DynaNail's design uses shape memory alloy technology to actively adapt to changes, such as local bone resorption, in the arthrodesis (fusion) site. By adapting to such changes, the DynaNail may better maintain close apposition of the bones and compression across the fusion zone during the healing process. Bones in contact with each other and under compressive load heal together faster than bones held apart. The DynaNail device, intended for tibiotalocalcaneal arthrodesis procedures, uses a shape memory internal element that is simply stretched during the insertion procedure. Once the nail is fixed in place with screws, the shape memory alloy element maintains the target fusion bones in close apposition and under sustained compression for longer time periods than static, non-adaptive intramedullary devices. Surgeons implant the DynaNail using a surgical technique similar to that of traditional ankle fusion nails, thereby dramatically reducing the learning curve required for the new technology.

• OraSure Technologies (Bethlehem, Pennsylvania) said it has closed enrollment for its multi-site clinical study of the company's OraQuick Rapid HIV-1/2 test for sale in the U.S. consumer or over-the-counter (OTC) market. As previously reported, OraSure initiated the final phase of clinical testing for an in-home HIV self-test kit in December 2010. This phase consists of a multi-visit, blinded, unobserved user study in which individuals conduct unsupervised oral fluid self-testing using the investigational OTC version of the OraQuick Advance Rapid HIV-1/2 test. Once all subject visits are completed and study results are un-blinded, the performance of the OraQuick Advance Rapid HIV-1/2 Antibody test in an OTC setting will be compared with FDA-approved blood-based assay performance. One of the study objectives specified by the FDA was to identify at least 100 HIV infected, but undiagnosed individuals. In order to meet this requirement, the Company enrolled approximately 5,700 participants in the study across 20 clinical sites nationwide. OraQuick Advance is a rapid point-of-care test that can detect antibodies to both HIV-1 and HIV-2 in 20 minutes, using oral fluid, finger-stick or venipuncture whole blood or plasma specimens.

• Pathwork Diagnostics (Redwood City, California) reported results of a study demonstrating the capability of its Pathwork Tissue of Origin Test to be performed on a variety of body fluid specimens were published online in the peer-reviewed journal Cancer Cytopathology. The Tissue of Origin Test aids in the diagnosis of challenging cancer cases such as those that are metastatic or that have a complex clinical history and is used by leading clinicians around the country. In the study, body fluid specimens prepared in standard formalin-fixed, paraffin-embedded format were generated according to routine protocols. The investigators found that 17 of 27 metastasis-positive fluid specimens yielded sufficient RNA for the Tissue of Origin Test. Of these samples, 94% (16 of 17) were in agreement with the available diagnosis, consistent with results reported for the Tissue of Origin Test in previous validation studies. Pathwork describes its Tissue of Origin Test is the only FDA-cleared and Medicare covered molecular diagnostic test for tissue of origin and has been extensively evaluated in multiple independent studies involving more than 1,100 patient specimens.

• SI-BONE (San Jose, California) reported the launch of the Minimally Invasive Surgical iFuse Implant System in SI Joint FusiON (MISSION) trial to investigate the efficacy of the iFuse implant system. The trial that will examine short- and long-term safety, efficacy, and the economic effectiveness of iFuse when used according to the current product label for sacroiliac joint fusion. The iFuse implant system is intended for treatment of conditions including sacroiliac joint disruptions and degenerative sacroiliitis. The iFuse procedure uses a minimal incision for delivery and implantation of small, titanium implants. The implants are coated with a porous plasma spray that acts as an interference surface, designed to help decrease implant motion. These implants have substantial thickness and sophisticated metallurgy and are able to produce a much stronger construct than that of conventional pins or screws used to surgically fix boney structures.

• Tethys Bioscience (Emeryville, California) reported the publication of study results showing that the PreDx Diabetes Risk Score (DRS) is significantly more accurate than metabolic syndrome in assessing individuals' risk of developing Type 2 diabetes. The results underscore that by enabling more accurate risk stratification, PreDx DRS may be a more valuable clinical tool than metabolic syndrome, and allow physicians to more effectively focus preventive strategies on those patients at the highest risk of disease and who are most in need of urgent intervention. PreDx DRS is a multi-marker fasting blood test that assesses markers of inflammation, fat cell function, and glucose metabolism, and categorizes individuals as low, moderate, or high risk for conversion to diabetes within 5 years. The PreDx DRS provides enhanced risk stratification through the measurement of multiple biomarkers linked to pathways of diabetes progression. PreDx DRS was developed using an approach to quantifying biomarkers suspected of playing roles in diabetes development.

• Toshiba America Medical Systems (Tustin, California) reported its new Vantage Titan 3T open bore MR has received FDA clearance. The new system is the only 3T MR offering patient-friendly features such as noise reduction, a wide and open bore, feet-first imaging and Toshiba's contrast-free techniques, the company said. Toshiba claims some benefits of the Vantage Titan 3T open bore MR include: Vantage Titan's open bore offers a 71 cm aperture. The open bore's larger diameter enables hospitals to scan bariatric patients with greater ease and provides patients with a greater feeling of openness to reduce claustrophobia. Toshiba's exclusive Pianissimo noise-reduction technology, which reduces exam noise by up to 90%, makes the Vantage Titan 3T MR the quietest available and solves one of the 3T market's greatest patient compliance issues. Toshiba is the only imaging vendor to offer advanced contrast-free MRA techniques.

• Ventana Medical Systems (Tucson, Arizona) reported the launch of BenchMark ULTRA with new Ultimate Reagent Access (URA). BenchMark ULTRA with URA is a platform that allows laboratories to process individual immunohistochemistry (IHC) and in situ hybridization (ISH) samples as soon as they arrive in the lab. This enhancement allows labs to quickly respond to unpredictable changes in workflow, improving test turnaround time and reducing stress associated with day-to-day laboratory variability, the company said. URA now completes the total system access of ULTRA, increasing overall slide turnaround time since instrument preparation tasks can be managed while slides are processing. Multi-parameter testing, such as dual and triple stains, may be performed independent of other slides, allowing for rapid patient results.