|FDA Approves MannKind's Afrezza; Synageva BioPharma Reports Phase 3 Study Meets Primary Endpoint And Six Secondary Endpoints|
|By Staff and Wire Reports|
|Monday, 30 June 2014 19:36|
The FDA cleared MannKind Corp.'s (NASDAQ: MNKD) Afrezza, a fast-acting form of insulin, for adults with the most common form of diabetes, which affects more than 25 million Americans. Friday's approval comes more than three years after the agency first asked MannKind to run additional clinical studies on the drug.
Demand for diabetes treatments is surging globally as the prevalence of obesity explodes. According to the World Health Organization, roughly 347 million people worldwide have the disease, a chronic condition in which the body either does not make enough insulin to break down the sugar in foods or uses insulin inefficiently. It can lead to blindness, strokes, heart disease or death. In type 2 diabetes, the most common form of the disease, the body does not use insulin properly. Type 1 diabetes is usually diagnosed in children and young adults. In those cases, the body does not produce insulin.
Afrezza, an insulin powder, comes in a single-use cartridge and is designed to be inhaled at the start of a meal or within 20 minutes. MannKind has said that patients using the drug can achieve peak insulin levels within 12 to 15 minutes. That compares to a wait time of an hour and a half or more after patients inject insulin.
The FDA said in its approval announcement that Afrezza is not a substitute for long-acting insulin and is a new option for controlling insulin levels during meals. The agency approved Afrezza with a boxed warning - the strongest type - indicating that the drug should not be used in patients with chronic lung diseases, such as asthma and smoker's cough, due to reports of breathing spasms. The agency is also requiring several follow-up studies looking at the drug's long-term safety, including its impact on the heart and lungs.
Mannkind first submitted the drug to FDA in March 2009. The Valencia, California-based company has no other products on the market and lost more than $191 million last year.
Several other companies have failed to make inhaled insulin work commercially. In 2007, Pfizer Inc. discontinued its inhaled insulin Exubera after it failed to gain ground on the market. In 2008, Eli Lilly & Co. ended its development program, citing regulatory uncertainty.
MannKind shares fell 5.5 percent in regular trading after the FDA's approval announcement but rebounded 70 cents, or 7 percent, to $10.70 in after-hours trading Friday.
Synageva BioPharma Corp. (NASDAQ: GEVA), a biopharmaceutical company developing therapeutic products for rare diseases, announced the global, randomized, double-blind, placebo-controlled Phase 3 ARISE trial of sebelipase alfa in 66 children and adults with lysosomal acid lipase deficiency (LAL Deficiency) met the primary endpoint of normalization of alanine aminotransferase (ALT), a marker of liver injury (p=0.027). In addition, sebelipase alfa significantly improved multiple other disease-related abnormalities as measured by a number of secondary endpoints.
LAL Deficiency patients enrolled in the trial presented with multiple clinically important abnormalities at baseline. Fibrosis and/or cirrhosis was documented in 100% (32/32) of patients who had baseline biopsies even though the median age of patients enrolled in the trial was only 13 years. Dyslipidemia was common at baseline, with a median LDL cholesterol of 204 mg/dl (which is in the very high category of >190 mg/dl), and an abnormally low median HDL cholesterol of 32.5 mg/dl.
Impact on Dyslipidemia. In addition to demonstrating a statistically significant improvement in ALT normalization, sebelipase alfa improved dyslipidemia with statistically significant reductions in LDL cholesterol (p<0.001), non-HDL cholesterol (p<0.001) and triglycerides (p=0.038), as well as a statistically significant increase in HDL cholesterol (p<0.001), all compared with placebo from baseline to the completion of the double-blind treatment period of 20 weeks.
Impact on Other Liver Abnormalities. Statistically significant improvements were also seen in AST normalization (p<0.001) and in liver fat fraction as assessed by multi-echo gradient echo (MEGE) magnetic resonance imaging (MRI) (p<0.001). Paired liver biopsies at baseline and at 20 weeks were available in 26/66 patients. Of these, 63% of patients treated with sebelipase alfa (10/16) had improvement in hepatic steatosis compared to 40% of patients on placebo (4/10). This difference did not reach statistical significance. Although the hierarchical fixed-sequence testing statistical methodology did not allow for a formal assessment of the remaining secondary endpoint, decreased liver volume as assessed by MRI was observed with sebelipase alfa compared with placebo.
Sebelipase Alfa Safety Overview. The sebelipase alfa and placebo arms had a similar number of patients with reported adverse events. Most adverse events during the double-blind treatment period were mild in nature and unrelated to sebelipase alfa. The adverse events occurring in three or more sebelipase alfa treated patients, and which occurred more commonly in treated than placebo patients, were headache (28% versus 20%), pyrexia or body temperature increased (25% versus 23%), oropharyngeal pain (17% versus 3%), nasopharyngitis (11% versus 10%), abdominal pain (8% versus 3%), constipation (8% versus 3%), nausea (8% versus 7%) and asthenia (8% versus 3%). One patient discontinued from the double-blind portion of the clinical trial. This patient experienced a serious adverse event described as an atypical infusion related reaction following treatment with sebelipase alfa. Four patients in the placebo arm and two patients in the sebelipase alfa arm experienced infusion associated reactions during the double-blind portion of the study.
"This global Phase 3 study in children and adults with LAL Deficiency builds upon our earlier insights into both the manifestations of the disease and the impact of sebelipase alfa. The results from this controlled trial demonstrate the effects of sebelipase alfa on a broad range of disease-related abnormalities and are consistent with the ability of enzyme replacement therapy to address the root cause of the disease. We look forward to providing further details of the study at a future medical conference," said Anthony Quinn, MBChB, PhD, FRCP, Executive Vice President and Chief Medical Officer at Synageva.
"The positive Phase 3 results with sebelipase alfa are an important step forward for patients and families affected by LAL Deficiency," said Sanj K. Patel, President and Chief Executive Officer at Synageva. "We will continue to build towards a sustainable and generational company that is committed to helping patients with rare and devastating diseases."
Clinical Trial Design. The ARISE (Acid Lipase Replacement Investigating Safety and Efficacy) trial enrolled 66 children and adults with LAL Deficiency. Patients enrolled in the trial were randomized on a one-to-one basis to every other week infusions of sebelipase alfa (1 mg/kg) or placebo for the double-blind treatment period of 20 weeks. Details of the Phase 3 ARISE trial will be submitted to a future medical conference and for publication.
Together with safety and efficacy data from the Phase 2/3 study in infants with rapidly progressive LAL Deficiency, in which six of the nine infants enrolled met the primary endpoint of survival to 12 months of age, data from this Phase 3 study in children and adults will be used to support global submissions for product registration. Synageva continues to plan to complete submission of a Biologic License Application (BLA) to the U.S. Food & Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for sebelipase alfa for the treatment of LAL Deficiency by the end of the first quarter of 2015.
Aastrom Biosciences, Inc. (Nasdaq:ASTM), the leading developer of patient-specific expanded cellular therapies for the treatment of severe diseases and conditions, today announced that it will be included in the Russell Microcap® Index, according to information posted by Russell Investments on June 27, 2014.
Advaxis, Inc. (Nasdaq:ADXS), a biotechnology company developing cancer immunotherapies, announced that ADXS-cHER2, its proprietary immunotherapy, was featured on CBS New York in a segment focused on encouraging data from a second study combining ADXS-cHER2 with radiation therapy to treat companion dogs with osteosarcoma (bone cancer).
Alliqua BioMedical, Inc. (Nasdaq:ALQA), a provider of advanced wound care products, was added to the U.S. Russell Microcap® Index after the equity markets closed on June 27, 2014 as Russell Investments reconstituted its comprehensive family of global indexes.
athenahealth, Inc.(Nasdaq:ATHN), a leading provider of cloud-based services for electronic health record (EHR), practice management, and care coordination, today announced that it will hold a conference call for investors on Friday, July 18, 2014, at 8:00 a.m. ET.
Baxano Surgical, Inc. (Nasdaq:BAXS), a medical device company focused on designing, developing and marketing minimally invasive products to treat degenerative conditions of the lumbar spine, today announced that the first case utilizing the Avance™ MIS Pedicle Screw System was recently performed by Dr. Sameer Mathur in Cary, NC.
CAS Medical Systems, Inc. (Nasdaq:CASM), leader in medical devices for non-invasive patient monitoring, announced that on Friday, June 27, 2014, the Company entered into a Loan and Security Agreement with General Electric Capital Corporation.
Cellular Biomedicine Group Inc. (Nasdaq:CBMG), a biomedicine firm engaged in the development of new treatments for degenerative and cancerous diseases, today announced the discontinuation of the Company's consulting business segment.
The Cooper Companies, Inc. (NYSE:COO) today announced it has entered into definitive agreements to acquire Sauflon Pharmaceuticals Ltd, a European manufacturer and distributor of soft contact lenses and solutions, in a transaction valued at approximately $1.2 billion.
Dehaier Medical Systems Ltd. (Nasdaq:DHRM), an emerging leader in the development, assembly, marketing and sale of medical devices and sleep respiratory products in China, Dehaier Medical reminds shareholders that it will hold its 2014 Annual General Meeting at 9:00 p.m., Eastern Time, on Monday, July 28, 2014 in Suite 501, Jiuzhou Plaza, 83 Fuxing Road, Haidian District, Beijing 100856 China.
Fate Therapeutics, Inc. (Nasdaq:FATE), a biopharmaceutical company engaged in the discovery and development of adult stem cell modulators to treat orphan diseases, announced today that it has submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for the clinical development of PROHEMA in pediatric patients with inherited metabolic disorders undergoing hematopoietic stem cell transplantation (HSCT).
Greatbatch, Inc. (NYSE:GB) announced today that it will host a conference call on Thursday, July 31, 2014 at 5:00 p.m. E. T. to discuss its financial results for the second quarter 2014 ended July 4, 2014.
iKang Healthcare Group, Inc. (Nasdaq:KANG), the largest provider in China's fast growing private preventive healthcare services market in terms of revenue in 2013, today announced that it has completed 100% acquisition of Shanghai Huajian Clinic Ltd., a well-known middle-to-high end brand in Shanghai's medical examination market. iKang first acquired a 33% equity in Huajian in January 2014, which has been disclosed in iKang's prospectus for its initial public offering, and subsequently acquired the remaining 67% equity in Huajian.
K2M Group Holdings, Inc. (Nasdaq:KTWO), a global medical device company focused on designing, developing and commercializing innovative and proprietary complex spine technologies, techniques and minimally invasive procedures, today announced it has been added to the Russell 2000® Index, Russell 3000® Index and Russell Global Index as part of the annual reconstitution by Russell Investments of its U.S. and global equity indexes on June 27, 2014.
Lipocine Inc. (Nasdaq:LPCN), a specialty pharmaceutical company, today announced that it was added to the Russell Microcap Index when Russell Investments reconstituted its comprehensive set of U.S. and global equity indices on June 27, 2014.
NeoStem, Inc. (Nasdaq:NBS), a leader in the emerging cellular therapy industry, announced today that two of its leading cancer immunotherapy experts, Dr. Andrew Pecora, Chief Visionary Officer, NeoStem; and Dr. Robert O. Dillman, Vice President, Oncology of the Company's wholly-owned subsidiary, NeoStem Oncology LLC., will give presentations at the sub-conferences of the Novel Cancer Therapeutics Summit in Boston, Massachusetts on Monday, July 7.
Prosensa Holding N.V. (NASDAQ: RNA) the Dutch biopharmaceutical company focusing on rare diseases with a high unmet medical need, today announced the appointment of Willem W. van Weperen to the new position of chief commercial officer and the addition of Dr. Annalisa Jenkins to its Supervisory Board.
Rockwell Medical, Inc. (Nasdaq:RMTI), a fully-integrated biopharmaceutical company targeting end-stage renal disease (ESRD) and chronic kidney disease (CKD) with innovative products and services for the treatment of iron replacement, secondary hyperparathyroidism and hemodialysis, today announced that the U.S. Food & Drug Administration (FDA) granted its request for a small business waiver of the Prescription Drug User Fee Act (PDUFA) fee for its New Drug Application (NDA) for Triferic.
Signal Genetics, Inc. (Nasdaq:SGNL), a commercial stage, molecular diagnostic company focused on providing innovative diagnostic services that help physicians make better-informed decisions concerning the care of their patients suffering from cancer, today announced New York State Department of Health approval of its MyPRS (Myeloma Prognostic Risk Signature®) test.
The Spectranetics Corporation (Nasdaq:SPNC) today announced that it has completed the acquisition of AngioScore Inc., a leading developer, manufacturer and marketer of cardiovascular, specialty balloons, for $230 million in cash, along with additional contingent commercial and regulatory milestone payments.
Tonix Pharmaceuticals Holding Corp. (Nasdaq:TNXP), a clinical-stage pharmaceutical company focused on common disorders of the central nervous system, was added to the Russell Microcap® Index on June 27, 2014.
TriVascular Technologies, Inc. (Nasdaq:TRIV) today announced the company was added to the Russell 2000 and Russell 3000 Indexes following the reconstitution of Russell Investment Group's family of U.S. indexes after market close on June 27, 2014.
XOMA Corporation (Nasdaq:XOMA), a leader in the discovery and development of antibody therapeutics, announced the Company will host a conference call today, Monday, June 30, 2014, at 4:30 p.m. Eastern time to confirm the communication plan for its EYEGUARD™-B clinical program.