What follows below is a review of some of the biotech and pharma news stories that caught my attention during the month of January 2014. Please also see Protecting IP is NOT ‘Satanic Genocide’, written by Dr. Kristina Lybecker.
All-Oral, Interferon-Free Therapy for the Treatment of Hepatitis C Genotype 1
On January 31, 2014, AbbVie (NYSE: ABBV) announced the completion of its phase III clinical program and released results of four additional studies designed to assess AbbVie’s investigational all-oral, interferon-free therapy with and without ribavirin (RBV) in patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection. These results described below confirm previously reported AbbVie data and further demonstrate high sustained virologic response rates 12 weeks post treatment (SVR12) and tolerability in these GT1 patients. Even in difficult-to-treat patients (cirrhotic patients) achieved 92-96 percent SVR(12) rates.
The AbbVie investigational regimen consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) with or without ribavirin (weight-based), dosed twice daily. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations.
AbbVie is on track to begin major regulatory submissions early in the second quarter of 2014.
FTC Puts Conditions on Endo Health Sciences Acquisition of Boca Life Science Holdings
On January 31, 2014, the FTC announced that pharmaceutical companies Endo Health Sciences Inc. (NASDAQ: ENDP) and Boca Life Science Holdings, LLC and Boca Pharmacal, LLC (Boca) have agreed to a settlement resolving Federal Trade Commission charges that Endo’s acquisition of Boca would be anticompetitive.
According to the FTC’s complaint, Endo’s acquisition of Boca as originally proposed likely would have cause U.S. consumers to pay significantly higher prices for certain generic drugs. The FTC charged that the proposed acquisition would also eliminate one likely future entrant from a very limited pool of future entrants in each of the three other generic drug markets.
According to the FTC, the proposed settlement will preserve competition in the pharmaceutical markets for four prescription generic multivitamin drop products given to children in the United States who do not have access to fluoridated water:
- generic multivitamin drops containing 0.25mg fluoride (generic PolyViFlor 0.25mg drops);
- generic multivitamin drops containing 0.5mg fluoride (generic PolyViFlor 0.5mg drops);
- generic multivitamin drops with 0.25mg fluoride and iron (generic PolyViFlor 0.25mg drops with iron); and
- generic multivitamin drops with 0.25mg fluoride and folate (generic TriViFlor 0.25mg drops).
In addition, the FTC says that the settlement will preserve future competition for three generic drugs:
- generic oral syrup containing brompheniramine maleate (2mg/5ml), dextromethorphan hydrobromide (10mg/5ml), and pseudoephedrine hydrochloride (30mg/5ml) (generic Bromfed-DM), which is used to treat symptoms of the common cold;
- generic oral solution containing hydrocodone (10mg/15ml) and acetaminophen (325mg/15ml ) (generic Zamicet), which is used to relieve moderate to severe pain; and
- generic acetic acid, glacial (2%) with hydrocortisone (1%) ear drops (generic Vosol HC), which are ear drops prescribed to treat “Swimmer’s Ear.”
Conditional Approval for Treatment of T-cell Lymphoma in Dogs
Aratana Therapeutics, Inc. (NASDAQ: PETX), a pet therapeutics company that focuses on the development and commercialization of innovative biopharmaceutical products for cats, dogs and other companion animals, announced on January 28, 2014, that the United States Department of Agriculture (USDA) granted conditional approval for AT-005, Aratana’s canine-specific monoclonal antibody against CD52, which is intended as an aid in the treatment of T-cell lymphoma in dogs. AT-005 is Aratana’s second Canine Lymphoma Monoclonal Antibody to receive conditional approval and it represents Aratana’s first internal commercial opportunity. The company’s canine B-cell lymphoma therapy, AT-004, received conditional approval from the USDA in 2012 and was licensed to Novartis Animal Health Inc. for commercialization in United States and Canada.
Aratana’s canine-specific antibodies against CD20 (AT-004) for B-cell lymphoma and CD52 (AT-005) for T-cell lymphoma are directed against the same molecular targets as leading biologic drugs that are now the standard of care for treating human B-and T-cell lymphoma (Rituxan® and Campath®, respectively). The paradigm shift toward adding targeted biologic therapies for treating cancer, and the success of Rituxan and Campath in particular, serve to validate and de-risk Aratana’s approach to this attractive market.
These products are intended to be available to specialist veterinary practices, so pet owners should consult with their veterinarians about how to access this novel treatment option. The products will be distributed under conditional license based on USDA requirements for demonstration of safety and reasonable expectation of efficacy.
Favorable Markman Ruling for Dopomed in GRALISE® Patent Litigation
Depomed, Inc. (NASDAQ: DEPO) announced today a favorable “Markman” claim construction ruling by Judge Joel A. Pisano of the United States District Court for the District of New Jersey in Depomed’s ongoing patent infringement case against filers of three Abbreviated New Drug Applications (ANDAs) seeking to market generic versions of Depomed’s GRALISE® (gabapentin) product prior to the expiration of Depomed’s patents listed for Gralise in the FDA’s Orange Book. Gralise® (gabapentin) is a once-daily treatment approved for the management of postherpetic neuralgia.
In a Markman ruling, the court determines the meaning of disputed patent terms at issue in patent litigation. Judge Pisano’s ruling construed 24 terms in the patents asserted by Depomed in the litigation. As to 23 of the disputed patent terms, the ruling either principally adopted Depomed’s proposed claim construction or the plain and ordinary meaning of the term. The defendants’ proposed construction was adopted as to one patent term that appears in one of the asserted patents.
“We are pleased with the Court’s ruling and remain confident that our Gralise intellectual property will provide significant commercial exclusivity for the product,” said James A. Schoeneck, Depomed’s President and Chief Executive Officer.
Five of the patents, which relate to Gralise and other proprietary formulations of gabapentin, expire between October 2022 and February 2024. The other four patents, which relate to Gralise and other products formulated with Depomed’s Acuform drug delivery technology, expire between 2016 and 2021.
More FDA Woes for Ranbaxy
On January 23, 2014, the U.S. Food and Drug Administration notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug products. The Toansa facility is now subject to certain terms of a consent decree entered against Ranbaxy in January 2012.
This action taken by the FDA against Ranbaxy comes after an FDA’s inspection of the Toansa facility, which concluded on January 11, 2014. The inspection identified significant violations, which included Toansa staff retesting raw materials, intermediate drug products, and finished API after those items failed analytical testing and specifications, in order to produce acceptable findings. The Toansa facility also failed to report or investigate these failures.
The consent decree contains, among other things, provisions to ensure compliance with current good manufacturing practice (CGMP) requirements at Ranbaxy facilities, as well as provisions to address data integrity issues at those facilities. The consent decree was originally entered against Ranbaxy facilities in Paonta Sahib and Dewas, India, but was later amended in September 2013, to add Ranbaxy’s Mohali facility.
Under the consent decree, the FDA has issued an order prohibiting Ranbaxy from:
- distributing in the United States drugs manufactured using API from Toansa, including drugs made by Ranbaxy’s Ohm Laboratories facility in New Jersey;
- manufacturing API at its Toansa facility for FDA-regulated drug products;
- exporting API from Toansa to the United States for any purpose; and
- providing API from Toansa to other companies, including other Ranbaxy facilities, making products for American consumers.
“We are taking swift action to prevent substandard quality products from reaching U.S. consumers,” said Carol Bennett, acting director of the Office of Compliance in the FDA’s Center for Drug Evaluation and Research. “The FDA is committed to ensuring that the drugs American consumers receive – no matter where they are produced – meet quality standards and are safe and effective.”
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Inovio Develops DNA-based Immune Booster to Enhance T-cell Responses
On January 23, 2014, Inovio Pharmaceuticals, Inc. (NYSE: INO) announced that the company has developed a new DNA-based cytokine immune activator, interleukin -33 (IL-33), that in combination with optimized DNA vaccines delivered by electroporation increased the potency and efficacy of the therapeutic response to the DNA vaccines in a preclinical study. The findings of this study reveal that IL-33 could be an effective immune booster when used with Inovio’s products to generate therapeutic immune responses against cancers and chronic viral infections in humans. Inovio has developed a portfolio of patent-protected IL-33 and other immune activators to form combination therapies with its DNA vaccines and immunotherapies with the goal of achieving the greatest possible efficacy against targeted diseases.
A therapeutic vaccine study treating HPV-16 based cancer-bearing mice demonstrated rapid and complete tumor regression after treatment with Inovio’s HPV16 (human papillomavirus type 16) vaccine in combination with DNA-based IL-33. Both were delivered using Inovio’s CELLECTRA® electroporation device. Previous studies have shown that the HPV 16 DNA vaccine alone was able to prevent tumor growth in mice and delay progression or cure mice of tumors. Addition of the IL-33 immune activator resulted in a more rapid and complete regression of established tumors in the mouse model.
The adjuvant/vaccine combination induced potent CD4 and CD8 T cells. Notably, inclusion of the DNA-based IL-33 immune activator significantly increased the magnitude of vaccine-specific CD8 T cell responses. Prior research has demonstrated that CD4 and CD8 T cells are both important in cellular immune responses; however, CD8 T-cells, or killer T cells, are considered especially integral to fighting cancers and chronic infectious diseases.
FDA Allows Marketing of Test to Help Intellectual Disabilities in Children
On January 17, 2014, the U.S. Food and Drug Administration authorized for marketing the Affymetrix CytoScan Dx Assay, which can detect chromosomal variations that may be responsible for a child’s developmental delay or intellectual disability. Based on a blood sample, the test can analyze the entire genome at one time and detect large and small chromosomal changes.
According to the National Institutes of Health and the American Academy of Pediatrics, two to three percent of children in the United States have some form of intellectual disability. Many intellectual and developmental disabilities, such as Down syndrome and DiGeorge syndrome, are associated with chromosomal variations.
“This new tool may help in the identification of possible causes of a child’s developmental delay or intellectual disability, allowing health care providers and parents to intervene with appropriate care and support for the child,” said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “The FDA’s review of the test provides clinical laboratories with information about the expected performance of the device and the quality of the results.”
Fish & Richardson Wins Hatch-Waxman Litigation for Allergan
Allergan, Inc. (NYSE: AGN) recently prevailed in a patent infringement lawsuit against Sandoz Inc., Lupin Ltd., Lupin Pharmaceuticals Inc., Hi-Tech Pharmacal Co., Inc., Watson Laboratories, Inc., Watson Pharmaceuticals, Inc., and Watson Pharma, Inc. On January 14, 2014, the U.S. District Court for the Eastern District of Texas ruled that the defendants could not sell generic versions of Allergan’s popular LUMIGAN® (bimatoprost ophthalmic solution) 0.01% until Allergan’s last patent expires in 2027.
LUMIGAN® 0.01 is a leading treatment for elevated eye pressure in people with glaucoma or ocular hypertension. LUMIGAN® 0.01% was first approved by the FDA in 2010.
Under Hatch-Waxman, drug companies may file a so-called abbreviated new drug application (ANDA) with the FDA to seek approval for generic versions of already-approved drugs by submitting bioequivalence studies instead of clinical studies, which is a much cheaper method than the normal FDA process. Branded companies that own the patents and believe the generic will infringe must then sue to enforce their patent rights to attempt to prevent the approval of the infringing generic.
As part of the ruling, the court permanently enjoined the defendants from the commercial manufacture, use, offer to sell and/or sale of their proposed generic products in, as well as the import of those products into, the U.S. or its territories.
“We are very pleased for our client Allergan and to have had the privilege of representing them in this case,” said Jonathan Singer, head of the Life Sciences Litigation practice at Fish & Richardson who, along with Juanita Brooks and Douglas McCann, led the litigation and trial effort for Allergan. “This is a victory for all companies that put their R&D dollars into developing new and important products that address the unmet medical needs of patients around the world.”
Mylan Launches Generic Myfortic®, Gets 180 Day Exclusivity
Mylan Inc. (NASDAQ: MYL) announced on January 9, 2014, that its U.S. based subsidiary Mylan Pharmaceuticals Inc. launched Mycophenolic Acid Delayed-release Tablets, 180 mg and 360 mg. This product is the generic version of Novartis’ Myfortic® Delayed-release Tablets.
Mylan was the first company to have filed a substantially complete Abbreviated New Drug Application (ANDA) containing a Paragraph IV patent certification for Mycophenolic Acid Delayed-release Tablets, 360 mg, and was awarded 180 days of marketing exclusivity for this strength. The company received final approval from the U.S. Food and Drug Administration (FDA) for its ANDA for this product.
Mycophenolic Acid Delayed-release Tablets, 180 mg and 360 mg, had U.S. sales of approximately $306.8 million for the 12 months ending Sept. 30, 2013, according to IMS Health. Mycophenolic Acid Delayed-release Tablets are indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant and for the prophylaxis of organ rejection in pediatric patients 5 years of age and older who are at least 6 months post kidney transplant.
Kava Plant May Prevent Cigarette Smoke-induced Lung Cancer
New research from the University of Minnesota College of Pharmacy and Masonic Cancer Center has found that consumption of the root of Piper methysticum, or kava, a plant native to the South Pacific Islands, may prevent the development of tobacco smoke-induced lung cancer.
In addition, the research team has identified the naturally occurring components of kava that appear responsible for all the cancer-preventative benefits. By using a patent-pending blend of these active kava ingredients, the research team was also able to avoid liver damage, a rare side effect previously associated with various commercially available kava-containing dietary supplements.
In the latest study, the University of Minnesota research team found daily consumption of a kava-derived dietary supplement prevented the formation of 99 percent of tumors in a mouse lung tumorigenesis model that is routinely used in predicting lung cancer behavior in humans. The unprecedented level of tumor prevention was coupled with the finding that some mice developed no tumors at all. DNA damage resulting from tobacco carcinogens was also significantly reduced by way of prevention, providing a clue to what is potentially behind kava’s effectiveness.
According to Stefan Gafner, Chief Science Officer of the nonprofit American Botanical Council, “The fact that the researchers were able to find evidence of the ability of a kava fraction to prevent the formation of tumors in mice, in support of epidemiological data showing a lower incidence of lung cancer in people living on the South Pacific Islands where kava is traditionally used, makes this study very compelling. If confirmed in human clinical studies, the results could have a big impact on human health and may lead to a greater emphasis on prevention rather than cure.”
While much work still remains these findings suggest the possibility that health care professionals could prescribing kava-derived products in the form of dietary supplements or drugs for current tobacco smokers to reduce their risk of developing lung cancer.
FDA approves Mekinist with Tafinlar for Advanced Melanoma
At the beginning of January the U.S. Food and Drug Administration approved Mekinist (trametinib) in combination with Tafinlar (dabrafenib) to treat patients with advanced melanoma that is unresectable (cannot be removed by surgery) or metastatic (late-stage). The FDA approved the combination of Mekinist and Tafinlar under the agency’s accelerated approval program, which allows the FDA to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. Mekinist and Tafinlar are marketed by GlaxoSmithKline, based in Research Triangle Park, N.C.
In May 2013, the FDA approved both drugs as single agents to treat patients with unresectable or metastatic melanoma. Melanoma is the most aggressive type of skin cancer and is the leading cause of death from skin disease.
Mekinist and Tafinlar are used to block signaling in different sites of the same molecular pathway that promotes cancer cell growth. They are specifically indicated as a combination therapy for patients with melanoma whose tumors express gene mutations called BRAF V600E and V600K. The BRAF protein is involved in the regulation of normal cell growth, but it is mutated in approximately half of melanomas arising from the skin.
“Mekinist and Tafinlar are the first drugs approved for combination treatment of melanoma,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Their development for combination use is based on the strong understanding of the biological pathways of the disease. This approval illustrates the value of continuing to study drugs in combination for clinical development.”
The National Cancer Institute estimated that 76,690 Americans would be diagnosed with melanoma and 9,480 would die from the disease in 2013.
FDA Approves Farxiga to Treat Type 2 Diabetes
On January 8, 2014, the FDA approved Farxiga (dapaglifozin) tablets to improve glycemic control, along with diet and exercise, in adults with type 2 diabetes. Farxiga is marketed by Bristol-Meyers Squibb Company (NYSE: BMY), Princeton, N.J. and AstraZeneca Pharmaceuticals L.P., Wilmington, Delaware, which operates as a subsidiary of AstraZeneca PLC (NYSE: AZN).
Farxiga is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that blocks the reabsorption of glucose by the kidney, increases glucose excretion, and lowers blood glucose levels. The drug’s safety and effectiveness were evaluated in 16 clinical trials involving more than 9,400 patients with type 2 diabetes. The trials showed improvement in HbA1c (hemoglogin A1c or glycosylated hemoglobin, a measure of blood sugar control).
Type 2 diabetes affects about 24 million people and accounts for more than 90 percent of diabetes cases diagnosed in the United States. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness, and nerve and kidney damage.
Cancer, HIV/AIDS Pain Treatment Patented
Drug discovery and development company Snowdon Inc., a Foundation Venture Capital Group portfolio company, has been a patent to treat neuropathic pain. According to company founder Dr. William Welsh, the Norman H. Edelman Professor in Bioinformatics at Rutgers Robert Wood Johnson Medical School, the Glutamate patent enables the use of simple molecules to treat neuropathic pain that arises from common medical conditions including diabetes, shingles, cancer, fibromyalgia, lower back pain and HIV/AIDS.
The Glutamate Receptor Modulators and Therapeutics Agents patent (US Patent No. 8,614,205) identifies a novel family of metabotropic glutamate receptor modulators as potential therapeutic agents for pain, neurological disorders and psychiatric illnesses.