What follows below is a review of some of the biotech and pharma news stories that caught my attention during the month of December 2013. I also recommend you take a look at Protecting Data Exclusivity, Protecting the Future of Medicine, written by Dr. Kristina Lybecker.
- Actavis Confirms Generic NuvaRing® Patent Challenge
- Fitch Puts Negative Outlook on Bristol-Myers
- Agios Pharmaceuticals Added to NASDAQ Biotechnology Index
- AstraZeneca Loses at the Federal Circuit on Omeprazole
- Amgen Announces Positive Results From 52-Week Phase 3 Study Of Evolocumab
- Merck and GSK Collaborate on Regimen for Advanced Renal Cell Carcinoma
- Mylan Acquires Rights to LAMA Respiratory Compound from Pfizer
- Mylan Enters Settlement Agreement for First-to-File Generic Version of TARGRETIN®
- Teva and Pfizer Settle Viagra® Patent Dispute
- Everett Laboratories Acquires Quinnova Pharmaceuticals
- Savient Receives Bankruptcy Approval to Sell Assets to Crealta Pharmaceuticals
- FTC Settles with Mylan over Agila Acquisition
- Absorption Pharmaceuticals, Kaiser Permanente Clinical Trial of Promescent®
- Imagenetix Patent Survives Reexamination
- Actavis Announces Agreement on Asacol® HD Patent Challenge Litigation
- FDA Fast Tracks Savara Pharmaceuticals Antibiotic AeroVanc to treat MRSA
- Fitch Gives Johnson & Johnson AAA Rating
- Purdue Pharma, Impax Labs Settle OxyContin Patent Litigation
- Sales of Antiretroviral Drugs for HIV Predicted to Decrease
1. Actavis Confirms Generic NuvaRing® Patent Challenge
On December 24, 2013, Actavis plc (NYSE: ACT) confirmed that its subsidiary, Warner Chilcott Company LLC, filed an Abbreviated New Drug Application (ANDA) with the U.S. Food and Drug Administration (FDA) seeking approval to market Ethinyl Estradiol and Etonogestrel Vaginal Ring, 0.015 mg/24 hour and 0.12 mg/24 hour. Actavis’ ANDA product is a generic version of Merck & Co.’s Nuvaring®, which is an estrogen/progestin combination hormonal contraceptive indicated for use by women to prevent pregnancy.
Merck Sharp & Dohme B.V. filed suit against Warner Chilcott on December 24, 2013, in the U.S. District Court for the District of Delaware seeking to prevent Actavis from commercializing its ANDA product prior to the expiration of U.S. Patent No 5,989,581. The lawsuit was filed under the provisions of the Hatch-Waxman Act, resulting in a stay of final FDA approval of Actavis’ ANDA for up to 30 months from the date the plaintiffs received notice of Actavis’ ANDA filing or until final resolution of the matter before the court, whichever occurs sooner, subject to any other exclusivities.
Based on available information, Actavis believes it may be a “first applicant” to file an ANDA for the generic version of Nuvaring® and, should its ANDA be approved, may be entitled to 180 days of generic market exclusivity.
For the 12 months ending October 31, 2013, Nuvaring® had total U.S. sales of approximately $560 million, according to IMS Health data.
2. Fitch Puts Negative Outlook on Bristol-Myers
Bristol-Myers announced on December 19, 2013, that it has signed an agreement to sell its global diabetes business that was part of its collaboration with AstraZeneca. Under terms of the agreement, AstraZeneca will make an upfront payment of $2.7 billion to Bristol-Myers Squibb, with potential regulatory- and sales-based milestone payments of up to $1.4 billion and will make royalty payments based on net sales through 2025. In addition, AstraZeneca will make payments of up to $225 million if and when certain assets are subsequently transferred. The Bristol-Myers Squibb Board of Directors approved the transaction.
Following this announcement, Fitch Ratings affirmed Bristol-Myers Squibb Co.’s (NYSE: BMY) Issuer Default Rating (IDR) at ‘A-‘ and has revised the Rating Outlook to Negative from Stable. The ratings apply to approximately $6.78 billion of debt outstanding at September 30, 2013.
Fitch also explained that the Plavix and Avapro patent expirations weighed heavily on Bristol-Myers sales, operating margins and cash flows during 2013. Despite a quite year in 2014 relative to patent expirations, Fitch pointed to additional patent expiration pressure on the horizon for Bristol-Myers in 2015 to 2016, which could result in the loss of over 35% of 2013 revenues.
3. Agios Pharmaceuticals Added to NASDAQ Biotechnology Index
Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the fields of cancer metabolism and inborn errors of metabolism, announced on December 23, 2013, that the company has been added to the NASDAQ Biotechnology Index (NASDAQ: NBI).
The NASDAQ Biotechnology Index, launched in 1993, includes securities of NASDAQ-listed companies classified according to the Industry Classification Benchmark as biotechnology or pharmaceutical companies. The NASDAQ Biotechnology Index is calculated under a modified capitalization-weighted methodology and ranked on semi-annual basis.
The NASDAQ Biotechnology Index is the basis for the iShares NASDAQ Biotechnology Index(SM) Fund. All securities in the NASDAQ Biotechnology Index are listed on the NASDAQ Global Market or the NASDAQ Global Select Market, and meet minimum market value and share volume requirements among other criteria.
4. AstraZeneca Loses at the Federal Circuit on Omeprazole
On December 19, 2013, Hanmi Pharmaceuticals received good news in the form of a decision by the U.S. Court of Appeals for the Federal Circuit (CAFC). Invoking 35 U.S.C. §271(e)(2), AstraZeneca had alleged that a drug Hanmi proposed to market falls within claims of U.S. Patent Nos. 5,714,504 and 5,877,192. After the district court construed the claim terms “alkaline salt” in the ’504 patent and “pharmaceutically acceptable salt” in the ’192 patent, the parties consented to the entry of a final judgment of non-infringement based on the constructions.
This appeal presented a single issue: whether the written description limits “alkaline salt” in the ’504 patent to certain specifically named salts. The Federal Circuit held that it does. The Federal Circuit further went on to explain that the written description described the invention clearly and narrowly as including only those salts. The Federal Circuit (per Judge Taranto with Judges Dyk and Moore) summarized its findings as follows: “The written description of the ’504 patent contains a clear disclaimer of claim scope, and no other aspect of the intrinsic record clearly points the other way. We therefore conclude that the district court’s construction of ‘alkaline salt’ was correct, and we affirm the judgment of noninfringement based on that construction.”
The judgment removes a major hurdle for Amneal Pharmaceuticals LLC, a U.S.-based manufacturer of generic pharmaceuticals, which is marketing the product in the U.S. under an exclusive license and distribution agreement with Hanmi. Amneal launched branded Esomeprazole strontium delayed-release capsules 49.3 mg, a 505(b)(2) NDA drug, on December 17.
5. Amgen Announces Positive Results From 52-Week Phase 3 Study Of Evolocumab
On December 19, 2013, Amgen (NASDAQ: AMGN) announced that the Phase 3 DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) study evaluating the long-term safety and efficacy of evolocumab for the treatment of high cholesterol met its primary endpoint of percent reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at week 52.
Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove LDL-C from the blood.
The DESCARTES study evaluated safety, tolerability and efficacy in 901 patients with high LDL-C and a range of cardiovascular risk. Background lipid-lowering therapy was optimized to one of four treatment groups (diet alone; diet plus atorvastatin 10 mg; diet plus atorvastatin 80 mg; and diet plus atorvastatin 80 mg plus ezetimibe 10 mg) for individual patients based on their LDL-C and cardiovascular risk. Patients with a fasting LDL-C ? 75 mg/dL were then randomized to receive monthly subcutaneous evolocumab 420 mg or placebo in combination with background lipid-lowering therapy.
“Data from the Phase 3 DESCARTES study of evolocumab add to the promising safety and efficacy data we recently saw in the MENDEL-2 study and 52-week Phase 2 OSLER study,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “These data contribute to the growing body of research suggesting that evolocumab may offer a new treatment option for patients with dyslipidemia.”
6. Merck and GlaxoSmithKline Collaborate on Regimen for Advanced Renal Cell Carcinoma
On December 18, 2013, Merck (NYSE: MRK) announced the initiation of a clinical trial to evaluate the combination of the company’s investigational anti-PD-1 immunotherapy, MK-3475, and GlaxoSmithKline’s orally administered kinase inhibitor, pazopanib, in advanced renal cell carcinoma.
“Collaborations like this are central to Merck’s strategy to evaluate the potential of MK-3475 for the treatment of cancer,” said Iain Dukes, senior vice president, Licensing and External Scientific Affairs, Merck Research Laboratories. “We look forward to initiating further collaborations to investigate MK-3475 in combination with other anti-cancer agents across a range of tumor types.”
Merck and GlaxoSmithKline entered a collaboration to study MK-3475 with pazopanib and other agents in the GlaxoSmithKline portfolio in the future. This Phase I/II clinical trial is designed to evaluate the safety and efficacy of a combination of MK-3475 and pazopanib in treatment naïve patients with advanced renal cell carcinoma. Further details of the collaboration were not disclosed.
7. Mylan Announces Acquisition of Rights to Novel LAMA Respiratory Compound from Pfizer
On December 18, 2013, Mylan Inc. (NASDAQ: MYL) announced that it has received all regulatory approvals and has completed an agreement with Pfizer for the exclusive worldwide rights to develop, manufacture and commercialize a novel long-acting muscarinic antagonist (LAMA) compound for various indications.
Mylan expects that this product, which is ready to enter Phase IIb, will be submitted to the U.S. Food and Drug Administration (FDA) for approval as a new chemical entity, and expects the product to benefit from long-term patent protection in the U.S. through 2029. Mylan expects to further develop this compound into combination therapies and that these products will utilize the multi-dose dry powder inhaler technology, also licensed from Pfizer.
Mylan CEO Heather Bresch commented, “This acquisition further expands Mylan’s growing respiratory franchise, building upon the products we already have in development, such as our generic Advair® program and our combination product for the treatment of chronic obstructive pulmonary disease (COPD). By adding a novel LAMA compound to our capabilities, we will have the opportunity to bring additional combination products to market, including triple-combination therapies, and further differentiate Mylan as a leader in this important therapeutic area.”
Mylan will have exclusive commercialization rights for this compound in the U.S., Canada, Australia, New Zealand, the European Union and European Free Trade Association countries, India and Japan. In the rest of the world, Mylan and Pfizer will have co-promotion rights to the product. All other financial terms and product details remain confidential.
8. Mylan Announces Settlement Agreement for First-to-File Generic Version of TARGRETIN®
Mylan Inc. (NASDAQ: MYL) announced on December 18, 2013, that its subsidiary Mylan Pharmaceuticals Inc. and partner, Banner Pharmacaps Inc. (a wholly-owned subsidiary of Patheon Inc.), have entered into a settlement and license agreement with Eisai Inc. and Valeant Pharmaceuticals Luxembourg S.a.r.l that will resolve patent litigation related to Bexarotene Capsules, 75 mg. Bexarotene is the generic version of TARGRETIN®, which is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy.
Pursuant to the agreement, the pending litigation will be dismissed, and Mylan and Banner will receive a license to begin selling a generic version of the product on July 9, 2015, or earlier under certain circumstances. All other terms and conditions of the settlement and license agreement are confidential, and the agreement itself is subject to review by the U.S. Department of Justice and the Federal Trade Commission.
Mylan believes that its partner, Banner, is the first company to have filed a substantially complete abbreviated new drug application (ANDA) containing a Paragraph IV certification with the U.S. Food and Drug Administration (FDA) for Bexarotene Capsules, 75 mg. TARGRETIN®, 75 mg, had U.S. sales of approximately $53.6 million for the 12 months ending Sept. 30, 2013, according to IMS Health.
9. Teva and Pfizer Settle Viagra® Patent Dispute
Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) announced on December 17, 2013, that its subsidiary Teva Pharmaceuticals USA, Inc. has entered into an agreement with Pfizer Inc. (NYSE: PFE) to settle patent litigation related to Teva’s generic version of Pfizer’s Viagra® (sildenafil citrate) tablets. Under the terms of the agreement Teva will be able to launch its Abbreviated New Drug Application (ANDA) products pursuant to a royalty-bearing license on December 11, 2017, or earlier under certain circumstances. The terms of the settlement agreement are otherwise confidential.
The U.S. Food and Drug Administration (FDA) has already granted tentative approval for Teva’s generic version of Pfizer’s Viagra® (sildenafil citrate) tablets, 25, 50, and 100 mg. Viagra® had annual sales of approximately $1.2 billion in the United States, based on IMS sales data as of September 2013.
10. Everett Laboratories Acquires Quinnova Pharmaceuticals
Everett Laboratories, Inc., a privately held specialty pharmaceutical company and a subsidiary of Exeltis, headquartered in Madrid, Spain, announced December 16, 2013, that it has acquired Quinnova Pharmaceuticals, Inc. from parent company Amneal Enterprises, LLC.
Lucas Sigman, Chief Executive Officer of Everett Laboratories, said of the acquisition: “We believe dermatology is a very attractive opportunity for Everett in the U.S. market and after an extensive search, we found Quinnova to be a great organization to help us grow this business. Quinnova offers important synergies for Everett with its innovative and entrepreneurial culture, as well as its dedicated and focused sales team, which is similar to Everett. With strong technology platforms and a robust pipeline of new products, we believe with the addition of Quinnova, Everett will accelerate its growth trajectory and be well positioned to become a market leader in women’s health and dermatology in the very near future. In addition, the acquisition provides opportunities for growth for Exeltis by allowing the Company to leverage the Quinnova portfolio of products and technology platform to grow the dermatology business globally.”
Jeffrey S. Day, Quinnova’s President and CEO, stated, “Everett and Quinnova share similar values, culture and corporate vision, making this transaction a perfect fit for both organizations. I am excited about Quinnova becoming a member of the Exeltis family of aligned companies and what this acquisition represents for everyone at Quinnova Pharmaceuticals as well as to the dermatology marketplace. This acquisition allows Quinnova to accelerate key projects in our commercial operations, complete high-potential R&D projects, build out our robust pipeline, and fulfill the Company’s vision for advancing skin and wound care therapeutics for patients.”
11. Savient Receives Bankruptcy Approval to Sell Assets to Crealta Pharmaceuticals
Savient Pharmaceuticals, Inc. (OTC: SVNTQ) (“Savient”) announced today that it has received approval from the U.S. Bankruptcy Court for the District of Delaware (the “Court”) to sell substantially all of the assets of Savient, including all KRYSTEXXA® assets, to Crealta Pharmaceuticals LLC (“Crealta”).
As previously announced, Savient and Crealta have entered into an acquisition agreement through which Crealta would acquire substantially all of the assets of Savient for gross proceeds of approximately $120.4 million. The agreement was reached following an auction conducted pursuant to bidding procedures approved by the Court. According to the terms of the acquisition agreement, Crealta will purchase Savient’s pharmaceutical portfolio, which is highlighted by the chronic refractory gout drug KRYSTEXXA®. Crealta was established in August 2013 in partnership with GTCR, one of the nation’s leading private equity firms.
Having received approval from the Court, the transaction remains subject to certain closing conditions and the termination of the waiting period under Hart-Scott-Rodino. Additional information, court filings and other documents related to this process, is available through Savient’s claims agent, the Garden City Group, at www.gcginc.com/cases/svnt or 866-297-1238.
Skadden, Arps, Slate, Meagher & Flom LLP and Cole, Schotz, Meisel, Forman & Leonard P.A. are serving as Savient’s legal advisors, and Lazard is serving as its financial advisor. Kirkland & Ellis LLP is serving as legal advisor to Crealta.
12. FTC Settles with Mylan over Agila Acquisition
Following a public comment period, on December 12, 2013, the Federal Trade Commission approved a final order settling charges that Mylan, Inc.’s acquisition of Agila Specialties Global Pte. Ltd and Agila Specialties Pvt. Ltd. (collectively, Agila) from Strides Arcolab Ltd. was anticompetitive in 11 injectable generic drug markets. The FTC’s order, first announced in September, requires Mylan and Agila to remedy the proposed competitive concerns in each of these drug markets, as described in the press release announcing the proposed settlement. No comments were received during the public comment period.
According to the FTC’s complaint, in each of the markets, Mylan and Agila were two of only a limited number of current or likely future competitors. The number of suppliers in generic pharmaceutical markets matters because prices generally decrease as the number of competing generic suppliers increases. In addition, the injectable generic products subject to the final order are highly susceptible to supply disruptions caused by the inherent difficulties of producing sterile liquid drugs. The complaint alleged that by reducing the number of competitors in these markets, the acquisition as originally proposed would eliminate important competition and likely lead to higher prices.
The Commission vote approving the final order was 4-0.
13. Absorption Pharmaceuticals and Kaiser Permanente Initiate Clinical Trial of Promescent®
On December 11, 2013, Absorption Pharmaceuticals LLC (AP) in collaboration with Kaiser Permanente announced the initiation of a clinical trial to evaluate the efficacy of Promescent lidocaine spray for men with premature ejaculation (PE). This Phase III, double blind, placebo-controlled, randomized study will measure the intravaginal ejaculatory latency time (IELT) for subjects aged 18 and older.
Promescent is a topical spray that is applied to the penis about 10 minutes prior to sexual activity. Its formula contains a patented eutectic absorption technology, enabling the lidocaine to penetrate the penile skin’s stratum corneum layer to reach the underlying dermal papillae where the nerves reside that control ejaculation latency. Similar to TEMPE (PSD502) and EMLA, but prilocaine-free, Promescent is the only FDA-approved, topical premature ejaculation product with a lidocaine-only eutectic mixture. Its unique formulation and metered dose delivery system provides superior ejaculatory control with minimal side effects.
The Promescent® trial will be conducted at two Kaiser Permanente Southern California medical centers: Los Angeles and San Diego. Over the course of a year, the study will screen approximately 150 subjects with an estimated 20 percent screen failure rate to produce a total of 120 subjects. Subjects who provide written informed consent, meet all eligibility criteria and are enrolled to the study will be randomized to one of two arms: active treatment (Promescent lidocaine spray) or placebo. Each arm will contain 60 subjects stratified by site.
14. Imagenetix Patent Survives Reexamination
On December 11, 2013, Imagenetix, Inc. (OTCBB: IAGXQ) announced that the Board of Appeals for the United States Patent & Trade Office (USPTO) rejected NIKKEN’s effort to invalidate Imagenetix’s U.S. Patent No. 5,569,676, which is titled A method for the treatment of osteoarthritis. The reexamination filed by NIKKEN was in response to Imagenetix’s lawsuit against NIKKEN filed in the United States Federal District Court for the District of Central California. See Imagenetix v. NIKKEN complaint.
On November 27, 2013, Imagenetix requested that its case against NIKKEN be reinstated. In this suit, which was originally filed on April 29, 2011, Imagenetix seeks damages for NIKKEN’s willful infringement of Imagenetix’s patent.
Following a patent examiner’s initial determination of the patent, NIKKEN prematurely — and incorrectly — issued a press release on January 12, 2012 stating: “The United States Patent Office (USPTO) re-examined Imagenetix’s patent No. 5,569,676 and rendered its final decision, rejecting Imagenetix’s patent claim.”
Now that the USPTO has issued its final decision confirming the validity of the patent, NIKKEN has not yet issued a correcting press release notifying its distributors or others of the USPTO decision.
15. Actavis Announces Tentative Agreement Related to Asacol® HD Patent Challenge Litigation
Actavis plc (NYSE: ACT) announced on December 11, 2013, that it its subsidiary, Warner Chilcott Company, LLC, has entered into an agreement in principle with Zydus Pharmaceuticals USA Inc. and Cadila Healthcare Limited to settle all outstanding patent litigation related to Zydus’ generic version of Asacol® HD (mesalamine) delayed-release tablets. The agreement remains subject to preparation and execution of definitive documentation.
Under the terms of the agreement in principle, Warner Chilcott Company will grant Zydus a royalty-bearing license to market its generic Asacol® HD beginning on November 15, 2015 or earlier under certain circumstances, following receipt by Zydus of final approval from the U.S. Food and Drug Administration (FDA) on its Abbreviated New Drug Application (ANDA) for generic Asacol® HD.
Alternatively, if Zydus does not receive FDA approval of its generic Asacol® HD by July 1, 2016, Zydus will be permitted to launch an authorized generic version of Actavis’ product beginning on July 1, 2016. Other terms of the settlement were not disclosed.
16. FDA Fast Tracks Savara Pharmaceuticals Antibiotic AeroVanc to treat MRSA
On December 10, 2013, Savara Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has designated the Company’s lead antibiotic product, AeroVanc, as a Qualified Infectious Disease Product (QIDP) for the treatment of persistent methicillin-resistant Staphylococcus aureus (MRSA) lung infection in cystic fibrosis patients. The company also received Fast Track designation for AeroVanc pursuant to section 506(a)(1) of the Food and Drug Administration Safety and Innovation Act (FDASIA).
The QIDP and Fast Track designation provide AeroVanc access to certain incentives, including priority review associated with a New Drug Application (NDA) submission and an additional five years of exclusivity under the Hatch-Waxman Act upon FDA approval of AeroVanc. Last year AeroVanc received orphan designation, which provides the product seven years of market exclusivity, and various other incentives.
“The recent QIDP status forms an important part of our market exclusivity strategy,” says Rob Neville, CEO of Savara Pharmaceuticals. “This designation along with Orphan Drug status, our formulation patent protection and our inhalation device exclusivity creates a very robust protection from competition.”
Savara Pharmaceuticals is currently conducting a nationwide Phase II clinical trial evaluating the safety and efficacy of AeroVanc in CF patients.
17. Fitch Gives Johnson & Johnson AAA Rating
Fitch Ratings has assigned an ‘AAA’ rating to Johnson & Johnson’s (NYSE: JNJ) $3.5 billion senior unsecured notes issuance. The Rating Outlook is Stable. As a part of this rating review Fitch noted that Johnson & Johnson’s pharmaceutical business has weathered significant patent expires and has launched a number of medicines with meaningful sales potential. As such, the business is positioned for long-term profitable growth.
18. Purdue Pharma, Impax Labs Settle OxyContin Patent Litigation
Purdue Pharma L.P. and Impax Laboratories, Inc. announced on December 3, 2013, that the companies have agreed to resolve the patent infringement lawsuits between them pending in the United States District Court for the Southern District of New York concerning certain Purdue patents, including patents for abuse-deterrent technology, protecting OxyContin® (oxycodone HCl controlled-release) Tablets CII (“OxyContin”). According to the agreement, Purdue and Impax have submitted Consent Judgments to resolve the litigation and Purdue will grant a license to Impax to sell defined quantities of either a generic version or an authorized generic version of reformulated OxyContin tablets starting as early as 2016.
“We are pleased to have resolved this matter in a manner that respects the inventions we have incorporated into the reformulated OxyContin tablets,” said John H. Stewart, President and CEO of Purdue Pharma. “This agreement relieves us of the burden of continued litigation and allows us to focus on providing innovative medications for healthcare professionals and the patients they serve.”
19. Sales of Antiretroviral Drugs for HIV Predicted to Decrease
Decision Resources, a research and advisory firm for pharmaceutical and healthcare issues, predicts that major-market sales of antiretroviral (ARV) drugs for HIV will decrease marginally over the next decade, from an estimated $13.4 billion in 2012 to $13.1 billion in 2022 in the United States, France,Germany, Italy, Spain, the United Kingdom and Japan.
The report titled Human Immunodeficiency Virus (HIV) finds that the strongest factor constraining the HIV therapy market is the generic erosion of numerous key ARV drugs. Increasing availability of generics in cost-constrained markets will inhibit uptake of new, higher-priced agents and is responsible for decreased ARV sales in major pharmaceutical markets, particularly European markets where the impact of generic erosion will be the heaviest. Notably, all three active pharmaceutical agents in the 2012 sales leader, Gilead/ Bristol-Myers Squibb’s single-tablet regimen (STR) Atripla will lose patent protection during the 2012 to 2022 forecast period, paving the way for generic STR prescribing in the major markets.