TrialSite News completes the year with excitement. Founded as a simple and straightforward site to contribute to the cause of transparency in clinical research with a focus on the research site/center, the news site turns six months old on New Year’s Day. The founders couldn’t have predicted the level of interest, which includes the amount of web visits, direct patient feedback and requests for research, information and introductions to investigative sites. As we move to 2019 and complete our first year in operation, we plan on adding many more original content features, curated research news and several other potential value-added services. We will continue to build upon Trial Watch, Site Watch and Price Watch and may introduce new “Watch” sections. Each year we will provide a tier-1 biopharmaceutical intellectual property legal case roundup summarizing relevant recent litigation. 2018 saw a continuation of global biopharmaceutical companies position to protect valuable branded assets—some had better fortune than others in the courts. We include our 2018 report by drug maker ranked by size (as measured in annual sales).
Pfizer recently lost its Lyrica drug patent battle in the UK Supreme Court. Lyrica was originally developed for epilepsy, but additional research demonstrated that it helped patients suffering from neuropathic pain. Consequently, Lyrica evolved into a $5 billion-a-year pain drug. As reported recently by CNBC, the UK’s highest court ruled against Pfizer in its long-running patent battle there. Due to generic competition, Pfizer’s Lyrica sales—driven by the large pain market—will decline by a projected $2 billion. Several generic producers are awaiting patent expiry reports Pharmaceutical-Technology. Lyrica is used to control seizures and treat nerve pain from diabetes, shingles, spinal cord injury and fibromyalgia. The average cost is $438 (with standard discounts) for 60, 75 mg tablets as reported in GoodRx.
Johnson and Johnson (Janssen)
Coming to a court soon is the MorphoSys v. Janssen and Genmab lawsuit as recently reported by Markman Advisors. MorphoSys sued Janssen and Genmab for patent infringement in 2016. Headed to trial in February 2019, German-based MorphSys alleges that Janssen (part of Johnson and Johnson) and Danish Genmab violated three patent claims with their anti-CD38 antibody Darzalex. An anti-cancer drug, Darzalex was originally developed by Genmab and is now part of a co-development effort as Janssen Biotech acquires worldwide commercialization rights. It was given breakthrough drug status in 2013 for multiple myeloma as well as orphan drug status for multiple myeloma, diffuse large B cell lymphoma, follicular lymphoma and mantle cell lymphoma. Genmab announced 2017 Darzalex sales at $1.2 billion as reported by Johnson and Johnson, and Genmab CEO believes peak Darzalex sales could hit $9 billion.
Johnson & Johnson (JNJ) received unwelcome news in the United States District Court, District of New Jersey where the court issued a rule invalidating all asserted claims of a JNJ patent for ZYTIGA. The case involved several companies. JNJ strongly disagreed with the ruling and plans on not only continuing to defend the patent, but also to appeal the decision. The drug is used to treat prostate cancer. Originated in the Cancer Research UK, it was ultimately licensed to Cougar Biotechnology in Los Angeles, California, and JNJ acquired Cougar Biotechnology in 2009. The drug was approved by the FDA in 2011. ZYTIGA annual sales grew from $961 million in 2012 to $2.2 billion in 2014, and sales have hovered at $2.5 billion.
Novartis sued Regeneron earlier in 2018 in U.S. District court for Southern District of New York for patent infringement over the manufacturing process used to make its Eylea and Zaltrap eye treatments. Novartis alleges that they are infringing on its Lucentis patents. Regeneron countered with a response that it believes it has a strong defense.
The U.S. Patent and Trademark Office upheld a Novartis patent concerning Gilenya, a multiple sclerosis blockbuster drug generating over $1.7 billion in 2017. Gilenya is expensive. With one bottle (30 tablets) costing in a range of $5,000 to $8,000 and annual costs exceeding $60,000. Novartis’ victory with the U.S. Patent Office in 2018 triggered multiple suits against generic leaders Mylan, Teva and Sun Pharmaceuticals.
They successfully utilized the Noerr-Pennington doctrine to defend itself against anti-trust violations. The First Circuit Court of Appeals ruled in favor of Novartis dismissing two putative class action lawsuits alleging antitrust violations regarding its prescription drug Gleevac patent. The plaintiffs alleged that Novartis obtained a patent via fraud and then sought to enforce that patent through “sham” patient infringement litigation against genetic drug producers attempting to enter the market. The district court granted Novartis’ motion to dismiss utilizing the Noerr-Pennington doctrine offered the Swiss drug manufacturer immunity from antitrust liability as the plaintiffs failed to plausibly allege either of the two exceptions to that doctrine, including: 1) obtaining a patent through a fraud in the Patent Office, or 2) engaging in “sham” litigation to enforce a patent for anti-competitive purposes. For an excellent brief on the history, see Melinda K. Burton’s article. Gleevac sales totaled $1.9 billion in 2017; the cost of Gleevac can total over $100,000 per year for a patient.
A federal circuit court declined a Roche (Molecular Systems) diagnostic testing patent. Striking a victory for California-based molecular diagnostic venture Cepheid Inc. (now owned by conglomerate Danaher), the court ruled that the patent for the method for detecting tuberculosis should never have been granted to Roche.
Roche won a Chinese patent infringement litigation against Guangzhou Kofa Biotechnology Co. Ltd., Shanghai Xuchi Biotechnology Co., Ltd. and Yuhuan Kangjia Enterprise Co. Ltd. Apparently, Kangjia produced and distributed Roche patented containers to Kofa—which produced and sold reagents in targeted containers to Xuchi for purposes of sales of the infringing reagent containers to laboratories for use on Roche instruments. The case was filed with the Shanghai Intellectual Property Court of the People’s Republic of China in October of 2016. By 2017 the courts declared the Chinese companies to be in violation of Roche patent rights, and in 2018 the Chinese courts ordered compensation for Roche economic loss. The Chinese press have capitalized on this award to showcase China’s “positive step forward in promoting the awareness of domestic intellectual property rights and encouraging innovation.” The concern here is that patent infringement in China is commonplace—the Roche decision may be a positive data point, but it is just one data point.
The valuable Roche Herceptin product line is now at risk. Roche, via its Genentech unit, has sued multiple sponsors over its Herceptin biosimilar. On the World Health Organization’s list of Essential Medicines, Herceptin is a monoclonal antibody used to treat breast cancer-with a focus on HER2 receptor positive. It may be used by itself or together with chemotherapy medication. It was approved for use in the U.S. in 1998 and generated $6.7 billion revenue in 2016 with 90 percent market share for breast cancer (HER2 receptor positive) patients. Costs can total $70,000 per treatment. The patent expired in Europe in 2014 and expires in the U.S. 2019.
In 2018, Roche’s Genentech unit sued Amgen alleging that the latter’s proposed biosimilar would infringe on 37 patents. In 2018 Roche also sued Pfizer to protect its oncology blockbuster and its billions in sales. Roche (Genentech) alleged that Pfizer’s FDA application for its prospective trastuzumab biosimilar infringes on 40 Roche patents. Roche requests compensation for lost sales should Pfizer continue with its product launch prior to the Herceptin patent expiry date of June 2019. Elsewhere, Roche’s Herceptin position is challenged. Roche/Genentech and City of Hope (research center and provider) sued Celltrion, Teva, Amgen, Pfizer and Samsung Bioepis for patent infringement concerning biosimilar Herceptin.
In a 2017 ruling, a UK court ruled against Roche’s attempt to block Herceptin biosimilar competition in the UK. Pfizer subsidiary Hospira won the ability to proceed with Herceptin biosimilar commercialization. More Herceptin biosimilar competition is imminent; however, in 2018 the FDA has rejected three such new drug applications.
The French multinational continues to be active in the courts. Back in late 2017 it launched litigation against U.S.-based Mylan for patent infringement centering on a key blockbuster insulin drug Lantus. At approximately $3.9 billion, it is one of the highest selling diabetes drugs worldwide; however, it is under pressure from sponsors such as Novo Nordisk and Eli Lilly. Recently, the U.S. Patent and Trademark Appeal Board (PTAB) ruled in favor of Mylan. The generic producer reported that Sanofi’s Lantus patent claim was denied. Mylan’s new drug application for generic versions of Lantus is under active FDA review. Mylan co-developed the biosimilar with India’s largest biopharmaceutical company, Biocon. As reported in R&D Magazine, Mylan CEO Heather Bresch noted, “the PTAB’s favorable ruling that invalidates two Sanofi Lantus formulation patents is a crucial step forward in our journey to help address the needs of nearly 30 million Americans living with diabetes.” It would appear that Lantus’ competition is coming to healthcare systems.
The UK-based global pharmaceutical maker has been active on several fronts. Its ViiV Healthcare asset (co-owned with Pfizer and Shionogi) has filed a patent infringement case against Gilead Sciences Inc. in the United States and Canada. The dispute centers on Bictegravir, an investigational new drug of the integrase inhibitor class discovered by Gilead and approved for use in the United States in 2018 for treatment of HIV-1 infection. GSK-majority owned ViiV Healthcare seeks to demonstrate that Gilead’s Bictegravir infringes on the former’s patent covering Dolutegravir and other compounds that include Dolutegravir’s unique chemical scaffold. This lawsuit coincides with GSK’s aggressive moves to dominant multi-billion-dollar HIV drug market. GSK is betting that a shift to using two drugs rather than three will shift the demand toward its treatment plan. Gilead is currently the leader in the HIV drug market which is projected to hit $26 billion by mid-2020’s, according to Deborah Waterhouse, who leads GSK’s majority-owned ViiV Healthcare business. Presently, Gilead maintains a 52 percent market share against GSK’s 22 percent.
In 2018 GSK lost a verdict against Israel’s Teva. In the Coreg patent case, the court ruled against Teva with $235 million judgement. Coreg was initially approved in 1995 and added indications for hypertension, left ventricular dysfunction following heart attack and congestive heart failure in the U.S. In the verdict reversal in the patent carve-out case, the judge ruled that the jury was incorrect to include Teva induced physicians to infringe GSK’s patent. GSK named Emma Walmsley as new CEO in 2017, and during 2018 must implement radical change. The UK giant’s new head had to face the loss of intellectual property rights by focusing on vaccines to mitigate loss of branded sales and strengthen its consumer unit. Under Walmsley, GSK structured the $300 million 23 and Me deal which TrialSite News commented on. GSK makes a bold move here to go directly to 5 million customers for potential drug discovery and development. Will it ultimately pay out? We are probably a long way out from knowing, but will monitor.
In 2018 Merck was hit with a setback in patent infringement litigation with Gilead. Apparently, the U.S. Court of Appeals for the Federal Circuit Court backed a trial judge’s decision to throw out a $200 million jury award concerning patent infringements on hepatitis C medication. The high court found that Merck’s hands were “unclean.” Ultimately, this came down to an interpretation of misconduct on the part of Merck, which included lying under oath by one of its in-house attorneys. Merck is considering any next steps, but this frees up Gilead’s Solvaldi and Harvoni which cure rates are more than 90 percent for Hepatitis C. About 3.2 million are infected with Hepatitis C every year. The conflict originated when the patent at issue was awarded to Idenix Pharmaceuticals, which was acquired by Merck in 2014. When Gilead acquired Pharmasset in 2011, it obtained Sofosbuvir. The ultimate legal dispute centered on whether Pharmasset derived Sofosbuvir from an Idenix patent or whether it developed the compound itself.
Due to ongoing legal pressures from Sanofi, Merck terminated a biosimilar insulin agreement development partnership with Samsung Bioepis in 2018. The New Jersey company analyzed its options given product cost, pricing and competition and concluded to terminate the partnership. Consequently, it had to pay $155 million to cover investments made thus far in the product plus interest payments. It apparently continues other biosimilar collaborations with Bioepis including oncology and immunology.
TrialSite News reported on multiple HUMIRA-related legal issues during the past half-year. The world’s best-selling drug at $18 billion, we provided interesting coverage which raised a few eyebrows. From a purely commercial perspective, AbbVie has executed a brilliant strategy. Its scientists, medical affairs, business development and legal teams are frankly second to none when it comes to creatively collaborating to develop “patent thickets” to preserve future revenues and shareholder value—which of course continues to drive cash flow back into the R&D machinery. For example, AbbVie secured over 100 new patents as part of the intellectual property fortress. They recently announced HUMIRA (Adalimumab) resolutions with Sandoz, Amgen, Mylan and Samsung Bioepis.
Sandoz has been granted a non-exclusive license relating to HUMIRA starting in 2023 when its patent expires. Sandoz will pay royalties to AbbVie for licensing HUMIRA patents—pricing is confidential. Amgen settled with AbbVie for 2023 market entry; a similar resolution was structured with Samsung Bioepis and Mylan. AbbVie has executed a brilliant strategy to keep expanding market share in the U.S. through a series lawsuits and creative deal making. Adalimumab biosimilars are available in Europe since late 2018, enabling the National Health Service in the UK to experience record-breaking cost-savings. The U.S. market will open to biosimilar competition in 2023.
2018 saw personal injury and class action lawsuits filed against Gilead alleging the sponsor be held accountable for actions around its failure to rectify a known defect in tenofovir disoproxil fumerate’s (TDF’s) drug formulation, by knowing a safer alternative (tenofovir alafenamide or TAF) existed, failure to warn of damaging side effects and other allegations. In Malaysia, the government during September this year confirmed it approved “the use of Rights of Government under Patent Act 1983 by exploiting the patented invention of Sofosbuvir 400 mg” as reported in IP Watch. Overall, Gilead has been a market leader in the Hepatitis C market. However, its sales have declined due to a number of factors including 1) the drug’s efficacy in curing most patients on the drug, 2) bolus of patients have ebbed considerably, while 3) new competition has secured growing market share and 4) dropping down prices.
UK-based AstraZeneca filed multiple patent infringement suits in 2018. Recently in India, the British drug maker filed a claim in India via Delhi High Court against Dr. Reddy’s Laboratories to block it from launching generic versions of Brilinta—its leading drug for heart ailments. Brilinta was approved for use in the European Union by the European Commission on December 3, 2010. The drug was approved by the US Food and Drug Administration on July 20, 2011. Brilinta, used to reduce chances of heart attacks or strokes by preventing blood clots in vessels, achieved blockbuster status in 2017 when it raked in over $1 billion in global sales for AstraZeneca. According to an Economic Times article, Dr. Reddy’s generic version was to be marketed as Ticaflo, according to people aware of the development. Dr. Reddy’s has not been an aggressive challenger of drug patents in India.
Over the summer, AstraZeneca settled with the State of Texas for $110 million. The company agreed to settle based on the claims that they cheated the Texas Medicaid program by fraudulently marketing two medications.
Amgen blockbuster Neulasta is a leading white blood cell booster. Sales nearly reached $4 billion in 2017, and intense competition is expected soon. Generic competitors such as Mylan have their sites set. In March 2018, Coherus Biosciences was granted a motion to dismiss an Amgen lawsuit alleging infringement of the Neulasta patent for failure to state claim for which relief could be granted. The court searched back in history and pointed to a transaction where Amgen previously had acknowledged that Coherus did not “literally infringe” on the patent. Dismissal of the suit is a step forward for Coherus, which noted, is close to resubmitting its aBLA for the proposed pegfilgrastim biosimilar (Neulasta). It hopes to launch the biosimilar by mid-2018. In fact, in late 2018 Coherus announced the approval of UDENYCA opening up new competition
Amgen was accused of paying illegal kickbacks to multiple long-term care facility pharmacy providers in return for switching their Medicare and Medicaid patients over to Amgen’s anti-anemia drug Aranesp. The drug’s sales have been declining for over a decade and the company clearly was complicit in allowing creative schemes to bolster sales. The company violated the False Claims Act by paying illegal kickbacks to Omnicare Inc., PharMerica Corp., and Kindred Healthcare Inc. It was initiated by an ex-Amgen employee as a whistleblower.