Industry Newsletter Updates 1Q2019

Top Drugs Losing Exclusivity in 2019
Many of the drugs are expected to face new generic competition this year and others face uncertainty as they lose some of their IP protections.
Allergan’s Restasis, used for dry-eye, expects competition this quarter as Mylan has an upcoming FDA decision date and approval is expected.  According to a lawsuit filed by four grocery chains last year, Teva, Mylan, Amneal and many other generic drugmakers want to launch generic versions of Restasis. The retailers sued Allergan for an "unlawful scheme" to protect Restasis, saying Allergan made "material misrepresentations" to win follow-up patents as its original IP shields were expiring. If not for those misrepresentations and Allergan's conduct afterward, generics would have rolled out as early as May 2014, the plaintiffs claim.
Amgen’s Sensipar, a calcium reducer, expects competition by midyear or later.  Sensipar's composition of matter patent expired in March 2018, but Amgen is still fighting in court with "a number of generic companies" seeking to market their copies. During the company's fourth-quarter conference call, Chief Financial Officer David Meline said Amgen anticipates litigation "would conclude by around midyear.”  Several copycat drugmakers have already received FDA approvals.
Gilead Sciences’ Epclusa and Harvoni, both used for the treatment of Hepatitis C, have had a generic alternative on the market since January.  Gilead chose to launch generics to its own branded medications only a few years after their FDA approvals.  The company launched a subsidiary called Asegua Therapeutics that rolled out authorized generics to Epclusa and Harvoni earlier this year.
Gilead Sciences’ Letairis, which has been used in the treatment of pulmonary arterial hypertension since 2007, expects a generic version to be launched during the second quarter of 2019.  Gilead has been bracing for competition since a patent expiration last year, but so far, no generic makers have yet received FDA approval for their copycats.
GlaxoSmithKline’s Advair, used in the treatment of asthma and COPD, began facing generic competition in February.  Mylan received FDA approval in late-January and launched in February.  Novartis, which has been looking for FDA approval, recently said it expects a 2020 generic launch rather than 2019. Last year, the FDA rejected a copycat from partners Hikma and Vectura, asking for an additional clinical study.
Indivior’s Suboxone film, used to treat patients with opioid addiction, has generic competition as of February.  Dr. Reddy’s Laboratories launched its copies at risk, despite still-pending patent litigation, and Indivior initially won an injunction to stop the drugmaker's rollout. However, the U.S. Court of Appeals for the Federal Circuit tossed out that injunction.  In early February, the court then denied Indivior’s request to reconsider, allowing Dr. Reddy’s to launch their copycat version.
Pfizer’s Lyrica, used for nerve pain and fibromyalgia, is facing patent expiration on June 30.  First approved by the FDA in 2004, Lyrica was originally set to lose exclusivity at the end of 2018 but Pfizer was granted an additional 6 months of exclusivity from the FDA after testing the drug in pediatric patients. Teva, Mylan, Sandoz, and many other generic companies have tentative approvals ready according to the FDA.
Roche’s Avastin, which has been used in the treatment of metastatic colorectal cancer, nonsquamous non-small cell lung cancer, glioblastoma, and certain other cancers since 2004, expects to have competition within the second half of 2019.  Amgen has already received FDA approval for its Avastin biosimilar, called Mvasi, while Pfizer, Samsung and Celltrion are currently working on copycats.
Roche’s Herceptin, used in the treatment of HER2-positive breast cancer, HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma, is expected to have competition in the second half of 2019.  The drug loses a key patent on June 18 and biosimilars by Celltrion, Samsung and Mylan have already won FDA approval.
Roche’s Rituxan, used for the treatment of blood cancers and rheumatoid arthritis, expects to have biosimilars released within the second half of 2019.  Celltrion and Teva received FDA approval in November for their copycat, called Truxima, but a launch date has not yet been disclosed.  Additionally, Amgen, Pfizer and Sandoz are among those working on developing a Rituxan biosimilar. 


ICER Announces New Drug Pricing Report
The Institute for Clinical and Economic Review (ICER) announced plans to generate an annual report of up to 13 drugs that have experienced substantial price increases over a two-year time period.  The analysis will be called the Unsupported Price Increase (UPI) report.
The UPI report will seek to identify drugs for which there was no new clinical evidence that could support their price increases. These drugs will be identified through research into the 100 drugs with the largest dollar sales in the United States and analysis of wholesale acquisition costs (WAC) to these drugs over the past 24 months. ICER will review changes in the evidence base for these drugs, and report on whether potential evidentiary support for price increases was found.  The group will also ask drugmakers for input on their products' benefits and for other justifications for price increases, such as higher manufacturing costs.
Drugs found to have moderate/high quality new evidence of a substantial improvement in net benefit will be categorized as having a “price increase with new clinical evidence.” Drugs that have no new clinical evidence or clinical evidence that does not meet these criteria will be categorized as having unsupported price increases.

Gilead's Asegua Therapeutics Enters Into Partnership with Louisiana for Hepatitis C
The Louisiana Department of Health and Department of Corrections announced it had selected Asegua Therapeutics to be its partner in the unlimited access, subscription-type model for the treatment of hepatitis C.
Asegua, a subsidiary of Gilead Sciences, will make its medication, the authorized generic of Epclusa, available to hepatitis C patients enrolled in Medicaid and to treat incarcerated patients on an unrestricted basis over the next five years.  By paying a fixed cost for the contract, the state will be able to accurately budget for its spending and prevent future spread of hepatitis C at the same time. For Asegua, the contract offers access to patient groups that are not served by traditional drug funding systems.
Louisiana said it hopes to have a contract signed by June 1 and that the 5-year partnership would start July 1. Louisiana wants to treat more than 10,000 hepatitis C patients on Medicaid and in the state's prisons by the end of 2020. The medication has an overall cure rate of 98 percent across all six main types of hepatitis C.
“Our mission is to enhance public safety. By curing these offenders, we are releasing healthier individuals to the communities, and we are protecting the public by further preventing the spread of the hepatitis C epidemic into Louisiana’s towns and cities,” said James LeBlanc, secretary of the Louisiana Department of Public Safety and Corrections.
“We are excited that Asegua has been selected to partner with the Department of Health and look forward to working on an agreement for this groundbreaking subscription model to increase access to a cure for people living with hepatitis C in Louisiana,” said Gregg Alton, a representative for Asegua. “This is an important step forward on the path to eliminating the virus in Louisiana.”


Novo Nordisk Files for FDA Approval of Oral Semaglutide
Novo Nordisk announced the submission of two New Drug Applications (NDAs) to the FDA for oral semaglutide, a once-daily glucagon-like peptide-1 (GLP-1) analogue in a tablet, as well as a supplemental NDA (sNDA) for once-weekly Ozempic (semaglutide).
The first NDA was submitted seeking approval for its new oral version of semaglutide to control blood sugar in adults with type 2 diabetes. They filed the drug application with a priority review voucher, which will shorten the FDA's review to six months, positioning itself for an approval later this year.
The second NDA for its oral semaglutide seeks approval for an indication to reduce the risk of major adverse cardiovascular events (MACE) such as heart attack, stroke, or death in adults with type 2 diabetes and established cardiovascular disease (CVD) and has an anticipated 10-month review time.

"Achieving glycemic control and managing cardiovascular risk remains a challenge for many adults living with type 2 diabetes," said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. "We are excited about the regulatory filings of the first GLP-1 receptor agonist in a tablet, as we believe oral semaglutide has the potential to further improve the treatment of adults living with type 2 diabetes."
Additionally, Novo Nordisk filed a supplemental NDA for once-weekly injectable semaglutide 0.5 mg or 1 mg, seeking an indication to reduce the risk for major adverse CV events in adults with type 2 diabetes and an established history of CVD. The injectable formulation of the drug was approved by the FDA in December 2017.
“We are very excited about these three regulatory filings with the FDA as they represent a significant milestone for the company, but most importantly represent new potential treatment options for adults living with type 2 diabetes," said Todd Hobbs, vice president and US chief medical officer of Novo Nordisk. "We know that many adults with type 2 diabetes are still struggling to control their blood sugar and are at increased cardiovascular risk. We hope that, if approved, these products can help those patients."

Gilead's Descovy Proves Non-inferior to Truvada for PrEP
Gilead Sciences provided data results that showed that its newer HIV medication, Descovy, proved non-inferior to Truvada in a late-stage trial in the largest HIV prevention study conducted to date.
DISCOVER was a two-year trial that enrolled nearly 5,400 participants at risk for sexually acquired HIV infection. The participants received once-daily regimens of either Truvada or Descovy for HIV pre-exposure prophylaxis (PrEP). The results found seven HIV infections across 2,694 patients taking Descovy and 15 HIV infections across 2,693 participants receiving Truvada. Gilead noted that of the 22 HIV infections reported, five were likely acquired before the patients entered the study.
“As the largest HIV prevention trial conducted to date, the DISCOVER trial results clearly demonstrate Descovy for PrEP achieved a clinical profile similar to the high efficacy of Truvada and a more favorable bone and renal safety profile,” said John McHutchison, AO, MD, Chief Scientific Officer and Head of Research and Development, Gilead Sciences. “We look forward to filing regulatory applications for Descovy for the PrEP indication as a potential important new option to prevent individuals from becoming infected and contribute to the achievement of national and global HIV prevention goals.”
"The very low incidence of HIV in both treatment arms, combined with Descovy’ s improved renal and bone safety as compared with Truvada, demonstrate that Descovy for PrEP may help build on the progress made by Truvada," said Brad Hare, chief of infectious diseases at Kaiser-Permanente.

Novo Nordisk and Abbott Announce Diabetes Partnership
Abbott and Novo Nordisk announced a non-exclusive partnership that will integrate insulin dose data from Novo Nordisk pre-filled and durable connected pens directly into the digital health tools compatible with Abbott’s FreeStyle Libre system.
Abbott's FreeStyle Libre system reads glucose levels through a sensor worn on the back of the upper arm eliminating the need for routine finger pricks.  The FreeStyle LibreLink app enables users to capture and view their real-time glucose levels, their eight-hour glucose history, and how their glucose is currently changing.  The technology links with LibreView, a cloud-based diabetes management system that gives people with diabetes and healthcare professionals reports from major glucose monitoring devices including FreeStyle Libre.
Integrating these two products will enable health care professionals, caregivers and people with diabetes to view glucose and insulin data together to help them make more informed treatment decisions, the two companies noted in their press release.
"Lack of reliable information is a cause of huge frustration for many people with diabetes and their doctors," said Anders Dyhr Toft, corporate vice president, Commercial Innovation, Novo Nordisk. "Together with partners like Abbott, our connected pens will give healthcare professionals a better understanding of a patient's individual diabetes management and can help people with diabetes feel more confident in their treatment."
"It is our aim at Abbott to continuously provide life-changing technology to people living with diabetes," said Jared Watkin, senior vice president, Diabetes Care, Abbott. "Diabetes is a time-intensive condition to manage. People with diabetes must make a variety of decisions every single day about their glucose monitoring, nutrition, insulin and medication intake. By enabling insulin dosing data from Novo Nordisk's connected pens to be shared with our digital health tools, we'll be able to help further eliminate those daily hassles for people, so they have more time to live a fuller, healthier life."
Details regarding a timeline for the new partnership were not released; however, the two companies said they plan to make the integrated solution available for patients as soon as possible.

Patent Challenge of Celgene’s Revlimid Rejected

The U.S. Patent and Trademark Office announced that it had declined to move forward with a patent challenge to Celgene's cancer drug Revlimid from Dr Reddy Laboratories.
Revlimid is a multiple myeloma drug nearing the end of its patent-protection, with protection on its composition of matter set to expire at the end of 2019. A 2015 settlement deal between Celgene and Natco Pharma would allow for limited generic entry beginning in March 2022, and full generic sales permitted at the beginning of 2026.  Dr. Reddy's is seeking to launch a generic version of Revlimid prior to those dates.
The decision makes the prospects of Dr Reddy’s generic entering the U.S. market before 2022 more remote, although there is still ongoing district court litigation between the two parties. In the district court, Dr. Reddy's aims to establish that its generic Revlimid copy does not infringe on another patent held by Celgene that runs through 2027.
Celgene management has said the earliest a potential trial decision could come is the fourth quarter of 2019.
"This does not guarantee that Dr Reddy’s will not seek to invalidate the patents by other means, nor does it mean that Dr Reddy’s will automatically lose in those proceedings," wrote SVB Leerink analyst Geoffrey Porges in a note to investors.  "However, it does mean that the path to early market introduction for Dr Reddy’s is now appreciably slower, and more difficult, as it is for other potential generic filers."

Merck and GSK to Co-Develop Cancer Immunotherapy Treatment
Merck and GlaxoSmithKline (GSK) announced a global alliance to jointly conduct the development and commercialization of M7824, an investigational bifunctional fusion protein immunotherapy.  M7824 is designed to simultaneously target two immuno-suppressive pathways, transforming growth factor-β (TGF-β) trap and an anti-programmed cell death ligand-1 (PD-L1), that are commonly used by cancer cells to evade the immune system.
The treatment is currently in clinical development, including potential registration studies, for multiple difficult-to-treat cancers. Among those studies are a Phase II trial designed to compare M7824 with Merck’s Keytruda as a first-line treatment in patients with PD-L1 expressing advanced non-small cell lung cancer (NSCLC), and several Phase I studies assessing M7824 in solid tumors.
The companies said eight high priority immuno-oncology clinical development studies involving M7824 are ongoing or expected to commence in 2019, including studies in NSCLC and biliary tract cancer.
“Together with GSK we aim to drive a paradigm shift in the treatment of cancer as the leader in this novel class of immunotherapies,” Belén Garijo, member of the executive board and CEO Healthcare of Merck KGaA, declared in a statement. “GSK clearly emerged as the ideal partner due to their strong commitment to oncology, and the complementary talent and capabilities they will bring to our alliance.”
“M7824 brings together two different biological functions in a single molecule, and we have observed encouraging clinical results in treating certain cancer patients, particularly those people with non-small cell lung cancer,” Hal Baron, MD, GSK’s CSO and president, R&D stated. “I’m excited by the potential impact this first-in-class immunotherapy could have on the lives of cancer patients.”

Adamis and Sandoz Launch Alternative to Mylan’s EpiPen
Adamis Pharmaceuticals and their commercial partner, Novartis’ Sandoz announced they had officially launched their Symjepi epinephrine pre-filled syringe in the U.S.  They are launching this medicine as an affordable, single-dose, pre-filled syringe alternative to epinephrine auto-injectors.
"With recent news of epinephrine product shortages in the U.S., we worked together with Sandoz in getting this potentially life-saving quality product into the market as quickly as possible," said Dennis Carlo, chief executive at Adamis, in a statement.
Symjepi’s 0.3 mg injection is indicated for the emergency treatment of allergic reactions (Type 1) including anaphylaxis to stinging and biting insects, allergen immunotherapy, foods, drugs, diagnostic testing substances and other allergens, as well as idiopathic or exercise-induced anaphylaxis. The drug is intended for patients who weigh at least 66 pounds.
The wholesale acquisition cost for a Symjepi two-pack at $250, lower than the $300 price of Mylan’s authorized generic EpiPen and Teva’s generic version.
"The Symjepi device is small in size and fits into the palm of your hand, with the goal of a simple-to-use application and intuitive, user-friendly design," said Carol Lynch, President of Sandoz, said in a statement. "At Sandoz, we strive to reimagine medicine to offer the best care we can in all we do, and having heard from patients, caregivers and healthcare professionals about their eagerness for a new product, we are proud to be a part of the solution to a critical need in the US." 
The product will be made available first in institutions followed by retail settings.  Symjepi’s 0.15 mg injection, which was approved by the FDA in September 2018 to treat patients weighing between 33 and 65 pounds, is expected to be launched soon.

Eli Lilly to Acquire Loxo Oncology

Eli Lilly announced plans to acquire Loxo Oncology, a biopharmaceutical company focused on the development and commercialization of highly selective medicines for patients with genomically defined cancers.
The FDA approved Loxo Oncology's first commercial medicine, Vitrakvi, in November of 2018.  The drug was shown to be effective against a wide variety of cancers driven by a single, rare genetic mutation and is sold in partnership with Bayer.  Lilly stated that the company plans to continue that partnership.
Additionally, Lilly will obtain three of Loxo Oncology’s investigational medicines:
LOXO-292: an oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. The drug has been granted Breakthrough Therapy Designation by the FDA for three indications and could launch as early as 2020.
LOXO-305: an investigational, highly selective non-covalent bruton's tyrosine kinase (BTK) inhibitor. It is currently in in phase 1/2 research for B-cell leukemia and lymphomas.
LOXO-195: a selective TRK inhibitor that is being investigated to address potential mechanisms of acquired resistance that may emerge in patients receiving Vitrakvi or other multikinase inhibitors with anti-TRK activity.
"Lilly Oncology is committed to developing innovative, breakthrough medicines that will make a meaningful difference for people with cancer and help them live longer, healthier lives," said Anne White, president of Lilly Oncology. "The acquisition of Loxo Oncology represents an exciting and immediate opportunity to expand the breadth of our portfolio into precision medicines and target cancers that are caused by specific gene abnormalities. The ability to target tumor dependencies in these populations is a key part of our Lilly Oncology strategy. We look forward to continuing to advance the pioneering scientific innovation begun by Loxo Oncology."
The transaction is not subject to any financing conditions and is expected to close by the end of the first quarter of 2019, subject to customary closing conditions, including receipt of required regulatory approvals and the tender of a majority of the outstanding shares of Loxo Oncology's common stock.


Bristol-Myers Squibb to Acquire Celgene

Bristol-Myers Squibb announced a deal to buy Celgene, joining two of the largest oncology companies.  The combined company would become the fourth largest pharmaceutical company in the United States.
Bristol shareholders will own approximately 69 percent of the combined company, with Celgene shareholders owning 31 percent.
“Together with Celgene, we are creating an innovative biopharma leader, with leading franchises and a deep and broad pipeline that will drive sustainable growth and deliver new options for patients across a range of serious diseases,” Bristol Chairman and CEO Caforio said in a statement. “As a combined entity, we will enhance our leadership positions across our portfolio, including in cancer and immunology and inflammation. We will also benefit from an expanded early- and late-stage pipeline that includes six expected near-term product launches. Together, our pipeline holds significant promise for patients, allowing us to accelerate new options through a broader range of cutting-edge technologies and discovery platforms.”
“For more than 30 years, Celgene’s commitment to leading innovation has allowed us to deliver life-changing treatments to patients in areas of high unmet need. Combining with Bristol-Myers Squibb, we are delivering immediate and substantial value to Celgene shareholders and providing them meaningful participation in the long-term growth opportunities created by the combined company,” said Mark Alles, Chairman and Chief Executive Officer of Celgene. “Our employees should be incredibly proud of what we have accomplished together and excited for the opportunities ahead of us as we join with Bristol-Myers Squibb, where we can further advance our mission for patients. We look forward to working with the Bristol-Myers Squibb team as we bring our two companies together.”
The transaction is subject to approval by Bristol-Myers Squibb and Celgene shareholders and the satisfaction of customary closing conditions and regulatory approvals. The transaction is expected to close in the third quarter of 2019.