Top 2018 Patent Expirations
In 2018, dozens of branded pharmaceutical products will lose their patent protections. In the past, patent expirations brought almost immediate generic competition. However, with biosimilar development, a more costly and complicated process, in addition the delays triggered by patent defenses, it is taking longer to see the copycat drugs come to market.
Novartis’ Advair Copy Not Entering the Market in 2018
On Thursday, Novartis held its first quarter earnings conference call where they stated their copy of GlaxoSmithKline’s Advair would not be available in 2018. Novartis had originally hoped to roll the product in the first half of this year, but in February the FDA issued a complete response letter asking for more data instead of approving it. During the earnings call, Novartis’ CEO, Vas Narasimhan, confirmed the company would need to do a “small bridging study” to address the FDA’s concerns.“We would expect to have to do a small bridging study of bioequivalence bridging study, but we don’t view that to be a significant hurdle for what we can see right now. So, our plan will be to get that study started. And as I said stated to be a ready for launch within 2019.” Narasimhan told investors. Advair is particularly difficult for generic drugmakers to copy because they must develop an inhaler device that delivers the medicine correctly into patients’ lungs.
Low Generic Drug Prices Placing Industry into Crisis
In February, the annual generic drug industry conference was held in Orlando where the discussion during one panel turned to plunging drug prices, consolidation among drug-buying groups, and the increasingly cutthroat nature of the business. The generic drug industry, producers of drugs such as antibiotics, arthritis treatments, medicines for diabetes and high blood pressure, supplies almost 9 of 10 drugs prescribed in the United States.
While many health-care products, including branded drugs, those still under patent, typically command big price hikes, that’s not the case with most generics. A deflation tracker developed by researchers at Evercore ISI Research shows generic drug prices are falling about 11 percent a year, while brand-name drugs are rising about 8 percent a year. A few years ago, purchasing groups were formed by members of drug-delivery supply chain to gain more leverage over drugmakers. The consortium has continued to grow in such a way that just four groups now control 90 percent of drug buying in the U.S. In addition, two of those four are joining forces to purchase generic drugs, which likely will lower prices further.
FDA Rejects Novartis’ Rituxan Biosimilar
On Wednesday, Sandoz, a division of Novartis, stated that the FDA issued a complete response letter (CRL) to for its Biologics Licensing Application (BLA) for its biosimilar to Roche’s Rituxan named GP2013. They did not provide details of the agency’s reasoning.
Rituxan was approved in 1997 in the United States for the treatment of follicular lymphoma, diffuse large B-cell lymphoma and chronic lymphocytic leukemia, as well as rheumatoid arthritis.
Sandoz filed its BLA for GP2013 in the U.S. in September 2017, following European approval of the drug in June 2017.
In their statement, Sandoz said it “stands behind the robust body of evidence included in the regulatory submission and is currently evaluating the content of the letter. While disappointed, Sandoz remains committed to further discussions with FDA in order to bring this important medicine to U.S. patients as soon as possible.”
Japan’s Takeda To Buy Shire
On Tuesday, Japanese drugmaker Takeda announced that it had reached a $62 billion deal to buy Ireland-based Shire in the world’s biggest takeover this year. The acquisition will place Takeda into the top 10 pharmaceutical companies.
The company currently has a market value of $33 billion and it will be adding tens of billions to its debt load to fund the acquisition. Takeda is offering Shire shareholders a mixture of cash and stock.
Takeda’s current top selling drugs include Entyvio, used to treat ulcerative colitis, and cancer drug Leuprorelin. Shire focuses on rare diseases, and it sells Adderall, which is used for ADHD.
The combined group will be a leader in gastroenterology, neuroscience, oncology, rare diseases and blood-derived therapies, used for serious conditions such as hemophilia.
Pfizer and Abbvie JAK Drugs Threaten Amgen and Celgene
The use of Janus kinase (JAK) inhibitors is continuing to prove itself against of out-of-class rival anti-inflammatory drugs.
Pfizer’s Xeljanz, which was already approved to treat rheumatoid arthritis and psoriatic arthritis, added a new indication when it was approved to treat patients with moderate to severe ulcerative colitis, a chronic bowel disease, in March.
AbbVie’s upadacitinib is a JAK1 selective inhibitor that is currently being explored in the treatment of rheumatoid arthritis, Crohn’s disease, ulcerative colitis, atopic dermatitis, psoriatic arthritis and axial SpA.
On Tuesday, Bernstein’s Ronny Gal wrote to clients that the makers of drugs for rheumatoid arthritis, including Amgen’s Enbrel, are the ones who really need to watch out as JAK inhibitors have posted “strong” efficacy data in the disease versus other drug classes, and JAKs’ side effects—which can include infections and elevated cholesterol—are “more acceptable” in that setting.
These drugmakers decline “will accelerate as physicians increasingly use JAKi as the second drug after (AbbVie’s) Humira, instead of trying a second aTNF (Enbrel).”
So far, efficacy data for inflammatory bowel disease has only been “decent” in ulcerative colitis and “moderate” in Crohn’s and multiple other classes will hit the market at the same time JAKs do. However, JAKs will still be competition for Celgene, which is developing candidate ozanimod in both ulcerative colitis and Crohn’s. By the time ozanimod could potentially reach the market, Xeljanz should have an 18-month lead in ulcerative colitis, as well as leverage with payers.
In addition to out-of-class rivals, makers of JAK drugs will have one another to worry about as most payers will have at most one member of the class co-preferred and doctors will switch to other classes after trying a single JAK in patients.
“Prices will likely be flat and competition for preferred will likely pit Xeljanz (PFE’s incumbent) and upadacitinib (ABBV) against each other,” Gal wrote, noting that AbbVie’s stellar formulary positioning with Humira could help it gain an edge.
President Signs “Right-to-Try” Bill
On Wednesday, President Trump signed the controversial “right-to-try” bill allowing terminally ill patients access to experimental medical treatments not yet approved by the FDA.
Under FDA regulations, new drugs must go through three phases of clinical trials before becoming commercially available, which often takes years. “Right to try” now allows patients and doctors to ask drug companies directly for access to the experimental drugs that have cleared just the first phase of a trial, rather than wait for approval by the agency.
Opponents of the bill argue that a program known as compassionate use, or expanded access, has been in place since the 1970s and allows patients with a serious disease or condition to try experimental drugs with FDA approval. The FDA currently approves about 99 percent of experimental drug requests.
Supporters say it will provide new treatment opportunities for terminally ill patients who have exhausted existing options.
“The FDA is dedicated to achieving the goals that Congress set forth in this legislation, so that patients facing terminal conditions have an additional avenue to access promising investigational medicines,” FDA Commissioner Scott Gottlieb said.
“With the passage of this bill, Americans will be able to seek cures,” Trump said adding they will finally be given “the right to try.”
Drug Shortages on the Rise
Drug shortages in the United States jumped to 39 last year from 26 in the two preceding years. This is after five years of the number declining.
Medications consistently in short supply include local anesthetics, injectable opioids, ophthalmic diagnostics, and sterile IV fluids used to deliver virtually all drugs used in an emergency department or surgical setting.
Manufacturing problems and quality issues at Pfizer are causing some of the most troubling shortages. Its Hospira unit which is the largest producer of injectable opioid analgesics used in hospitals has suffered production issues tied to changes and upgrades made at a facility in Kansas after the FSA issued a warning letter. Quality issues at another Pfizer plant that also caused the FDA to issue a warning letter disrupted supplies of Mylan’s EpiPen, an autoinjector for lifesaving epinephrine.
The FDA has been working with Pfizer and other drugmakers to deal with the shortage. However, Pfizer expects the supply problem to continue into 2019.
While manufacturing problems are manmade causes of drug shortages, the FDA has also found itself dealing with so-called acts of God when hurricanes ripped through the Caribbean last year, leaving plants in Puerto Rico, of the biggest supplier of IV fluids, without power to produce.
“These shortages greatly impact patient treatment options and require practitioners to make difficult decisions that can compromise care, such as rationing supplies or using less desirable, but more readily available, alternative therapies,” the FDA said in a statement.
On June 15, thirty-one senators from both parties sent a letter to FDA Commissioner Scott Gottlieb acknowledging the strides that have been made but urging him to address “our nation’s ongoing and worsening drug shortage crisis”.
The senators stated that “These are essential products used every day, and for many of them there are no suitable alternatives that are readily available. This can result in suboptimal pain control or sedation for patients, and ultimately limit patient access to the most appropriate care”.