Achaogen announced that the U.S. Food and Drug Administration’s Antimicrobial Drugs Advisory Committee voted on the two points for Advisory Committee consideration as follows: 1. Has the applicant provided substantial evidence of the safety and effectiveness of plazomicin for the treatment of complicated urinary tract infections? Result: (15-0-0) There were 15 yes votes and zero no votes. No members of the panel abstained. 2. Has the applicant provided substantial evidence of the safety and effectiveness of plazomicin for the treatment of bloodstream infections in patients with limited or no treatment options? Result: (4-11-0) There were four yes votes and 11 no votes. No members of the panel abstained. There were 16 panel members at the meeting, one of whom departed prior to the vote and was therefore not present for the voting.
Wednesday, May 2, 2018
Potentially Fatal Immune Reactions to Seizure, Bipolar Med Draw FDA Warning
FDA warns that lamotrigine (Lamictal) is linked to hemophagocytic lymphohistiocytosis(HLH), a potentially life-threatening immune reaction.
The drug, which is approved for seizures and bipolar disorder, has been on the market for 24 years. For seizures, lamotrigine is used alone or in combination with other drugs in patients 2 years and older. For bipolar disorder, it’s used as a maintenance therapy to delay mania, hypomania or depression.
Reviews of adverse event reports submitted to the FDA as well as cases in the literature turned up a total of eight events worldwide since 1994, five of which were confirmed as HLH. All eight involved hospitalization and one patient died.
“[HLH] can cause severe inflammation throughout the body and lead to hospitalization and death, especially if the reaction is not diagnosed and treated quickly,” the agency said. “As a result, we are requiring a new warning about this risk be added to the prescribing information in the lamotrigine drug labels.”
The condition is characterized by phagocytosis of blood cells and a proliferation of histiocytes in bone marrow and vital organs, including the liver, kidneys, lungs and brain. The reaction can occur within days, or weeks after starting treatment. Patients typically present with persistent fever (>101°F); a physical examination and laboratory tests are needed to diagnose HLH.
Prompt recognition and early treatment are important for improving outcomes in patients with HLH — and for decreasing mortality, the FDA said.
A diagnosis can be established if five or more of the following signs or symptoms are identified:
- fever and rash
- enlarged spleen
- cytopenias
- elevated triglycerides or low blood levels of fibrinogen
- high levels of blood ferritin
- hemophagocytosis identified through bone marrow, spleen or lymph node biopsy
- absent or decreased natural killer (NK) cell activity
- elevated CD25 levels showing prolonged immune cell activation
Lamotrigine should be discontinued if a healthcare provider suspects HLH or another serious immune-related adverse reaction and an alternative etiology cannot be established.
“Diagnosis is often complicated because early signs and symptoms such as fever and rash are not specific,” the FDA’s statement noted. “HLH may also be confused with other serious immune-related adverse reactions such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).”
For patients who experience HLH symptoms while on lamotrigine, immediate medical attention is required. Patients who develop rash or persistent fever should seek prompt evaluation.
Other HLH signs and symptoms include pain, tenderness or swelling in the area of the liver; swollen lymph nodes; jaundice; unusual bleeding; and nervous system problems such as seizures, trouble walking, and visual difficulties or other visual disturbances.
Patients who wish to stop treatment should consult their doctor, as cessation of lamotrigine can lead to uncontrolled seizures or worsening mental health problems, depending on the reason for treatment.
This is not the first safety warning for lamotrigine since its approval. In September 2006 the FDA warned of a possible association of oral clefts in the newborns of mothers who took the drug during pregnancy (more recent reports have called this link into question), in 2008 the agency issued a safety alert related to suicidal thoughts and behavior for all anti-seizure medicines, and in 2010 a meningitis warningfor lamotrigine was issued.
Another drug, alemtuzumab (Lemtrada) for relapsing-remitting multiple sclerosis, has also recently been linked with an increased risk of HLH.
Janssen to Acquire BeneVir, Oncolytic Virus Platform in Deal Worth Up to $1B
Shares of HC2 Holdings, Inc. skyrocketed more than 51 percent in premarket trading today after Janssen Biotech Inc announced it was acquiring Rockville, Maryland-based BeneVir Biopharm, Inc., a subsidiary of HC2 in a deal that could be worth more than $1 billion.
Janssen Biotech, a subsidiary of Johnson & Johnson’s Janssen Pharmaceuticals, cut the deal in order to acquire BeneVir’s proprietary T-Stealth Oncolytic Virus Platform that can be used to develop oncolytic viruses used to infect and destroy cancer cells. The deal was facilitated by Johnson & Johnson Innovation LLC.
Peter Lebowitz, Global Therapeutic Area Head of Oncology at Janssen Research & Development, said oncolytic viral immunotherapy “holds exciting potential” in the treatment of solid tumors. Using oncolytic viral immunotherapy can prime and augment anti-tumor immune responses, he said.
Oncolytic viruses are a growing field in immuno-oncology. Oncolytics have been shown to make a difference in treating various cancers. In 2015 the U.S. Food and Drug Administration approved the first oncolytic virus therapy for melanoma, Amgen’s Imlygic. Multiple companies have jumped into the field, including Merck, which in February acquired Australia-based Viralytics Limited and its oncolytic immunotherapy treatments for $394 million.
The BeneVir T-Stealth platform engineers the oncolytic viruses in order to overcome the body’s immune system. Janssen said it will advance pre-clinical candidates as standalone therapies and in combination with other immunotherapies for the treatment of solid tumor cancers, including lung, prostate, colorectal and more.
“BeneVir’s unique technology platform complements our immuno-oncology research, which is focused on bringing forward an array of novel immunotherapies and combinations that may improve treatment outcomes for patients,” Lebowitz said in a statement.
While Janssen was mum on the financial details of the transaction, HC2 said the deal could be worth up to $1.04 billion when milestones are included. Under the terms of the agreement, Janssen will make an upfront cash payment of $140 million and additional contingent payments of up to $900 million based on achievement of certain predetermined milestones, HC2 announced. The deal is expected to close in the second quarter of 2018.
BeneVir will continue to maintain a research presence in Maryland and become part of the Janssen Oncology Therapeutic Area. The BeneVir team will remain focused on the optimization of next-generation T-Stealth oncolytic viruses in solid tumors and the execution of pre-clinical activities, Janssen said.
Mathai Mammen, global head of Janssen Research & Development, LLC., hailed the addition of the BeneVir team and its scientific platform to the Janssen umbrella.
“We are committed to pursue transformational science from our own laboratories and those of others, as we continue to advance our focus on treating some of the world’s most devastating diseases,” Mammen said.
Top 2018 Biopharma M&A Deals So Far
While the biopharma industry awaits news of an acquisition of Shire by Takeda Pharmaceutical,it’s a good time to take a look back at the bigger deals so far this year. There have literally been dozens of smaller deals, such as Merck acquiring Viralytics for $394 million or Genoptix buyingRosetta Genomics for $10 million, but there have been a handful of bigger deals of note. All this activity is likely the result of the tax bill that cut the corporate tax rates, giving companies cash to invest. Here’s a look.
Since the Shire-Takeda deal is still up in the air, note that Shire sold its oncology business to France’s Servier for $2.4 billion in April, shortly after the announcement that Takeda was bidding for Shire. The Servier deal had been in the works since the beginning of the year and didn’t have a connection to the Takeda bid.
Likely the biggest deals this year have been by Paris-based Sanofi. In late-January, Sanofi acquired Waltham, Massachusetts-based Bioverativ for about $11.6 billion. Bioverativ was a spinoff by Biogen. About a week later, Sanofi bought Ghent, Belgium-based Ablynx for $4.8 billion. Then, on April 17, Sanofi agreed to sell its generics division, Zentiva, to Advent International for about $2.4 billion. Advent is a private equity firm.
Another prominent deal was Celgene Corporation’s acquisition of Juno Therapeutics in January for about $9 billion. This deal came shortly after Celgene’s deal for Impact Biomedicines for $1.1 billion upfront and $1.25 billion in various milestone payments.
In late January, Bothell, Washington-based Seattle Genetics announced a deal to buy Seattle-based Cascadian Therapeutics for about $614 million. It paid $10 per share and picked up Cascadian’s tucatinib, which has a lot of potential for the treatment of breast, colorectal, ovarian and gastric cancers.
In March, GlaxoSmithKline agreed to buy out its stake in its Novartis joint venture for $13 billion. The joint venture was formed in 2014 between the two companies, and offered many of their best-known brands under one company, including Exedrin for pain, NiQuitin for smoking, and TheraFlu for cold and flu. In April, Novartis planned a merger with AveXis for about $8.7 billion.
In the areas of big consumer health business deals, also in April, P&G agreed to buy the consumer health business of Merck KGaA, in Darmstadt, Germany, for about $4.1 billion. In a related story, Pfizer Inc. hasn’t been able to sell off its consumer health division, despite nibbles by GlaxoSmithKline and Reckitt Benckiser Group. Pfizer recently indicated it planned to make a decision about the unit by the end of the year.
In April, Alexion Pharmaceuticals, based in New Haven, Connecticut, announced plans to acquire Swedish company Wilson Therapeutics for about $855 million.
Also in April, Roche completed its acquisition of Flatiron Health, an oncology-specific digital health company for about $1.9 billion. The same month, Roche bought Inception’s Inception 5 program, which focused on regenerative therapies for multiple sclerosis.
Most recently, Janssen Biotech, a subsidiary of Johnson & Johnson’s Janssen Pharmaceuticals,announced on May 2 that it was buying Rockville, Maryland-based BeneVir Biopharma, a subsidiary of HC2, in a deal that could hit more than $1 billion. On March 16, J&J announced it was selling its LifeScan business to Platinum Equity, a private investment firm, for $2.1 billion.
Too many cancer drugs? Crowded market gives investors pause
In London’s world-famous Great Ormond Street children’s hospital, Dr. Karin Straathof is excited about a new cell-based medicine that offers hope for toddlers with incurable nerve tissue cancer.
Her progress with a handful of children for whom standard care does not work reveals the promise of modern cancer drugs, an increasingly crowded pharmaceuticals field from which investors must try to select future winners.
The new therapy using engineered white blood cells has shown anti-tumor activity in the hardest to treat neuroblastoma patients.
“The beauty is that it is very specific in targeting the cancer cells, while leaving healthy tissue unharmed,” Straathof told Reuters, after presenting her early findings at a science meeting in Chicago in April. “It’s an important step forward.”
Autolus – the small British biotech company developing the chimeric antigen receptor T-cell or CAR-T treatment – is equally excited, and is planning a potential IPO on Nasdaq.
But Autolus is far from alone in pursuing CAR-T therapy. In fact, CAR-T treatment – part of the wider field of cancer immunotherapy – is one of the hottest areas of drug research today, with multiple firms piling in.
The biotech dollars are flooding in not only in Europe and the United States but also in China which, with 162 clinical trials, now boasts more CAR-T studies than the United States, according to a Reuters analysis of the latest data.
With over 2,000 drugs in the cancer immunotherapy space, the competitive landscape has never been more crowded as each firm seeks its own proprietary version of often similar drugs.
Overall, researchers are working on more than 5,200 cancer drugs, up 7.6 percent from a year ago, according to the Pharmaprojects database. The sheer number is stretching the ability of scientists to find enough patients to test them on.
Cancer now makes up 34.1 percent of the total drug industry pipeline, up from 26.8 percent in 2010, as companies divert resources into a promising sector where new treatments can often fetch more than $100,000 a year.
‘MORE CIRCUMSPECT’
With the first two CAR-T treatments from Novartis (NOVN.S) and Gilead Sciences (GILD.O) winning U.S. approval last year for rare blood cancers, the promise of such smart medicine is real and life-changing – especially if it can be made to work in solid tumors, as Straathof’s work suggests is possible.
However, the wholesale rush by pharmaceutical and biotech companies into the cancer area poses a dilemma for investors.
A flood of similar products makes it hard for investors to pick those companies that will achieve commercial success.
“More competition means you should be more circumspect,” said Nooman Haque, head of life sciences at Silicon Valley Bank in London, which provides financing for start-ups and venture capitalists.
“The traditional investment thesis in biotech is to have a differentiated medicine with not many competitors, which helps drive value. Here the problem is that even if there is a big patient benefit, there are questions as to how long your advantage lasts and what your commercial edge will be.”
Pharmaceutical executives are not blind to the issue, although each hopes to find a winning formula in immunotherapy – the fastest-growing part of the $100 billion-a-year cancer drug market, with sales expected to top $25 billion by 2021, according to analyst forecasts compiled by Thomson Reuters.
Roche (ROG.S) CEO Severin Schwan, head of the world’s top cancer company, says he expects “an enormous drop-out”, while Sanofi’s (SASY.PA) outgoing research head Elias Zerhouni warned analysts last week that duplication of effort would shrink the time available for drugmakers to recoup their R&D investments.
“The cycle of innovation has been shortened significantly,” agrees Aiman Shalabi, chief medical officer at the non-profit Cancer Research Institute. “There is no doubt we are seeing fast follow-on and many identical agents hitting the same targets.”
The good news for society is that patients will find out much faster than in the past if new approaches work. But that means doctors can rapidly switch to alternatives, leading to increased product churn and uncertainty over future sales.
COMBINATION STUDIES
Twenty years ago, when Roche launched its state-of-the-art cancer drugs Herceptin and Rituxan, it enjoyed years without rivals. Today, there are multiple versions of new drugs targeting molecular pathways with acronyms such as PD-1/L1, PARP and CDK, as well as CAR-T.
Novartis AG76.4
NOVN.SVIRT-X LEVEL 1
—(–%)
“You’re either first or you’re best or you’re nowhere because it has become such a race,” said Paul Major, an investment manager at BB Healthcare Trust (BBH.L), who is cautious about investing in cancer immunotherapy.
Lydia Haueter at Pictet Asset Management is also wary, pointing out there are already five PD-1/L1 drugs on the market – from Merck (MRK.N), Bristol-Myers Squibb (BMY.N), Roche, AstraZeneca (AZN.L) and Pfizer (PFE.N) – and more are coming.
“It seems everybody has a PD-1, so we especially don’t go for those kind of cancer companies,” she said.
Some drugmakers like GlaxoSmithKline (GSK.L) and Novartis that missed the initial PD-1/L1 wave are trying to make a virtue of looking ahead to the next phase of cancer immunotherapy, particularly drug combinations.
Yet last month’s failure of a combination study using a next-generation drug from Incyte (INCY.O) with Merck’s PD-1 Keytruda shows that adding a new agent is no slam dunk for expanding the reach of immune-boosting medicine.
At Great Ormond Street, Straathof is less concerned about doubling up on research and more focused on getting effective, affordable cures – and she hopes automated processes will eventually bring down today’s sky-high drug prices.
“I’m not too worried about duplication. It’s important to not ask the same question in two trials but I think there are a lot of questions to be addressed because there is a lot of nuance in the system.”
Ascension forges first-ever global supply chain company to reduce costs
Ascension is partnering with a large Australia-based international hospital company to form what appears to be the first-ever global supply chain firm.
A major goal of the joint venture between Ascension and Sydney-based Ramsay Health Care, announced Tuesday, is to reduce costs at Ascension’s 151 U.S. hospitals and hundreds of other not-for-profit facilities to the levels in lower-cost countries.
“We believe our providers, and any providers, want products at high quality and lower cost,” Ascension CEO Anthony Tersigni said in an interview. “This gives us visibility into product offerings around the world, and patients will benefit from this greater awareness.”
The joint venture is part of Ascension’s new strategic direction, announced in March, that includes downsizing hospital operations and expanding ancillary businesses such as group purchasing.
Until now, there have been no meaningful efforts to rationalize the healthcare supply chain internationally, even though that’s been done in other industries. Much higher prices for drugs and other products in the U.S. are a major contributor to much higher healthcare spending here compared with other advanced countries.
Rob Austin, director of healthcare consulting at Navigant, said the deal could help reduce U.S. healthcare costs if it helps Ascension learn how much other countries pay for medical products, and it uses that knowledge to negotiate lower prices for U.S. providers.
“Especially with pharmaceutical drugs, if they could get the pricing, that would really make an impact on bending the cost curve,” he said.
But Austin cautioned that it won’t be easy for the new buying group to navigate the differing regulations in each country, particularly when it comes to drugs and medical devices.
The deal, finalized on Tuesday, will be owned equally by Ascension and Ramsay, a for-profit company founded in 1964. Ramsay owns 230 hospitals and outpatient surgery centers in six countries—Australia, France, Indonesia, Italy, Malaysia and the United Kingdom. It’s the largest private hospital operator in Australia and France. It reported revenue of about $6.5 billion (in U.S. dollars) last year, with a net profit of $451.5 million.
Ascension reported $552.7 million in operating income on net operating revenue of $22.6 billion in 2017, down 27% from $753.2 million in operating income on revenue of $21.9 billion in 2016.
In a written release, Ramsay CEO Craig McNally said the new global buying group will seek products internationally that deliver a high level of service and clinical outcomes. This partnership “will allow us to share learnings, best practices and industry knowledge to seek improved quality and outcomes whilst also reducing costs,” he said.
Ramsay’s share price dropped 4% Monday on news that McNally sold 75,000 shares of his company last week for about $4.8 million. The company said McNally sold his shares primarily to meet personal income tax obligations, The Motley Foolreported.
Through the joint venture, Ascension initially will seek out global sources mainly for medical-surgical products such as gowns, sutures and mattresses. It may also source some pharmaceutical products, most likely generic drugs. Later, the buying group may move into medical devices, implants and a broader range of drugs—all of which would face much tougher regulatory hurdles.
Tersigni said he wants the joint venture to extend Ascension’s reach domestically and internationally, strengthen Catholic healthcare, and help his organization gain insight into clinical research around the world.
“Vendors will benefit from having a single point of negotiation to an international platform like ours and streamline discussions between them and health systems,” he said.
Ascension will benefit from Ramsay’s experience in buying products to meet the needs of providers and patients in different countries. For instance, in some Asian countries, people are smaller in stature and require smaller scrubs. In addition, each type of hospital staffer may wear a different color scrub. In the U.K., hospital basins and bedpans are made of disposable cardboard rather than plastic.
Ramsay could gain insights from the operating model of Ascension’s group buying division, called the Resource Group. It focuses on streamlining the purchasing process to reduce vendor costs and thus enable them to offer lower prices without sacrificing profit.
The Resource Group manages a portfolio of $7.7 billion in annual spending for supplies, purchased services, pharmacy, construction materials, capital and IT, and it claims to save participants $1 billion annually.
It plans to channel about $143 million in spending through the new buying group in the first year.
Hospitals around the world buy the same types of products but pay sharply different prices in different countries. “If the new buying group shares any of that comparative pricing, that will be really eye-opening,” Navigant’s Austin said. “Imagine price transparency around the globe. That will call suppliers on the carpet for pricing much more aggressively in the U.S. than in other places.”
Grand Canyon reports Q1 EPS $1.52, consensus $1.39
Reports Q1 revenue $275.7M, consensus $274.13M. End-of-period enrollment increased 9.6% to 91,378 at March 31, 2018, from 83,352 at March 31, 2017, as ground enrollment increased 9.6% to 17,386 at March 31, 2018, from 15,857 at March 31, 2017 and online enrollment increased 9.6% to 73,992 at March 31, 2018, from 67,495 at March 31, 2017
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