Celgene, Accord Healthcare Resolve Revlimid Patent Dispute

Celgene Corp. (CELG) and Accord Healthcare Ltd. have resolved patent claims over Celgene’s leading product, blood-cancer drug Revlimid.

Under the terms of the settlement, Accord has agreed to vacate challenges to Celgene’s patents, Celgene said Thursday in a securities filing. Also, Celgene granted Accord the ability to market a generic version of Revlimid, the drug lenalidomide, for certain conditions as soon as early 2022, before Celgene’s patents and other restrictions in the U.K. and other European countries expire.

Other terms of the settlement weren’t disclosed.

The deal effectively protects Celgene’s Revlimid sales through early 2022. In its annual report filed with the Securities and Exchange Commission in February, Celgene had guided for European protection “through at least 2022.”

Revlimid, the company’s flagship cancer treatment, accounted for more than half of its $13 billion revenue in the most recent year.

This year, Celgene expects Revlimid net sales to reach $9.5 billion, up from $8.19 billion in 2017.

In 2015, Celgene reached a similar settlement with Natco Pharma Ltd., allowing the Indian drug maker to sell a limited amount of the generic version of Revlimid in March 2022.

Accord, one of the fastest-growing generic pharmaceutical companies in the U.K. and Ireland, sued Celgene in the U.K. last year. The matter was slated to go to trial this year.

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Wainwright Unfazed By Zynerba Ending Trial: Drug ‘Wasn’t In Our Numbers’

Zynerba Pharmaceuticals Inc ZYNE 4.58% stock plummeted 17.8 percent at Thursday’s open after the company ended a Phase 1 study for ZYN001, a tetrahydrocannabinol patch. While there were no adverse effects, the drug failed to meet the targeted top-line results.

Shares regained ground steadily over the day, and were down 3.28 percent at the time of publication late in Thursday’s session.

H.C. Wainwright maintained its bullish view of the company and said ZYN001 had never factored into their estimates.

The Rating

H.C. Wainwright analyst Oren Livnat reiterated a Buy rating on Zynerba with a $23 price target.

The Thesis

The drug “wasn’t in our numbers,” Livnat in a Thursday note. “In fact, we view this early-stage ZYN001 termination as a sign of responsible drug development.” (See the analyst’s track record here.)

The analyst’s valuation is entirely based on ZYN002, an orphan-designated transdermal cannabidiol gel for Fragile X syndrome.

The company said it will be focusing its efforts and resources on developing ZYN002.

Zynerba is set to present new short-term and long-term data from its successful open-label “FAB-C” Phase 2 in FXS at the National Fragile X Foundation International Conference on July 12. ZYN002 is expected to enter Phase 3 trials shortly after, with top-line data projected to be available in the second half of 2019.

Livnat’s valuation assumes a 35-percent probability of success in FXS, product launch by 2021 and 30-percent penetration into the FXS population. All this translates to a peak U.S. sales estimate of $700 million.

https://bit.ly/2zevxJt

Ironwood preparation for activist-driven R&D split puts 40 staffers out of work

Ironwood may have avoided sparring with activists by introducing an R&D split-off, but its employees paid the price.

The Massachusetts drugmaker last week pink-slipped 40 workers, or about 6% of its total staff, according to an SEC filing. The layoffs came “in connection with Ironwood’s intent to separate” its R&D unit from its marketed meds and GI business, the company said.

Ironwood didn’t give details about which departments were hit, other than saying it spared its field-based sales force. Approximately 630 full-time employees will remain on the roster after the reduction, which will likely cost between $5 million and $5.5 million to execute and wrap up by year’s end, the company added.

“We’re making strong progress on executing this separation, including the recent identification of employee roles and responsibilities within the two new companies,” a company spokeswoman toldthe Boston Business Journal in a statement.

The drugmaker, which markets GI product Linzess alongside Allergan, unveiled plans for the R&D divorce in May after fielding demands from activist Sarissa Capital. Under the blueprint, Ironwood will keep Linzess and its treatments for gout and abdominal pain, as well as a prospect for gastroesophageal reflux disease. The new company’s pipeline, meanwhile, includes therapies for orphan diseases and products targeting the nitric oxide signaling pathway for blood flow.

And the strategy worked: Shortly thereafter, Sarissa said it would back Ironwood’s board in its current form instead of trying to win a seat for its leader, Carl Icahn protégé Alex Denner. The spin “is a good first step toward creating shareholder value at Ironwood while preserving strategic optionality,” Sarissa said in a statement at the time.

https://bit.ly/2KSNzlK

With brand-new patent, Roche demands royalties on Lilly’s psoriasis drug Taltz

Here’s a patent gambit for you: Roche’s Genentech unit sued Eli Lilly for infringement Tuesday, claiming the Indianapolis drugmaker’s psoriasis drug Taltz steps on one of its patents.

Thing is, Genentech just won that patent this week.

Taltz has been on the market since 2016—long enough to build up to $486 million in U.S. sales last year, despite heavy competition in its field from Novartis’ first-to-market Cosentyx and other newcomers. But Genentech alleges that the drug, which works by inhibiting the immunology pathway IL-17, infringes its own brand-new patent that covers biological drugs that target that specific pathway.

Now that Genentech has that patent, referred to in the lawsuit as the ‘654 patent, it argues Lilly’s “commercial manufacture, use, offer for sale, or sale of Taltz in the United States or importation of Taltz into the United States constitutes an act of infringement” of some patent claims.

An Eli Lilly representative didn’t immediately respond to a request for comment. The lawsuit seeks damages and royalties in lieu of a permanent injunction.

It’s not the first time drugmakers have fought patent disputes over already marketed drugs. Gilead and Merck have litigated for years over hep C patents as Gilead’s Sovaldi and Harvoni raked in billions. Amgen and partners Sanofi and Regeneron have fought over intellectual property in the PCSK9 class of cholesterol drugs, as well.

Genentech’s patent specifies ownership of “humanized monoclonal antibodies that bind to the IL-17A/F heterodimer.” In the new wave of psoriasis drugs, Taltz isn’t the only IL-17A med; Cosentyx works by inhibiting the IL-17A pathway, too. Valeant’s Siliq goes after multiple IL-17 targets, while UCB’s pipeline drug bimekizumab selectively inhibits IL-17 A and IL-17 F, the Belgian pharma says.

Taltz is among a group of new launches Eli Lilly is counting on for growth as its diabetes business continues to face competitive assault. In the first quarter, sales for the drug grew 52% over the same period last year to $146.5 million. But sales were down quarter-over-quarter in the U.S. due to specialty pharmacy buying patterns, the company reported.

Taltz won its original FDA approval in 2016 to treat moderate to severe plaque psoriasis. In 2017, the drug secured a nod in psoriatic arthritis. Eli Lilly also recently presented positive phase 3 data in ankylosing spondylitis.

https://bit.ly/2KBdxyl

Regulus cuts workforce by 60%, pauses Phase 1 study

Regulus Therapeutics announced a strategic update and corporate restructuring. With the goal of extending its cash runway, Regulus has taken the following steps: recruitment activities for the RG-012 clinical program in Alport syndrome have been paused while discussions with Sanofi to potentially restructure the partnership are ongoing; preclinical research efforts will be focused on its Hepatitis B virus programs; and a workforce reduction of approximately 60% is being implemented. These actions are anticipated to yield over $20M of annualized savings, which are intended to extend the company’s cash runway into mid-2019. The company also announced that it has voluntarily paused the Phase 1 multiple ascending dose, or MAD, study for RGLS4326 due to unexpected observations in its 27-week mouse chronic toxicity study, which was designed to support the Phase 2 proof-of-concept study in Autosomal Dominant Polycystic Kidney Disease previously planned to start in mid-2019. The observations in the mouse chronic toxicity study were unexpected, given the favorable safety profile of RGLS4326 in previous non-GLP and GLP toxicity studies at the same or similar doses supporting the Investigational New Drug application and Phase 1 program. In consultation with FDA, the Company has initiated investigative studies and is planning a new 27-week mouse chronic toxicity study with certain changes that are believed to address the unexpected findings. The 40-week non-human primate chronic toxicity study continues with no significant findings to date. Importantly, RGLS4326 has been generally safe and well-tolerated in the Phase 1 single ascending dose and MAD studies to date.

https://bit.ly/2zeFwhY

Prostate cancer ultrasound treatment may be effective as surgery, radiotherapy

Using high energy ultrasound beams to destroy prostate cancer tumours may be as effective as surgery or radiotherapy, but with fewer side effects.

A new study, carried out at six hospitals across the UK, tracked 625 men with prostate cancer who received a type of treatment called high-intensity focused ultrasound (HIFU).

The research, published in the journal European Urology, is the largest ever study of HIFU treatment used to target prostate tumours. The treatment is similar to a ‘lumpectomy’ for other cancers – where doctors remove only tumour cells, leaving as much healthy tissue as possible.

The findings, from a number of institutions including Imperial College London, Imperial College Healthcare Trust and University College London, found that after five years the cancer survival rate from HIFU was 100 per cent. Approximately, 1 in 10 men needed further treatment. The cancer survival rate from surgery and radiotherapy is also 100 per cent at five years.

The research also showed the risk of side effects of HIFU, such as urinary incontinence and erectile dysfunction, were lower than other treatment options, at 2 per cent and 15 per cent respectively.

The study was funded by the Medical Research Council and SonaCare Inc., who manufacture the ultrasound equipment used in the procedure.

Professor Hashim Ahmed, lead author from the department of Surgery and Cancer at Imperial, said: “Although prostate cancer survival rates are now very good, the side effects of surgery or radiotherapy can be life-changing. Some patients are left requiring multiple incontinence pads every day, or with severe erectile dysfunction.”

He added: “We need to now focus on improving the quality of life for these men following treatment. This latest trial of focal HIFU – which is the largest and longest study of the treatment to date – suggests we may be able to tackle the cancer with fewer side effects.”

Prostate cancer is the most common cancer in men in the UK, with around 47,000 cases every year.

Treatments include surgery to remove the gland, or radiotherapy, which uses radiation to the entire prostate.

However, these treatments can cause collateral damage to surrounding sensitive tissues like nerves, muscles, urine passage, bladder and rectum. The prostate is roughly the size of a walnut and sits between the bladder and the penis.

Surgery and radiotherapy to the entire prostate are effective treatments but can lead to long term risk of urinary problems, like incontinence, of between 5-30 per cent. They also carry a risk of erectile dysfunction of between 30-60 per cent. Radiotherapy can also cause rectal problems like bleeding, diarrhoea and discomfort in 5 per cent of patients.

Ultrasound approach

HIFU is a newer treatment, performed under general anaesthetic, which delivers beams of high energy ultrasound directly into the prostate gland, via a probe inserted up the back passage. There are no needles or cuts to skin. This allows a surgeon to precisely target tumour cells within the gland to millimetre accuracy, with less risk of damage to surrounding tissues.

In the new HIFU study, conducted on men with an average age of 65 and whose cancer hadn’t spread, the risk of urine incontinence (defined as requiring pad use) at five years after the treatment was 2 per cent, and the risk of erectile dysfunction 15 per cent. The team say the results include patients with medium to high risk cancer.

The scientists also tracked the number of patients who needed further treatment following HIFU, (such as surgery or radiotherapy), to treat any cancer cells that had returned. They found 10 per cent of patients needed further treatment by five years, which is comparable to number of patients needing further treatment after surgery or radiotherapy (5-15 per cent).

The team add that prostate cancer patients should talk through all possible treatments with their healthcare team, so they can consider their options fully.

Further follow-up trials are needed to track progress of the patients after ten years, as well as trials that directly compare HIFU with surgery and radiotherapy.

Dr. Caroline Moore, Reader in Urology from the UCL Faculty of Medical Sciences said: “The registry based data from over 600 men is very encouraging. We started the HIFU programme at UCLH in 2003, and now principally use it as a focal treatment, where we treat the cancer but not the entire prostate.

This means that men are much more likely to preserve urinary and sexual function, compared to traditional surgery or radiotherapy. Focal treatment is particularly suitable for men who have prostate cancer visible on MRI, which is contained to one area of the prostate.”

Anthony Murland underwent HIFU treatment in November last year at Imperial College Healthcare NHS Trust to treat his prostate cancer. “I first heard of the treatment from a friend, who had the procedure a few months before. My GP hadn’t heard of HIFU, but was very interested, so I ended up educating him about it. He then referred me for the treatment on the NHS” explained the 67-year-old from Suffolk.

“I liked the sound of the treatment as it seemed the least invasive option, with low risk. The treatment was over in a day – I went in first thing in the morning and was out by the evening. I didn’t have any pain, but needed a catheter for five days, which was a bit uncomfortable.

“I’m closely monitored by my GP, and so far the cancer has not returned.”

 Explore further: ‘Virtual tumours’ predict success of tumour-heating sound waves

More information: Stephanie Guillaumier et al. A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating Clinically Significant Nonmetastatic Prostate Cancer, European Urology (2018). DOI: 10.1016/j.eururo.2018.06.006

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Johns Hopkins Hospital in Baltimore evacuated due to possible TB exposure

Two buildings at the Johns Hopkins Hospital in Baltimore, Maryland, were evacuated on Thursday because people may have been exposed to tuberculosis, a hospital spokeswoman said.

A small amount of the tuberculosis bacteria may have been released while being transported between two of the hospital’s cancer research buildings, the spokeswoman, Kim Hoppe, said in an email. Tuberculosis, or TB, is a serious airborne infection.

Both buildings were evacuated, and employees who were in the area when the incident occurred have been isolated and will be evaluated by the Fire Department, Hoppe said.

“So far, all indications are that no other individuals have been exposed; however, the buildings will remain evacuated until cleared by public safety officials,” Hoppe said.

Helicopter footage by a news crew showed about two dozen people standing outside one of the hospital’s buildings, with some dressed in hazmat suits.

A spokeswoman for the fire department did not immediately respond to requests for comment.

Johns Hopkins Hospital is considered one of the top hospitals in the United States.

In 2016, about 10.5 million people became ill around the world with tuberculosis, and 1.7 million were killed by it. A tiny fraction of those infections and deaths were reported in the United States.

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