Alexion price target raised to $154 from $149 at Credit Suisse. Credit Suisse analyst Martin Auster raised his price target for Alexion to $154 from $149 saying the resolution of overhangs on the shares supports upside, namely if a global 1210 switch strategy is viable given Soliris EU IP uncertainty and what will drive long-term growth for Alexion. The analyst expects partial or full resolution of the first overhang as investors recognize that biosimilar risk may largely be limited to the PNH indication, and lackluster competitive C5 data and probable biosimilar pushouts suggest bearish timeline assumptions are low risk, likely allowing ample time to convert the market to 1210 from Soliris. Auster reiterates an Outperform rating on the shares.
Tuesday, June 5, 2018
Tesaro, Genentech in clinical collaboration
TESARO (TSRO) announced that it has entered into a clinical collaboration with Genentech, a member of the Roche Group (RHHBY), to evaluate the combination of the PD-L1 antibody atezolizumab, the MEK inhibitor cobimetinib and TESARO’s PARP inhibitor ZEJULA in patients with platinum-sensitive ovarian cancer. TESARO and Genentech are also working together to evaluate the combination of ZEJULA and atezolizumab in patients with metastatic bladder cancer as a part of MORPHEUS, Roche’s novel cancer immunotherapy development platform. MORPHEUS is a Phase 1b/2 adaptive platform to develop combinations of cancer immunotherapies more rapidly and efficiently. The planned trial will be conducted by Genentech and is expected to begin by the end of 2018. TECENTRIQ and COTELLIC are registered trademarks of Genentech, a member of the Roche Group
Apollo Endosurgery: FDA OKs revised label for intragastric balloon system
Apollo Endosurgery, Inc. (“Apollo”) (Nasdaq: APEN) a global leader in less invasive medical devices for bariatric and gastrointestinal procedures, announced today that the United States Food and Drug Administration (FDA) has approved updates to the ORBERA® Intragastric Balloon System’s U.S. labeling including a new Physician Directions for Use (DFU), Physician Training, and Patient Directions for Use. Apollo, working directly with the Food and Drug Administration, has developed these updates as a means of communicating ORBERA’s most current safety information to both physicians and patients. Today’s Letter to Healthcare Providers issued by the FDA is intended to highlight the updated labeling. The new DFU is available to physicians and patients at http://www.apolloendo.com/patient-labeling-and-dfus/.
Apollo’s last ORBERA labeling update occurred on June 6, 2017 and included information regarding adverse events of acute pancreatitis and spontaneous hyperinflation, which were not seen during the ORBERA United States pivotal study. The newly revised and approved labeling announced today provides updates for these two events and also adds information regarding the risks of gastric and esophageal perforation, aspiration, and death. The table below summarizes the global rate of occurrence for these adverse events as included in the revised DFU (data as of March 31, 2018) and in the previous DFU (data as of March 31, 2017).
Global Rate (asof March 31, 2018)
| |||||||
| Mortality Rate | 0.01% | <0.01% | |||||
| Gastric Perforation | 0.01% | 0.01% | |||||
| Esophageal Perforation | <0.01% | <0.01% | |||||
| Pancreatitis | <0.01% | <0.01% | |||||
| Spontaneous Hyperinflation | 0.04% | 0.07% | |||||
Also included in this DFU update are specific U.S. rates for acute pancreatitis, spontaneous hyperinflation, gastric and esophageal perforation, and aspiration. The newly approved DFU also separately reports a U.S. mortality rate in ORBERA patients of 0.036% (i.e. less than 4 deaths per 10,000 patients) to provide additional awareness to U.S. physicians and patients.
The table below provides mortality rates for procedures performed in gastrointestinal and bariatric medicine as reported in peer-review literature. The mortality rate of a colonoscopy, which is the most common procedure performed in gastrointestinal medicine, is in line with that of ORBERA. It is also important to understand that colonoscopies are generally performed as a screening procedure, while ORBERA is an actual treatment procedure.
| Procedure | Mortality Rate | |||
Colonoscopy
| 0.03% | |||
Laparoscopic Gastric Banding
| 0.08% | |||
Laparoscopic Sleeve Gastrectomy
| 0.20% | |||
Gastric Bypass
| 0.34% | |||
The U.S. Physician Training has also been revised and approved by the FDA. The updated training provides additional guidance on management of ORBERA patients experiencing symptoms suggestive of persistent intolerance (identified as “refractory intolerance” in the revised labeling). While infrequent in occurrence, these patients can develop an intolerance to the balloon potentially caused by a greater than anticipated delay in gastric emptying with gastric distention and retention of food and fluid. These patients may be at greater risk for both perforation and aspiration at the time of balloon removal.
To help physicians recognize the signs and symptoms of persistent intolerance, and appropriately manage these patients, updated training has been developed to provide:
- more detailed descriptions of the symptomology of persistent intolerance,
- methods of assessing these patients and
- updated recommendations for the management of symptoms and removal of the device.
These updates will be incorporated into the patient labeling, physician labeling and physician training. All previously trained physicians will also receive this new training.
”These updates provide important enhancements to our existing labeling and support our continued emphasis on patient safety. Physicians should always monitor patients closely during the entire term of treatment, and patients should be thoroughly instructed on signs or symptoms of potentially life-threatening adverse events,” said Christopher Gostout, MD, Chief Medical Officer at Apollo Endosurgery.
World-wide, four (4) occurrences of death in patients who received the ORBERA Intragastric Balloon have been reported since the FDA’s “Updated Letter to Healthcare Providers” dated August 10, 2017. One (1) of these four (4) reported events occurred in the U.S. since the FDA’s August 2017 update. In analyzing the information available for these four (4) reports, gastric perforation preceded three (3) of the deaths including the U.S. event reported on 1/12/18. The table below provides summary information regarding these reports as well as access to the full MedWatch reports via a direct link to the FDA’s MAUDE database:
| Location | Event Date | Reported Date | Link to FDA MAUDE Data | |||||||||
| United States | 04/24/2016 | 4/2/2018 | ||||||||||
| Great Britain | 11/7/2016 | 1/3/2018 | ||||||||||
| Brazil | 9/10/2017 | 11/29/2017 | ||||||||||
| United States | 01/12/2018 | 2/12/2018 | ||||||||||
In each case, Apollo provided the event report to FDA through the MedWatch system and, per Apollo’s standard procedures, exhausted all efforts to obtain information directly from the treating physicians. In the absence of information that clearly states the ORBERA did not cause or contribute to the adverse event, Apollo’s standard procedure is to report the events through MedWatch.
Monday, June 4, 2018
Surgery Succeeds in PPI-Refractory Heartburn
For patients with heartburn that was truly refractory to proton pump inhibitors (PPIs), laparoscopic Nissen fundoplication was significantly superior to further medical therapy, a randomized trial found.
Among patients who underwent the surgical procedure, 66.7% had improvement in symptoms of 50% or more at 1 year compared with only 28% of those receiving active medical treatment and 11.5% of those given placebo medical therapy (P=0.007 vs active medical treatment and P<0.0001 vs placebo medical therapy), reported Stuart J. Spechler, MD, of the University of Texas Southwestern Medical Center in Dallas.
Some 20% of adults have heartburn, which can interfere significantly with work productivity and health-related quality of life, he said during a presidential plenary session at Digestive Disease Week.
“Proton pump inhibitors are highly effective for healing reflux esophagitis but not so good for heartburn, and only 58% of patients taking PPIs for chronic heartburn are completely satisfied,” Spechler stated. Treatment options for those patients are limited, and in gastrointestinal practices, PPI-refractory gastroesophageal reflux disease (GERD) is the most common reason for a GERD-related referral, he noted.
Patients with PPI-refractory heartburn should undergo a systematic workup to identify patients who might benefit from antireflux therapy, because these are the patients in whom PPIs have normalized acid reflux but reflux events still evoke heartburn. For patients with PPI refractory heartburn that is reflux related, the benefit of further medical therapy is not established, yet PPI therapy often is continued.
Another approach is to use medications such as baclofen that reduce reflux events, or neuromodulators such as tricyclic antidepressants to dull esophageal hypersensitivity, but these agents can have intolerable side effects.
The potential benefit of anti-reflux surgery for these patients also has not been established, especially for those with reflux hypersensitivity. Hypersensitivity to nonacidic reflux is detected by esophageal impedance monitoring, but the utility of that test in selecting patients for anti-reflux surgery is not clear.
A systematic workup in patients with PPI-refractory heartburn should include a careful medical history, endoscopy with esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance and pH monitoring.
To identify the optimal treatment approach for patients with PPI-refractory heartburn, Spechler’s group enrolled 366 patients from 10 Veterans Affairs medical centers. “We hypothesized that antireflux surgery would be superior to medical therapy with PPIs, baclofen, and desipramine among patients identified as having reflux-related heartburn identified by the systematic workup,” he said.
The active medical treatment consisted of omeprazole, 20 mg twice daily, given 30 minutes before breakfast and dinner, plus baclofen titrated up to 20 mg three times daily. For those who did not respond to baclofen, desipramine was given in doses up to 100 mg at bedtime. Placebo medical treatment consisted of active omeprazole, 20 mg twice daily with placebo baclofen and placebo desipramine.
Patients were seen quarterly, and the primary endpoint was an improvement of at least 50% over baseline in the GERD Health-Related Quality of Life score.
A total of 19.1% of patients dropped out of the trial, 15% were excluded for technical reasons, and 11.5% of patients were found to have PPI-responsive disease once they had been instructed on how to properly take the medication. Only 6.3% of patients were found to have non-GERD organic disorders or major motility disorders, and the largest group of patients excluded were the 27% of those who had functional heartburn.
That left 78 patients who were randomized to surgery or medical therapy. Most of these were men, and mean age was 45. No significant differences were seen in the randomized groups in gender, race, or characteristics such as general health, anxiety , or depression.
“The differences at 1 year were dramatic, with laparoscopic fundoplication being significantly different from active medical treatment, and active medical treatment not being significantly different from placebo medical treatment,” he said.
“Careful workup will exclude most patients with PPI-refractory heartburn from surgery, but for appropriate candidates, surgery is significantly superior to medical therapy,” he concluded.
Spechler disclosed relevant relationships with Takeda and Ironwood.
CMS wants insurers to monitor suspicious prescribing of ‘laughing med’
For years, the Centers for Medicare & Medicaid Services has been hearing concerns that laughing drug Nuedexta was being aggressively pushed by maker Avenair Pharmaceuticals and some doctors for questionable use on dementia patients. Now, the CMS is asking insurers to be on alert for that kind of suspicious prescribing pattern and to let the agency know ASAP if it has concerns.
The drug alert, first reported on by CNN, said that CMS is “monitoring the increased utilization of the drug Nuedexta” after allegations of potential use “for non-medically accepted indications.”It reminds Medicare Part D plan sponsors they have a responsibility to ensure that drugs “are only covered when used for a medically-accepted indication.”
Avanir, in a statement, told CNN that it “is committed to the safe, effective use of Nuedexta for the treatment of patients with PBA.” The company claims its promotional materials, are reviewed both internally and by the FDA.
“We take seriously our role in educating patients, caregivers and health care providers about Nuedexta and PBA and we engage with CMS [Centers for Medicare & Medicaid Services] to ensure communications regarding the use of Nuedexta accurately reflect FDA approved labeling.”
The drug, which is one of only two marketed by California-based Avanir Pharmaceuticals, is approved by the FDA for treating pseudobulbar affect disorder (PBA), a neurological condition characterized by sudden outbursts of uncontrollable laughter or crying seemingly unrelated to mood.
Avanir, a unit of Japan’s Otsuka Holdings, has said that many dementia patients suffer from PBA, but regulators are concerned that Medicare may be paying for the drug for unapproved and potentially fraudulent uses.
An investigation by CNN found that sales of Nuedexta grew 400% in four years to reach $300 million in 2016, and that half of the pills Avanir has sold since 2012 have gone to long-term care facilities even though prescribing information acknowledges the drug has not been extensively studied in elderly patients. One study of people with Alzheimer’s, found it seemed to increase the risk of falling.
CNN said it found that doctors often prescribed Nuedexta to dementia patients in nursing homes, citing a PBA diagnosis, when instead it was being prescribed to control unruly behaviors. Some of those heavy prescribers have been paid by Avanir for speaking about the drug.
One California psychiatrist, for example, received $500,000 in cash, travel and meals from Avanir and Otsuka in the three years ending in 2016, CNN’s story alleged.
To head off such uses, the CMS alert suggested insurers put utilization safeguards in place like preapproval reviews. It also invites providers to give the FDA “feedback on any actions you have taken regarding the drug Nuedexta…”
Shuttered, Closed, Halted and Killed: Biopharma Companies End Programs
Biopharmaceutical companies cancel programs all the time. Usually it’s either because of clinical failures—somewhere along the line they’re just not getting positive data, or because of cost-benefit ratios, which is to say, it’s taking longer to get the data they want in a competitive market and throw in the towel because the company’s business analysis finds it wouldn’t be profitable. Sometimes it’s simply a matter of priorities changing—the company acquired or developed assets in one area and just didn’t have the resources to pursue it appropriately.
Here’s a look at some notable programs that have been shuttered so far this year.
- Roche ends its olesoxime for spinal muscular atrophy program. This broke on June 1. Roche had acquired olesoxime from Trophis for $140 million in 2015, but recently abandoned the drug. “We have had many difficulties in developing this molecule for people with SMA,” Roche stated. “These difficulties have focused on the formulation (the actual liquid preparation of olesoxime), the most appropriate dose to be given and requests from Health Authorities (FDA and EMA) to run a new Phase III study.” The company is still committed to developing a drug for SMA, just not olesoxime. It still has RG7916 in development in collaboration with PTC Therapeutics and SMA Foundation.
- Johnson & Johnson’s Janssen ended its trials of atabacestat for Alzheimer’s disease. The company indicated that it was shuttering the program because of safety issues, rather than any question about the drug’s efficacy. Patients in the EARLY Phase IIb/III clinical trial with preclinical Alzheimer’s disease, as well as a Phase II long-term safety trial, had elevated liver enzymes. EARLY launched in 2015 and was scheduled to wrap in 2024.
The company stated that “the benefit-risk ratio is no longer favorable to continue development of atabacestat for people who have late-onset preclinical stage Alzheimer’s disease.”
Despite the setback, the company indicated it “continues to maintain a strong commitment to discovery and developing new treatments for this devastating disease.”
- Prothena Corporation, headquartered in Dublin, Ireland, announced in April it had shuttered its NEOD001 program for AL amyloidosis after the failure of its Phase IIb PRONTO study and Phase III VITAL study. Shares dropped 60 percent in premarket trading at the news.
The Phase IIb trial did not meet its primary or secondary endpoints. Prothena then asked an independent data monitoring committee (DMC) to review the futility of the Phase III VITAL trial. The committee recommended discontinuing the VITAL study. As a result, Prothena executives decided to discontinue all development.
“We are deeply disappointed by this outcome, particularly for patients suffering from this devastating disease,” said Gene Kinney, president and chief executive officer of Prothena, in a statement. “We are surprised by the results from these two placebo-controlled studies and will continue to analyze the resulting data to share insights with our collaborators in the scientific, medical and advocacy communities. We thank all of the patients, their families, caregivers, investigators, study staff and our employees. Their participation in and commitment to these studies are indispensable to advancing our shared goal of improving the lives of patients with amyloidosis.”
- Merck & Co., announced in February it was halting protocol 019, its APECS Phase III clinical trial of verubecestat (MK-8931) in Alzheimer’s disease.
The company indicated that an external Data Monitoring Committee (eDMC) had recommended ending the trial after an interim safety analysis, saying that the likelihood of benefits didn’t outweigh the risks.
“We are disappointed with this outcome, especially given the lack of treatment options for patients suffering from Alzheimer’s disease,” said Roger Perlmutter, president, Merck Research Laboratories, in a statement. “We are grateful to the patients and caregivers who participated in this study, and despite this outcome, Merck remains committed to developing novel therapies for the treatment of Alzheimer’s and other neurodegenerative diseases.”
- As part of its fourth-quarter earnings report in February, Paris-based Sanofi released a pipeline update, showing it plans to halt several mid-stage drug programs.
Sanofi ended a mid-stage program for isatuximab for acute lymphoblastic leukemia, and SAR428926, an anti-LAMP1 ADC for solid tumors. With no explanation, the company ended its next-generation version of Lemtrada, GLD52 (GZ402668) for relapsing multiple sclerosis, and SAR100842, an LPA1 receptor antagonist for systemic sclerosis.
In addition, after a Phase II trial for SAR156597 for idiopathic pulmonary fibrosis was finished, they ended the program. SAR156597 is an IL-4/IL-13 antibody. It also shuttered a late-stage program for a vaccine for Clostridium difficile.
- In January, Pfizer announced it was abandoning research and development into new neuroscience development, including Alzheimer’s and Parkinson’s disease. The company indicated it will continue working on tanezumab, a late-stage drug for pain it is developing with Eli Lilly & Co., as well as Lyrica, for fibromyalgia. It also intends to continue working on developing neurological drugs for rare diseases.
In a statement, Pfizer said, “This was an exercise to re-allocate spend across our portfolio, to focus on those areas where our pipeline, and our scientific expertise, is strongest.”
Tactile Systems’ Valuation Is ‘Getting Stretched,’ BTIG Says In Downgrade
After doubling in value over the past seven months alone, shares of Tactile Systems Technology Inc TCMD 7.08% are trading at a “stretched” valuation despite expectations for continued growth ahead, according to BTIG.
The Analyst
BTIG’s Sean Lavin downgraded Tactile Systems Technology from Buy to Neutral with no assigned price target.
The Thesis
Tactile Systems, a medical technology company that focuses on treatment of chronic diseases at home, should be able to exceed its own 2018 sales guidance growth of 21-23 percent, Lavinsaid in the Monday downgrade note. Investors should expect the company to deliver future earnings beats, but given the company’s momentum, this is already mostly “expected” at the stock’s current price, the analyst said.
Three concerns exist with Tactile Systems, Lavin said:
- The lack of intellectual property protection on key patents including Flexitouch is “not ideal.”
- Pneumatic compression device companies face minimal barriers to entry given the relatively low tech involved.
- A mid-single digit price erosion is expected and is higher than other medical technology peers.
Nevertheless, the company’s fundamentals remains as strong today as it in the past, and the analyst’s downgrade from a bullish stance is strictly due to valuation concerns, he said. The entire medical technology sector is trading above historical multiples, so investors may want to consider a “disciplined” approach to Tactile Systems’ stock, according to BTIG.
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