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Monday, May 28, 2018

Patients with low-back pain benefit from early physical therapy


Patients with low-back pain are better off seeing a physical therapist first, according to a study of 150,000 insurance claims.
The study, published in Health Services Research, found that those who saw a physical therapist at the first point of care had an 89 percent lower probability of receiving an opioid prescription, a 28 percent lower probability of having advanced imaging services, and a 15 percent lower probability of an emergency department visit – but a 19 percent higher probability of hospitalization.
The authors noted that a higher probability of hospitalization is not necessarily a bad outcome if physical therapists are appropriately referring patients to specialized care when low back pain does not resolve by addressing potential musculoskeletal causes first.
These patients also had significantly lower out-of-pocket costs.
“Given our findings in light of the national opioid crisis, state policymakers, insurers, and providers may want to review current policies and reduce barriers to early and frequent access to physical therapists as well as to educate patients about the potential benefits of seeing a physical therapist first,” said lead author Dr. Bianca Frogner, associate professor of family medicine and director of the University of Washington Center for Health Workforce Studies.
Frogner said individuals in all 50 states have the right to seek some level of care from a physical therapist without seeking a physician referral, however, many do not take advantage of this option. She said this may be because some insurance companies have further requirements for payment.
About 80 percent of adults experience back pain at some point during their lifetime, according to the National Institutes of Health.
Currently, patients with low-back pain are given painkillers, x rays and, in some cases, told to rest, said Frogner. She said said seeing a physical therapist first and given exercise is a more evidence-based approach.
Using an insurance claims dataset provided by the Health Care Cost Institute, the researchers reviewed five years of data of patients newly diagnosed with low back pain who had received no treatment in the past six months. The claims were based in six states: Washington, Wyoming, Alaska, Montana, Idaho and Oregon.
The research involved the UW School of Medicine in Seattle and The George Washington University in Washington, D.C.
“This study shows the importance of interprofessional collaboration when studying complex problems such as low-back pain. We found important relationships among physical therapy intervention, utilization, and cost of services and the effect on opioid prescriptions,” said Dr. Ken Harwood, lead investigator for The George Washington University.

FDA OKs new uses for Novartis combo for thyroid cancer


The Food and Drug Administration (FDA) approved Tafinlar (dabrafenib) and Mekinist (trametinib), administered together, for the treatment of anaplastic thyroid cancer (ATC) that cannot be removed by surgery or has spread to other parts of the body (metastatic), and has a type of abnormal gene, BRAF V600E (BRAF V600E mutation-positive).
The FDA granted Priority Review and Breakthrough Therapy designation for this indication. Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases, was also granted for this indication.
The FDA granted this approval to Novartis Pharmaceuticals Corporation.
“This is the first FDA-approved treatment for patients with this aggressive form of thyroid cancer, and the third cancer with this specific gene mutation that this drug combination has been approved to treat,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval demonstrates that targeting the same molecular pathway in diverse diseases is an effective way to expedite the development of treatments that may help more patients.”
Thyroid cancer is a disease in which cancer cells form in the tissues of the thyroid gland. Anaplastic thyroid cancer is a rare, aggressive type of thyroid cancer. The National Institutes of Health estimates there will be 53,990 new cases of thyroid cancer and an estimated 2,060 deaths from the disease in the United States in 2018. Anaplastic thyroid cancer accounts for about 1 to 2 percent of all thyroid cancers.
Both Tafinlar and Mekinist are also approved for use, alone or in combination, to treat BRAF V600 mutation-positive metastatic melanoma. Additionally, Tafinlar and Mekinist are approved for use, in combination, to treat BRAF V600E mutation-positive, metastatic non-small cell lung cancer.
The efficacy of Tafinlar and Mekinist in treating ATC was shown in an open-label clinical trial of patients with rare cancers with the BRAF V600E mutation. Data from trials in BRAF V600E mutation-positive, metastatic melanoma or lung cancer and results in other BRAF V600E mutation-positive rare cancers provided confidence in the results seen in patients with ATC. The trial measured the percent of patients with a complete or partial reduction in tumor size (overall response rate). Of 23 evaluable patients, 57 percent experienced a partial response and 4 percent experienced a complete response; in nine (64 percent) of the 14 patients with responses, there were no significant tumor growths for six months or longer.
The side effects of Tafinlar and Mekinist in patients with ATC are consistent with those seen in other cancers when the two drugs are used together. Common side effects include fever (pyrexia), rash, chills, headache, joint pain (arthralgia), cough, fatigue, nausea, vomiting, diarrhea, myalgia (muscle pain), dry skin, decreased appetite, edema, hemorrhage, high blood pressure (hypertension) and difficulty breathing (dyspnea).

bluebird cash, links lend investment edge

Bellicum Pharmaceuticals (NASDAQ:BLCM) and bluebird bio (NASDAQ:BLUE) are both clinical-stage biotechs that are developing cutting-edge therapies to treat cancer and other diseases. But the fortunes of these two biotechs have been very different over the last 12 months. Bellicum stock is down 37% during the period, while Bluebird's share price has soared more than 125%.
What do each of these biotech stocks have to offer investors now? And which is the smarter pick? Here's how Bellicum and Bluebird compare.


The case for Bellicum

With a clinical-stage biotech like Bellicum, the investing thesis for the stock boils down to what the potential is for the company's pipeline candidates. Bellicum's lead candidate is BPX-501, a T-cell therapy that is given to patients after hematopoietic stem cell transplantation (HSCT) from another donor.
Stem cell transplants can be a lifesaver for some patients with blood cancer and other diseases, but they also come with the risk of infections and graft-versus-host disease (GvHD), where donor stem cells attack the patient's cells. BPX-501 includes T-cells that help fight blood disorders but are genetically modified with a "safety switch" that shut down the T-cells if GvHD or other complications occur.
Bellicum is evaluating BPX-501 in a phase 3 clinical study being conducted in Europe with pediatric patients undergoing HSCT. The biotech expects to report data from this study by late 2018 and plans to file for regulatory approval in Europe next year, assuming the results are positive.
In January, the FDA placed a clinical hold on Bellicum's clinical study of BPX-501 in the U.S. This clinical hold came after three cases of abnormal brain function were reported in patients taking BPX-501. However, the FDA lifted the clinical hold in April after Bellicum agreed to implement an amended study protocol for patient monitoring for potential adverse neurological events.
Bellicum's pipeline also includes three other programs. BPX-601 is a chimeric antigen receptor T-cell (CAR-T) therapy targeting solid tumors expressing prostate stem cell antigen (PSCA), which is a cancer antigen expressed in prostate, pancreatic, bladder, esophagus, and gastric cancers. BPX-701 is a T-cell receptor (TCR) therapy for treating several blood diseases. The company also has a CAR-T program targeting CD19, an antigen expressed by B-cells.
All of these other programs, though, are in early-stage clinical studies. For now, Bellicum's fortunes rest largely on BPX-501.
The biotech completed a stock offering in April that raised $69 million before commissions and other expenses. This amount combined with Bellicum's cash stockpile of $88 million at the end of Q1 should allow the company to fund operations through the end of 2019.

The case for Bluebird

How does Bluebird's pipeline stack up against Bellicum's? The biotech's lead candidate is gene therapy LentiGlobin. Bluebird plans to file for European approval of the drug in the second half of this year for treating transfusion-dependent beta-thalassemia, a rare blood disorder.
With LentiGlobin, a functional human beta-globin gene is inserted into a patient's hematopoietic stem cells outside the body. These modified stem cells are then transplanted back into the patient's blood via infusion.
Another promising gene therapy in Bluebird's pipeline is Lenti-D, which is being evaluated in a phase 2/3 clinical study targeting treatment of cerebral adrenoleukodystrophy (CALD), a rare genetic metabolic disorder. Lenti-D works in a similar fashion as LentiGlobin, except instead of the beta-globin gene, a functioning copy of the ABCD1 gene is inserted into stem cells.
Bluebird also claims a couple of promising CAR-T therapies targeting treatment of multiple myeloma -- bb2121 and bb21217. Celgene is partnering with the biotech on both programs. The big biotech exercised its option in March to co-market bb2121 in the U.S. and exclusively market the drug outside of the U.S., pending approval down the road.
Thanks in large part to funds received from Celgene, Bluebird is sitting pretty when it comes to cash. The biotech reported a whopping $1.57 billion in cash, cash equivalents, and marketable securities in its first-quarter update.
 

Better buy

One of these clinical-stage biotechs is closer to potentially winning approval for its lead candidate. This same biotech also has a deeper pipeline. It claims a tight relationship with a much larger partner. And it's loaded with cash.
That biotech, obviously, is Bluebird. However, with a market cap topping $9 billion, there's a lot of growth baked into Bluebird's share price. Bellicum's market cap is less than $340 million. Good news for Bellicum should provide a bigger catalyst than Bluebird would experience.
So which is the better buy? My view is that Bluebird has the edge, even with its steep valuation. I think that LentiGlobin, Lenti-D, and bb2121 have blockbuster sales potential. Bluebird could stumble if it experiences any pipeline setbacks, but I think the stock should be a winner over the long run.
https://bit.ly/2ISDcgY

Lilly’s cancer business loses its chief just as it’s leaning on oncology for growth


Eli Lilly is leaning on oncology as a key pillar for growth going forward, but with news that its president of the business, Sue Mahony, Ph.D., is retiring, the drugmaker will need to find new leadership for the unit.
Sue Mahony (Eli Lilly)
During her 18 years at Lilly, Mahony has ascended the ranks—earning a spot on the executive committee—and helped see the drugmaker through some big changes. She managed the launch of breast cancer med Verzenio last year and the integration of ImClone, picked up in 2008 for $6.5 billion, Lilly said.
She’s also managed the company’s Canadian operations, and worked in development, marketing and management, according to the drugmaker. Mahony led the company’s recent oncology refocus and was previously senior vice president of human resources and diversity. In that role, she helped the company reorganize into business units in 2009.
“We make medicines that help patients with cancer live longer,” Mahony said in a statement. “What a privilege it’s been to wake up each morning with that as my life’s work.”

Lilly said it will look internally and externally for a successor. Mahony’s last day with the drugmaker is Aug. 31.
Along with many other top players in pharma, Lilly has poured big resources into cancer in recent years, hoping success in the field can help drive growth. In a presentation late last year, Eli Lilly CEO David Ricks said recent launches in cancer—Verzenio, Cyramza and Lartruvo—will help drive the company forward, along with diabetes offerings and drugs for autoimmune diseases.
Before joining the company in 2000, Mahony held various commercial roles in Europe at Amgen, Bristol-Myers Squibb and Schering-Plough, according to Lilly.
The leadership transition at Lilly Oncology comes as several important meds at the drugmaker fall off the patent cliff. Blockbuster erectile dysfunction med Cialis is expected to face cheap rivals in September, and ADHD med Strattera is already under generic assault. The company last year announced 3,500 layoffs to save $500 million in annual expenses, with many coming from early retirements.

Array to update on Phase 3 of melanoma trial at ASCO June 4

Array BioPharma Inc. (Nasdaq: ARRY) announced that it will present data from the Phase 3 COLUMBUS trial of encorafenib and binimetinib in advanced BRAF-mutant melanoma in an oral presentation on June 4, 2018, at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.
“Binimetinib and encorafenib is the first targeted therapy to demonstrate over 30 months median overall survival in a Phase 3 trial and we look forward to presenting the results from the COLUMBUS trial at ASCO,” said Ron Squarer, Chief Executive Officer. “With nearly 15 months median progression-free survival and an attractive tolerability profile, these data underscore the potential of this combination to become an important new treatment option for patients with BRAF-mutant advanced, unresectable or metastatic melanoma.”
As previously announced, the most common Grade 3/4 adverse events (AEs) seen in more than 5% of patients were increased gamma-glutamyltransferase (GGT) (9%), increased creatine phosphokinase (7%), and hypertension (6%) in the encorafenib plus binimetinib group.
Oral Presentation:
Title:
Overall Survival in COLUMBUS: A Phase 3 Trial of Encorafenib (ENCO) Plus Binimetinib (BINI) vs Vemurafenib (VEM) or ENCO in BRAF-Mutant Melanoma
Presenter:
Reinhard Dummer, M.D.
Abstract:
Abstract #223875/Publication #9504
Session:
Melanoma/Skin Cancers
Date:
Monday, June 4, 2018
Time:
9:12 a.m. – 9:24 a.m. Central Time (10:12 a.m. – 10:24 a.m. Eastern Time)
Location:
Arie Crown Theater
The abstract can be accessed through the ASCO website, http://abstract.asco.org/, beginning May 16, 2018, at 5:00 p.m. Eastern Time. Following the presentation on June 4, the slides will be available as a PDF on Array’s website at http://www.arraybiopharma.com.
Array will host an encore webcast presentation of the COLUMBUS trial data.
Encore Webcast:
Date:
Monday, June 4, 2018
Time:
11:15 a.m. Central Time (12:15 p.m. Eastern Time)
Toll-Free:
(844) 464-3927
Toll:
(765) 507-2598
Pass Code:
9615719
Webcast, including replay and conference call slides: https://edge.media-server.com/m6/p/8juh6tcn

Regeneron’s Blue Sky R&D: Q&A


When attending the 2018 Annual J.P. Morgan Healthcare Conference (JPM) in San Francisco this past January, Regeneron Pharmaceuticals held one of my favorite breakout sessions. When Len Schleifer, M.D., Ph.D., Regeneron’s founder and CEO, walked into the Georgian room at the Westin St. Francis, he looked at me and said, “This is crazy,” giving me a fist bump as he made it to the stage to field questions for the Regeneron breakout session. He and his colleagues had just presented in the Colonial room across the hall and had to wade through a sea of people in line to attend the luncheon keynote address by Microsoft founder Bill Gates taking place down the hall. The breakout discussion was interesting, though it got even more so when the last question was asked regarding the “blue sky scenario” of the Regeneron Genetics Center (RGC). The question included the word “vision,” for Schleifer wore a knowing smile when stating, “Let’s hear from the visionary himself.” And with that he leaned back in his chair, punting the question over to his colleague George Yancopoulos, M.D., Ph.D., Regeneron’s president and chief scientific officer.
Yancopoulos provided an impassioned response rarely witnessed during JPM. His retort not only served as the inspiration for this blog, but drove my desire to interview the chief scientist for an upcoming feature in Life Science Leader magazine, which we were fortunate to get scheduled. During our conversation, I asked Yancopoulos what Schleifer’s smile was all about. And while there wasn’t enough room to share his response in our print edition, it seemed like a good addition for our exclusive and free-to-access Beyond The Printed Page online section of the magazine. But to read all that the chief scientist had to say, you’ll need a subscription. Please enjoy this latest Beyond The Printed Page Installment.
Why do you think when Len Schleifer was smiling when fielding the “blue-sky scenario” RGC question at JPM? Was it a bit of a brotherly jab at you for being the “visionary?”
There are lots of visionaries at Regeneron, including Len, though nobody’s more visionary than Roy Vagelos [Regeneron Pharmaceutical’s chairman of the board]. But here’s why I believe Len was smiling. For a long time, 30 years basically, Regeneron has been routinely criticized for doing blue-sky research. In fact, people questioning what we were doing actually used the term “blue sky” when disparaging us as a research boutique. “This is what happens when you put a bunch of scientists in charge of a company,” doubters would say. “They do all this interesting science and develop all this interesting technology, but where’s the beef? Where are the medicines coming out?” We, on the other hand, kept saying, “This is where drugs come from (i.e., fundamental science and fundamental technology), and if we do our jobs right by investing the time and money to build all these capabilities, then we will have an evergreen pipeline of drugs flowing out the back end.” With a solid foundation Regeneron won’t have to worry about buying or in-licensing something from the outside, as we are the company on the bleeding edge of science. We believe the technologies and science we are doing today will pay off in the next 10 to 20 years. Len was smiling because we’ve been around long enough and have seen what “blue sky” can lead to, and it’s been some of the most important medicines of our generation. No other company has been able to do what we have done since the most productive days of Genentech or Merck. You can’t find other companies that have repeatedly, in their own labs, gone from ideas and technologies to important medicines like Regeneron. We are working on a whole stream of things in our pipeline around muscle atrophy, new bispecifics for ways of attacking cancer cells, new ways of using immunotherapy, and new medicines for metabolic disorders and liver disease. All are coming from our own capabilities, our own labs, and our own technologies that people disparagingly referred to as blue-sky efforts so many years ago. But we have demonstrated that if done properly, blue-sky research does pay off.
How do you prevent Regeneron from going the way of other once-productive R&D innovation engines that today are much less relevant?
That is something I worry about; that size and success will do us in. I have four children, and I often tell them that they have a handicap when compared to me. I came from a poor immigrant family, and I knew that in order to survive and make it, I had to work 10 times harder than anybody next to me. My children are the beneficiaries of success, and they are going to have to figure out how to deal with that. I tell them, “The biggest enemy of future success is current success.” I think the secret, both for my children and Regeneron, is to not to get away from one’s roots, and that which made you successful. For me it was a drive and a thirst to use science to make a difference. That was my dream, and why I immediately became attracted to Len Schleifer. Because I believed that’s what he really wanted too. The people we attracted to join Regeneron were also like that, and we built an environment to make it a reality. We have to stay true to the notion of using science to make a difference. We have to continue to attract the best and the brightest people who are driven by the power of science. We have to continue to create a synergistic environment where people can do this together. We have to constantly challenge ourselves and stay passionate. This is why I think the metrics are consistent with the fact that we are still on track. Thirty years ago, we were doing “crazy mouse genetics” while people questioned the rationale. But we knew it was the bleeding edge of science. Today we are the world leader in human genetics, and people continue to question the rationale behind efforts like the Regeneron Genetics Center. But RGC is like a biopharma within a biopharma, and the young team that is running it is taking advantage of anything that we can teach and give them to do. They have the same hunger that made Regeneron successful, and we are helping to create a similar enabling environment. I really feel Regeneron is just coming into its prime. Those other companies that were once game changers but are now less relevant? That’s because when they entered their prime, many of the key people who helped build the place on fundamental science and technology were long gone. I believe Regeneron is a unique company in the history of the biopharma business, as it has an almost magical environment that none of us wants to leave. I think we are poised to do bigger, better, and more amazing things. We’re getting the resources and the technologies, we’re delivering, and we’re engaging a whole new set of partners to do it.

EU makes it easier for companies to produce generic medicines for export


The European Commission on Monday proposed to change intellectual property rules to let pharmaceutical companies produce generic drugs for export to countries and regions where they are not under extended patent protection.

Supplementary protection certificates (SPCs) were introduced to expand patents on certain pharmaceuticals to compensate for the long time it takes such products to come to the market.
While these rules were introduced to aid research investments, it appeared that companies were also shifting production of generics for export out of Europe as a result, the Commission said.
While such drugs would still be protected inside the European Union under the new proposal, companies could make generic versions inside Europe for export to countries where no additional patent protection existed.
“Our initiative will help us open a market of 95 billion euros worldwide,” EU Industry Commissioner Elzbieta Bienkowska told a news conference.
“The same kind of tool worked very well in Canada and helped the pharmaceutical industry to grow and to employ people. That was our reference,” she added.
The Commission said the proposal, which still needs to be approved by the European Parliament and member states, could generate some 1 billion euros ($1.2 billion) of net additional sales per year.