Vertex spars with UK’s May over cystic fibrosis med pricing

• Vertex is reaching high in its attempt to get U.K. reimbursement for its cystic fibrosis medications by writing to request “urgent intervention” from Prime Minister Theresa May, citing it as “a test case for the Government’s delivery of accelerated access to innovative medicines in the U.K.”
• The letter contends Vertex made what the company describes as “the most innovative and best offer in the world to NHS England,” but that the NHS did not accept the offer.
• Vertex has its international HQ in London and an R&D site near Oxford. The letter suggests Vertex’s future in the U.K. could be in question, referring to the company “questioning this ecosystem” and that “any future biotech investment in the U.K. is at significant risk.”

Vertex’s cystic fibrosis sales are climbing, with the franchise up 33% year-on-year in the first quarter of 2018. Still there are concerns that the price for Orkambi (lumacaftor and ivacaftor) is too high. In the U.S., the price tag for Orkambi is about $272,000 a year, and a May 2017 report from the Institute for Clinical and Economic Review said that would have to come down more than 70% to be affordable. Vertex shot back a letter to the ICER, accusing the review process of being a “sham” and the body being reliant on “flawed scientific methodology.”

Orkambi was approved in Europe in November 2015. However, in July 2016, the National Institute for Health and Care Excellence stated that Orkambi was “not recommended, within its marketing authorisation, for treating cystic fibrosis in people 12 years and older who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.”

Vertex and the NHS have been in discussions over the subsequent two years to work out a pricing scheme that will cover Orkambi and Vertex’s other two CF therapeutics, Kalydeco (ivacaftor), and tezacaftor/ivacaftor, as well as other future medicines still in development, and use of the medicines in children. In the House of Commons on May 16, May said she wanted to see a quick resolution to the negotiations.

There is a petition ongoing in the U.K., asking the government “to call for a resolution to ongoing negotiations between Vertex Pharmaceuticals, NHS England and NICE as a matter of the utmost urgency.”

The company met with the NHS last Wednesday, but the two sides failed to reach agreement and each issued combative statements.

Vertex accused NHS England of “placing a lower value on the life of a CF patient than other countries around the world,” and called on to the government to intervene.

The NHS response to the meeting, which had an equally battling tone, supported NICE’s decision: “NICE has been clear that Vertex’s pricing is unsupportable. If Vertex really believe they are offering a reasonable deal they should waive their confidentiality clause and let patients and taxpayers judge whether it is fair.”

The next step was Vertex’s letter from CEO Jeff Leiden to May requesting her urgent intervention.

“We are confident our proposal to NHS England would achieve rapid patient access, budget certainty for the NHS, and fair reward for innovation… We respectfully request, therefore, that you urge NHS England to properly value and realise the potential of our portfolio of cystic fibrosis medicines. It would be disappointing in the extreme that, as the NHS turns 70, it is found to be shutting the door to a new era of precision medicines that stand to revolutionize healthcare.”

https://bit.ly/2NE6SkK

KemPharm pushes ADHD filling to 2019

• KemPharm on Monday announced results from a pivotal trial of its attention-deficit/hyperactivity disorder drug KP415 in children ages six through 12.
• The classroom-style, 150-patient study measured efficacy using both the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP) and the Permanent Product Measure of Performance (PERMP) scale. SKAMP is a rating of classroom behaviors in children with ADHD and PERMP is a math test designed to asses a child’s ability to initiate, self-monitor and complete the test.
• The company intends to submit a New Drug Application for the ADHD prodrug in the first quarter of 2019. Previously, KemPharm had been shooting for filing by the end of 2018.

KP415 is an extended release form of d-methylphenidate that uses the company’s ligand activated therapy platform technology. Prodrugs are pharmacologically inactive drugs that become active after being metabolized in the body. KemPharm has claimed the formulation may have lower abuse potential and less variable drug delivery. Its platform strategy is based on turning already approved therapies into prodrugs.

The pivotal study was meant to test both early onset of action and extended duration of therapy. The study showed that KP415 had a statistically significant mean difference in the primary endpoint of SKAMP-combined score change from baseline from one hour to 10 hours compared with placebo.

Depending on what baseline the company used to measure scores — either pre-dose Visit Five or pre-dose Visit Six — the timing of onset of action and length of therapy duration changed. This could be why KemPharm’s stock was off, trading down about 4% in morning trading after shooting higher pre-market.

The Iowa-based biotech intends to collect further clinical data over the course of 2018 ahead of a 2019 NDA submission.

https://bit.ly/2u6zuep

Are your prescriptions contributing to depression?

Hello. I’m Dr Charles Vega, and I am a clinical professor of family medicine at the University of California at Irvine. Welcome to Medscape Morning Report, our 1-minute news story for primary care.

Depression is one of the most common chronic illnesses affecting adults, but can physicians be contributing to the prevalence of depression? An analysis of prescribing habits suggests that the answer is yes.

A new analysis of data from the National Health and Nutrition Examination Survey concluded that more than one third of US adults used a prescription medication that had depression as a potential adverse effect in the previous 30 days.

Concomitant use of three or more of these drugs occurred in almost 10% of adults. And use of meds causing potential suicidal symptoms also increased, with almost a quarter of adults using one of these agents.

Commonly used medications with this adverse effect include beta-blockers, proton pump inhibitors, analgesics, and hormonal contraceptives. The number of medications associated with depression as an adverse event was correlated with a higher prevalence of depression.

This study serves as a reminder that we should all be considering the potential risk for depression when we write routine prescriptions.

https://wb.md/2KUP1HI

Leg Amputations Declined Among End Stage Renal Disease Patients

The rate of lower extremity amputations dropped by more than half in patients with end-stage renal disease (ESRD) on dialysis during a recent 15-year period, according to an analysis of a large U.S. database.

In 2000, the adjusted rate of lower extremity amputations in this patient population was 5.42 per 100 person-years (95% CI 5.28-5.56). In 2014, that rate dropped to 2.66 per 100 person-years (95% CI 2.59-2.72), for a decrease of 51%, said Tara Chang, MD, of Stanford University in Palo Alto, Calif., and colleagues.

The rate of above-knee amputations decreased by 65%, compared with 58.5% for below-knee amputations and just 26% for below-ankle amputations, Chang’s group reported online in JAMA Internal Medicine.

One-year mortality rates after lower extremity amputation also decreased in ESRD patients on dialysis but remained high. In 2000, the rate was 52.2%, and that fell to 43.6% in 2014, the study found.

“This decrease in the amputation rate among patients with ESRD contrasts with the 69% increase in the amputation rate observed from 1991 to 1994 and mirrors the decreasing trend in amputations, which was also driven by a decrease in major amputations reported for the general Medicare population from 1996 to 2011,” Chang’s group wrote.

“The reasons for the declining amputation rate cannot be directly gleaned from our observational analysis. We postulate that one factor may be more aggressive cardiovascular risk factor management, given the declining prevalence of coronary artery disease and of recognized PAD [peripheral arterial disease] observed during the study period.” In addition, improvements in foot care among patients with diabetes could be another potential factor, the researchers said, citing a study that found monthly foot checks were associated with a 17% decrease in amputation rates.

“Although the large decrease in rates of lower extremity amputation among patients with ESRD is encouraging, absolute amputation rates remained high when compared with reported rates in the general Medicare population.” For example, in 2011, the rate was more than 20-fold higher among patients with ESRD compared with the general non-ESRD Medicare population (2.88 versus 0.12 per 100 person-years), the study found.

Study Details

Chang et al analyzed data from the U.S. Renal Data System on all Medicare patients initiating dialysis from 2000 to 2015 — more than three million patients in all. Their mean age was 63; more than half were white (58% in 2000 and 57% in 2014), and less than half were women (48% in 2000 and 44% in 2014). The primary outcome was the number of lower extremity amputations per 100 person years for each year, identified using the International Classification of Diseases, Ninth Edition (ICD-9) procedure codes and Current Procedural Terminology, 4th Revision (CPT-4) codes. The secondary outcome was 1-year mortality rates post amputation.

The investigators calculated amputation rates for each year, using the first year, 2000, as a reference and adjusting for multiple factors including age, race, ethnicity, employment status, Medicaid dual eligibility, cause of ESRD, dialysis modality, dialysis vintage, cardiovascular disease, cerebrovascular disease, PAD, hypertension, diabetes, and smoking.

Amputation rates among ESRD patients with diabetes also decreased by more than half, but remained more than five times higher than for those without diabetes during the study period. For example, in 2014, the rate among patients with diabetes was 4.09 per 100 person years (95% CI 3.99-4.19) compared with 0.74 (95% CI 0.69-0.79) for those without diabetes.

Rates were also higher among men than women. In 2014, the rate for men was 3.01 per 100 person years (95% CI 2.92-3.10) compared with 2.21 (95% CI 2.13-2.30) for women. “These results are consistent with previous studies showing that diabetes and male sex are significant risk factors for amputation in the non-ESRD population,” Chang’s group said.

An analysis by hospital referral regions found that amputation rates tended to be higher in the South and Northeast regions of the United States compared with the West and Midwest. “The persistent regional variation could stem from differences not captured in our analysis, such as in intensity of vascular care, differences in surgical practice patterns, uncaptured socioeconomic variables, or structural differences in the healthcare system management of PAD or diabetes.”

The study was limited to patients who had Medicare parts A and B as the primary payer, and the results might not be generalizable to patients with private insurance, the authors noted. Nevertheless, they said, the analysis highlights the need for more research on ways to prevent lower extremity amputations in this high-risk population.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Stanford Cardiovascular Institute.

Chang reported financial relationships with Janssen, Novo Nordisk, and Fresenius Medical Care; other co-authors also reported relationships with pharmaceutical companies.

• Reviewed by F. Perry Wilson, MD, MSCEAssistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

LAST UPDATED 07.09.2018

• Primary Source

  JAMA Internal Medicine

  Source Reference: Franz D, et al “Trends in rates of lower extremity amputation among patients with end-stage renal disease who receive dialysis” JAMA Internal Medicine 2018; DOI: 10.1001/jamainternmed.2018.2436

https://bit.ly/2N0S52f

Germs grow on medical implants; can they make you sick?

Bacteria and fungi grow on medical implants, such as hip and knee replacements, pacemakers and screws used to fix broken bones, researchers report.

In a new study, Danish investigators examined 106 implants of different types and the surrounding tissue in patients. The findings showed that 70 percent of the implants had been colonized by bacteria, fungi or both.

However, none of the patients with bacteria or fungi on implants showed signs of infection, according to the team at the University of Copenhagen, Denmark.

“This opens up a brand new field and understanding of the interplay between the body and bacteria and microbiomes,” said study co-author Thomas Bjarnsholt, a professor in the university’s immunology and microbiology department.

“We have always believed implants to be completely sterile. It is easy to imagine, though, that when you insert a foreign body into the body, you create a new niche, a new habitat for bacteria,” he explained in a university news release.

“Now the question is whether this is beneficial, like the rest of our microbiome, whether they are precursors to infection or whether it is insignificant,” Bjarnsholt said.

None of the discovered bacteria or fungi were dangerous, the researchers said.

According to study co-author Tim Holm Jakobsen, “It is important to stress that we have found no direct pathogens, which normally cause infection. Of course if they had been present, we would also have found an infection.” Jakobsen is an assistant professor of immunology and microbiology.

“The study shows a prevalence of bacteria in places where we do not expect to find any. And they manage to remain there for a very long time probably without affecting the patient negatively,” he added.

“In general, you can say that when something is implanted in the body it simply increases the likelihood of bacteria development and the creation of a new environment,” Jakobsen said.

The study was published online July 2 in the journal APMIS.

More information

The U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases has more on joint replacements.

https://bit.ly/2L1o3ec

MabVax Secures $11M from Boehringer Ingelheim for Antibody Development

Shares of MabVax Therapeutics have more than doubled this morning after Boehringer Ingelheim inked a deal to acquire the rights to an antibody development program that will be used to target multiple solid tumors.

Under terms of the deal, Boehringer Ingelheim will pay MabVax $11 million in upfront money for the preclinical product. The preclinical asset sold to Germany-based Boehringer Ingelheim targets a glycan commonly overexpressed on multiple solid tumor cancers, MabVax said in its announcement. Additional funds could head to the San Diego-based company from downstream milestone payments. The news was pleasing to investors who snapped up shares of MabVax this morning. The stock has jumped more than 300 percent from Friday’s close of 59 cents per share to a morning high of $2.46 per share.

The stock though is shooting up ahead of MabVax’s delisting from the Nasdaq exchange. The company announced on July 2 that it would not attempt to regain compliance with the Nasdaq to remain on the exchange. Trading of the company’s common stock will be suspended at the open of business on Wednesday, July 11. Nasdaq will thereafter take action to formally remove the Company’s securities from listing and registration on Nasdaq, the company said Thursday.

David Hansen, president and chief executive officer of MabVax, said the asset BI acquired is based on the company’s proprietary HuMab technology.

“This agreement with Boehringer Ingelheim recognizes the value of our innovative approach to discovering novel antibodies to diagnose and treat cancer. We have been committed since the founding of the company to discovering and developing unique fully human antibodies to diagnose and treat patients with cancers where there remain significant unmet medical needs.
Hansen said in a statement.

MabVax said the preclinical antibody series that is part of the deal with Boehringer Ingelheim was discovered from biological samples, originally from patients who were vaccinated against their solid tumors with a glycan antigen-containing vaccine. The discovery of fully human antibodies directly from vaccinated cancer patients has potential advantages which include greater specificity and reduced toxicities, the company said. Following the discovery, MabVax said it reported on early preclinical development activities to establish the utility of the program.

MabVax said the deal with Boehringer Ingelheim does not involve its lead HuMab-5B1antibody program, which is in Phase I clinical trials. MabVax’s Phase I antibody, MVT-5873, is a fully human IgG1 monoclonal antibody (mAb) that targets sialyl Lewis A (sLea), an epitope on CA19-9. MVT-5873 is being studied as a potential therapy for pancreatic cancer, as well as other cancers that have CA19-9 positive tumors. CA19-9 plays an important role in tumor adhesion and metastasis, and is a marker of an aggressive cancer phenotype. In April 2017, the company announced preclinical results for MVT-1075 at the American Association of Clinical Research (AACR) annual meeting. The results showed the drug demonstrated marked suppression and regression of tumor growth in xenograft animal models of pancreatic cancer.

https://bit.ly/2KS42dp

Investment Bankers Leave Firms for Roles in Hong Kong Biotech Companies

More and more pharma companies follow the trend of planning initial public offerings on the Hong Kong Stock Exchange. Another trend following this path is the number of prominent investment bankers who have left their firms for biotech companies in the former British colony.

Since December, Bloomberg reported that at least seven “senior bankers and analysts from top-tier securities firms” have left their lofty positions in the financial sector to take roles in biotech companies based in Hong Kong. The shift is a response to a recent rule change regarding the listing of IPOs on the Hong Kong Stock Exchange. The rule change allows companies to IPO even if they are not yet profitable. Several U.S. companies are rumored to be preparing to take advantage of that change. Among those companies are GRAIL, Inc., which secured a whopping $300 million in an oversubscribed Series C financing round led by multiple Chinese investment groups earlier this summer. Other companies that have planned IPOs this year in Hong Kong include Ascletis, which planned on raising $100 million in a Series C round earlier this year. In May Ascletis filed for an IPO on the Hong Kong exchange as it prepares to launch its hepatitis C treatment Danoprevir by September.

The investment bankers and analysts moving into the biotech world are leaving noted companies like Goldman Sachs, Bank of America Corp., Deutsche Bank AG, Citigroup Inc. and Jefferies Group LLC, Bloomberg reported. The latest banker to leave his post is Richard Yeh, a healthcare analyst with Goldman Sachs. He is taking over the role of chief financial officer at CStone Pharmaceuticals, a Chinese immuno-oncology company.

JHL Biotech, which de-listed from the Taiwan Stock Exchange earlier this year, hired two of the seven bankers to bolster its leadership team ahead of a potential Hong Kong IPO, Bloomberg said. Ellis Chu and Lee Henely, both formerly with Bank of America, took positions with JHL in May. JHL plans on seeking a $35 million IPO next year, Bloomberg said.

In an interview with Bloomberg, Chu said he is “getting in on a sector” where he sees “huge potential.”

“Biotech is an industry that’s exploding, yet still in its infancy in China. There are all sorts of tailwinds,” Chu said.

BioSpace has reported on the significant expansion of the biotech industry in China – an expansion that is expected to continue for years to come. IQVIA (formerly QuintilesIMS) data shows China’s pharmaceutical market is expected to grow to between $145 billion and $175 billion by 2022. Last year Lan Huang, the chief executive officer of BeyondSpring, told BioSpacethat China is a well-spring of biotech opportunity. Huang predicted that companies will increasingly make use of China’s clinical resources to lower time and cost in drug development.

https://bit.ly/2KUOhlT