Brexit affecting supplies of generic drugs, say pharmacists

Brexit is already affecting supply and prices of drugs in UK pharmacies, the BBC has reported.

The BBC’s 5 Live Breakfast reported that pharmacies are stockpiling generic drugs, and prices are fluctuating amid the political uncertainty.

Manufacturers of branded drugs have been stockpiling their products at the request of the government in preparation for a ‘no deal’ scenario since earlier this year.

Government policy is that the manufacturers’ stockpiles will be enough to cover any shortfall should a ‘no deal’ begin to affect the supply of medicines coming into the UK from Europe.

But people in the entire supply chain are now stockpiling, and this is beginning to affect availability, according to the report.

The Pharmaceutical Services Negotiating Committee (PSNC) said the stockpiling is putting pressure on supply and prices already.

Simon Dukes, chief executive of the PSNC, told the programme: “We have supply shortages. They can be for a number of reasons – they can be because of manufacturing problems or transportation issues, or just an increased demand.

“Where you have those supply shortages, concerns around a ‘no deal’ Brexit are likely to exacerbate those ongoing issues.

“We have worked very closely with the Department of Health and Social Care and fully support what they and the Secretary of State are doing to ensure that all patients get their medicines during the course of the next few months.

“What we are seeing anecdotally is that although the Secretary of State has been very clear and issued a letter to industry that six weeks’ supply should be stockpiled by the manufacturers, what we are seeing is that other stockpiling is happening in other parts of the supply chain, and that may well be exacerbating some of the supply issues.”

In the UK pharmacies pay prices for generic drugs according to a tariff agreed by the government and the PSNC, which is designed to prevent pharmacies competing with each other on price to secure supplies.

The pharmacies are then reimbursed in situations where there is ample supply of the product.

Pharmacies can however pay higher prices in situations where supplies are scarce and there is an urgent need to meet patient demand.

The BBC noted that as a result the NHS will have to cover any fluctuations in costs caused by disruption to the supply chain.

https://pharmaphorum.com/news/brexit-affecting-supplies-of-generic-drugs-say-pharmacists/

Huge Increase in Teen E-Cig Use in 2018, Survey Finds

A second major survey confirms that e-cigarette use among teenagers is soaring, following a CDC report in November that said use among high school students had nearly doubled in just one year.

Reported early Monday, findings from the annual Monitoring the Future survey indicated the percentage of high school seniors who reported current vaping increased from 11% in 2017 to 21% this year. The survey tracks national substance use among U.S. adolescents.

This surge represents the largest single year increase in the use of a single monitored substance ever observed, investigators at the University of Michigan’s Institute for Social Research (ISR) said in their report, published online in the New England Journal of Medicine.

Current e-cigarette usage also nearly doubled among 10th graders in 2018, with 16.1% reporting vaping, compared to 8.2% in 2017 (change of 7.9 percentage points, 95% CI 5.6-10.2). And among 8th graders, vaping prevalence increased to 6.1% from 3.5% in 2017 (change of 2.6 points, 95% CI 1.4-3.8).

The 1-year increase translates into approximately 1.3 million additional adolescents who vaped e-cigarettes containing nicotine in 2018, the ISR researchers reported. The survey included 13,850 respondents in 8th, 10th, and 12th grades across the country. Half of the seniors were randomly selected to answer more detailed questions about their vaping and tobacco use habits.

Last month, results from the CDC’s 2018 National Youth Tobacco Survey also showed a huge single-year spike in e-cigarette usage among high school and middle school studentsin 2018.

That nationally representative survey showed a nearly 80% increase in e-cigarette usage among high school students and a 50% increase among middle school students, with 21% of surveyed high school students reporting current vaping.

“The first reports we heard were from the media, with schools sounding the alarm about these products,” the ISR’s Richard Miech, PhD, told MedPage Today. “Then we had the CDC report, which was the first national survey data to document the increase we had been hearing about.

“Now we have these data showing that for 10th to 12th graders this is the largest year-to-year increase for any substance that we have measured in the 43 years of doing this survey. And it is more than double the previous largest single-year increase.”

Miech explained that since 1975, when the Monitoring the Future survey began, the researchers have tracked teen use of dozens of substances. During this time they have reported more than 1,000 individual increases in current (specifically, past 30-day) substance usage.

“Out of these increases, this is the largest one we have ever seen,” he said.

In September, FDA Commissioner Scott Gottlieb blamed the popularity of the e-cigarette brand Juul among adolescents for what he called an “epidemic” of vaping among high school students. The FDA later promised to restrict sales of most types of flavored e-cigarettes in an effort to keep teens from getting hooked on nicotine.

The Monitoring the Future survey did not ask the 9th through 12th graders which brand or type of e-cigarette they used, but Miech said it does appear that Juul use among teens is largely responsible for the unprecedented increase in usage.

“From the media reports that I’ve seen, it’s hard to imagine that it isn’t responsible,” he said.

The percentage of 12th graders who reported current nicotine use increased in 2018, from 23.7% in 2017 to 28.5% in 2018. This increase was due to vaping and not combustible cigarette use.

Cigarette smoking by teens has been declining for two decades, and the decline continued in 2018 among 12th graders. The survey showed no significant decline for 8th and 10th graders, however.

Marijuana vaping did increase in 2018, with 7.5% of 12th graders reported vaping marijuana within the last 30 days in 2018, compared to 4.9% the previous year.

“Vaping is making substantial inroads among adolescents, no matter the substance vaped,” said Miech. “In 2018 we saw substantial increases in vaping across all substances, including nicotine, marijuana, and adolescents who reported vaping ‘just flavoring.’ Factors that make vaping so attractive to youth include its novelty and the easy concealability of the latest vaping devices, which better allows youth to vape without adults knowing about it. If we want to prevent youth from using drugs, including nicotine, vaping will warrant special attention in terms of policy, education campaigns, and prevention programs in the coming years.”

The Monitoring the Future survey is funded by the NIH’s National Insittute on Drug Abuse.

• Primary Source

  New England Journal of Medicine

  Source Reference: Miech R, et al “Adolescent vaping and nicotine use in 2017-2018 – U.S. national estimates” N Engl J Med 2018; DOI: 10.1056/NEJMc1814130.

https://www.medpagetoday.com/primarycare/smoking/76953

Achillion: Positive Interim Data for ACH-4471 Phase 2 Trials; Clinical Update

ACH-4471, First Generation Oral factor D Inhibitor

– Proof of Concept Validated in both PNH as Monotherapy and in Combination w/C5 Inhibitor– Proof of Mechanism Validated in C3G, End of Phase 2 Meeting Targeted for 4Q 2019

ACH-5228, Next Generation Oral factor D Inhibitor
– Data Demonstrate 3x to 4x Greater Potency and Extended Half-life
– Phase 1Multiple Ascending Dose Trial targeted to begin January 2019
– USPTO has Issued Achillion a Patent Covering ACH-5528 Composition of Matter

Achillion to Host Conference Call and Webcast Today at 4:30 p.m. EST
Access to Webcast at www.achillion.com

Achillion Pharmaceuticals, Inc. (Nasdaq: ACHN), a clinical-stage biopharmaceutical company dedicated to transforming the lives of patients and families affected by complement mediated disorders, today reported interim results for the Company’s Phase 2 trials of its first-generation oral factor D inhibitor, ACH-4471, as well as Phase 1 pharmacokinetics and potency data for its next-generation factor D inhibitors, ACH-5228 and ACH-5548.

“These compelling findings underscore the momentum for Achillion and our factor D portfolio as we advance three oral small molecule compounds through clinical development. Our oral factor D inhibitors have the potential to treat patients suffering from alternative pathway mediated diseases,” said Joe Truitt, President and Chief Executive Officer at Achillion. “In C3G, we have completed patient dosing in our 14-day biomarker/dose ranging study and we are currently enrolling patients in our 6 and 12-month PoC trials. We now have 18 clinical sites open globally and plan to open additional sites in 2019. We are also delighted that the FDA has recently agreed to allow adolescents in our trials as C3G is a disease with unmet medical needs that often begins in childhood. Our C3G plan is to enroll up to 20 patients in our 6 and 12-month trials and to present our data to the FDA at an End of Phase 2 meeting in Q4 2019.”

Truitt continued, “The PNH trial data show that factor D inhibition may play an important role in the future treatment paradigm for PNH patients. Our trials have demonstrated a positive impact on patient’s hemoglobin, reticulocyte counts, LDH, FACIT-fatigue scores and reduced blood transfusions both as a monotherapy and in combination with a C5 inhibitor. Our hypothesis has been reinforced that if the alternative pathway is adequately inhibited then patient benefit can be achieved in fundamentally different ways than has been seen with C5 inhibitors. We believe this is an unmet medical need and a market segment we will continue to evaluate. Additionally, based on the Phase 1 pharmacokinetic and potency data, our next generation compounds, ACH-5228 and ACH-5548, allow for higher alternative pathway inhibition along with a reduced dosing frequency. These compounds have the potential to be transformative both for patients and Achillion and to deliver on the promise of alternative pathway inhibition across a wide spectrum of diseases.”

The Company also confirmed today an expected YE 2018 cash and marketable securities balance of approximately $270 million and a projected 2019 cash burn of $80-85 million.

https://www.marketscreener.com/ACHILLION-PHARMACEUTICALS-35614/news/Achillion-Reports-Positive-Interim-Data-for-ACH-4471-Phase-2-Trials-and-Provides-Clinical-Developmen-27765648/

Puma Top Line Results of Phase 3 HER2-Positive Breast Cancer Trial

Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, announced top line results from the Phase III NALA trial of the Company’s lead drug candidate PB272 (neratinib) in patients with HER2-positive metastatic breast cancer who have failed two or more prior lines of HER2-directed treatments (third-line disease) in the setting of metastatic disease. The Phase III NALA trial is a randomized controlled trial of neratinib plus capecitabine versus Tykerb^® (lapatinib) plus capecitabine in patients with third-line HER2-positive metastatic breast cancer. The trial enrolled 621 patients who were randomized (1:1) to receive either neratinib plus capecitabine or lapatinib plus capecitabine. The trial was conducted globally at sites in North America, Europe, Asia-Pacific and South America. The co-primary endpoints of the trial are centrally confirmed progression free survival (PFS) and overall survival (OS). An alpha level of 1% was allocated to the PFS and 4% allocated to OS. The study was to be considered positive if either of the co-primary endpoints was positive. Puma reached agreement with the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the design of the Phase III clinical trial and the European Medicines Agency (EMA) also provided follow-on scientific advice (SA) consistent with that of the FDA regarding the Company’s Phase III trial design and endpoints used in the trial.

For the primary analysis of centrally confirmed PFS, treatment with neratinib plus capecitabine resulted in a statistically significant improvement in centrally confirmed PFS (p=0.0059) compared to treatment with lapatinib plus capecitabine. For the primary analyses of OS, neratinib plus capecitabine resulted in an improvement in OS that did not achieve statistical significance but trended positively in favor of the neratinib plus capecitabine arm of the study (p=0.21). For the secondary endpoint of time to intervention for symptomatic central nervous system disease (also referred to as brain metastases), the results of the trial showed that treatment with neratinib plus capecitabine led to an improvement over the combination of lapatinib plus capecitabine (p=0.043).

The safety profile of neratinib in the Phase III NALA study was consistent with previous clinical trials of neratinib.

Full results of the trial will be submitted to health authorities around the world, including the U.S. Food and Drug Administration and European Medicines Agency. Results of the trial will be submitted for presentation at a major medical conference in 2019.

Alan H. Auerbach, Chief Executive Officer and President of Puma Biotechnology, said, “We are highly encouraged by these results from the NALA trial with the combination of neratinib plus capecitabine in patients with HER2-positive metastatic breast cancer who have failed two or more prior lines of HER2-directed treatments. We look forward to working with the regulatory authorities in the hope of bringing another potential treatment option to patients with HER2-positive metastatic breast cancer as soon as possible.”

Conference Call

Puma Biotechnology will host a conference call at 1:30 p.m. PST/4:30 p.m. EST on Monday, December 17, 2018, to discuss the results of its NALA trial. The call may be accessed by dialing 1-877-709-8150 (domestic) or 1-201-689-8354 (international). Please dial in at least ten minutes in advance and inform the operator that you would like to join the “Puma Biotechnology Conference Call.” A live webcast of the conference call may be accessed on the Investors section of the Puma Biotechnology website at http://www.pumabiotechnology.com. A replay of the call will be available approximately one hour after completion of the call and will be archived on Puma’s website for 30 days.

https://www.marketscreener.com/PUMA-BIOTECHNOLOGY-INC-32676238/news/Puma-Biotechnology-Announces-Top-Line-Results-of-the-Phase-III-NALA-Trial-of-Neratinib-in-Patients-27765674/

Bristol, Boston Med Center to Collaborate on Immuno-Oncology Marker Research

Bristol-Myers Squibb Company (NYSE:BMY), and Boston Medical Center, a private, not-for-profit, academic medical center, today announced a multi-year joint research study to identify and analyze potential sensitivity and resistance markers in patients treated with standard-of-care checkpoint inhibitors. The comprehensive, multi-dimensional study will place an emphasis on uncovering mechanisms associated with lack of response to Immuno-Oncology (I-O) therapies, with the ultimate goal of identifying prognostic and potentially predictive I-O biomarkers in a variety of cancers.

“Our newly opened R&D site in Kendall Square is focused on better understanding, and ultimately overcoming, the challenge of I-O resistance. We are thrilled to establish our first partnership since the site opened with our new neighbor, Boston Medical Center, with the goal of uncovering new insights into the biology of cancer and how it evolves with exposure to I-O intervention,” said Saurabh Saha, M.D., Ph.D., senior vice president and global head of translational medicine, Bristol-Myers Squibb. “The information we glean from this collaboration will ultimately inform the development of novel therapeutic strategies to improve response rates and outcomes for patients.”

Through the study, researchers will explore the role of tissue and circulating biomarkers on treatment sensitivity and resistance. In addition, scientists will investigate the role of the microbiome as a potential predictive biomarker in patients receiving treatment with immune checkpoint inhibitors.

https://www.marketscreener.com/BRISTOL-MYERS-SQUIBB-COMP-11877/news/Bristol-Myers-Squibb-and-Boston-Medical-Center-Announce-Research-Collaboration-to-Investigate-Mark-27765830/

Galapagos NV initiates ISABELA Phase 3 program

Galapagos NV announced that it has dosed its first patient in the worldwide ISABELA Phase 3 program with autotaxin inhibitor GLPG1690 in IPF. “Today’s news again demonstrates our commitment to the rapid advancement of our IPF franchise, including the ISABELA and the PINTA trials. We are excited by the feedback received from participating sites and KOLs, which underscores the need for novel treatments to address the remaining high unmet need in IPF,” said Galapagos Chief Medical Officer Dr. Walid Abi-Saab.
https://thefly.com/landingPageNews.php?id=2838237

EyePoint added to Nasdaq Biotechnology Index

EyePoint Pharmaceuticals (EYPT) announced that it has been selected for addition to the NASDAQ Biotechnology Index (NBI). EyePoint’s addition to the NBI will become effective prior to market open on Monday, December 24, 2018.
https://thefly.com/landingPageNews.php?id=2838241