Market Place
As India deals with new currency
notes and the US elects Donald Trump as its new President, Phispers brings you
the latest pharma news from both these countries. Probe into price collusion in
the US resulted in pharma stocks tumbling in India. There is also news on a likely
breakthrough in the treatment of diabetes, the latest on the vaccine scandal in
China, compliance news from across the globe and more.
Drug
firms in US face probe into price collusion; feel the pressure in pricing
Last week, Senator Bernie Sanders asked the US
Department of Justice and the Federal Trade Commission to investigate three insulin makers for
price collusion. Citing 13 instances since 2009, he said the prices of Lantus
(Sanofi’s
blockbuster diabetes medication) and Levemir
(Lantus' direct competitor, made by Novo Nordisk), “have gone up in tandem in the US”. And from 2014 to 2015, the price of both medications “went up by 29.9 percent”. Sanders’ letter also cites that Eli Lilly and other companies have been fined in Mexico for colluding on insulin
pricing.
The letter has been sent at a time when Andy Slavitt, the acting administrator
for the Centers for Medicare & Medicaid Services (CMS), condemned drug
makers for cost increases.
Total prescription drug spending in 2015 was about US $
457 billion, or 16.7 percent of healthcare spending. Based on recent trends,
Slavitt said CMS is estimating average annual increases of 6.7 percent until
2025.
However, drug makers are already feeling the pricing pressure.
GlaxoSmithKline
CEO Andrew Witty said the company has seen a 2 percent
dip in net prices in the US this year, and expects further reductions driven by
payer and hospital consolidation.
In addition, new data-driven flexible pricing
schemes being offered by Swiss drug-maker Roche and other drug companies are replacing the current “pay-per-pill” approach. These mechanisms are more popular in cancer treatment. Roche has introduced flexible pricing for cancer drugs in about a dozen European countries, including Italy, Belgium, Hungary, Switzerland and Austria.
Indian pharma stocks
crash due to price collusion probes in the US
The probes in the US
are impacting share prices of Indian pharmaceutical companies, which together comprise the
second-biggest suppliers of generic medicines to the US. The share prices of
Indian pharma dipped amid mounting concerns about potential pressures on drug
prices in the US, after news of a Justice Department probe. Prosecutors in the
US are investigating generic pharmaceutical companies for suspected price collusion.
Among the drug makers
to have received subpoenas are companies like Mylan, Teva Pharmaceutical Industries, Actavis (which Teva bought from Allergan Plc in August), Lannett Co, Impax Laboratories, Covis Pharma Holdings Sarl, Sun Pharmaceutical Industries, Mayne Pharma Group, Endo International’s subsidiary Par Pharmaceutical Holdings and Taro Pharmaceutical Industries.
More arrests in
Chinese vaccine scandal case In a crackdown on the black market sale of vaccines, China’s eastern province of Shandong saw 27 additional arrests, taking the total number of people arrested to 324. Nearly US $ 90 million worth of illegal
vaccines are estimated to being sold in dozens of provinces across China. A mother-daughter duo — Pang Hongwei, a former pharmacist at a hospital in Shandong and her 21-year-old daughter — were caught peddling 25 kinds of unrefrigerated vaccines, which could have compromised inoculations and resulted in
paralysis and even death. Probes found 300 illegal distributors aiding Pang
across 24 provinces and regions. The drug regulator in Shandong said it would work with police forces and the health ministry to inspect vaccine stocks to ascertain where US $ 88 million worth of vaccines had ended up. The case – involving vaccines against meningitis, rabies and other illnesses – underlines the challenge being faced by China to regulate its fragmented supply chain.
Fake vaccines scandals have been a
public-health menace in other countries as well. For instance, it was learnt that
substandard products had been distributed across Indonesia since 2003. As a result, the
Indonesian government will reinoculate children
aged 10 and below. A diabetes
breakthrough? Insulin resistance reversed by removal of proteinA team of investigators
led by researchers from the University of California School of Medicine
reportedly reversed diabetic insulin resistance and glucose intolerance in mouse models of obesity and diabetes by removing the protein – galectin-3 (Gal3).When you bind Gal3 to
insulin receptors on cells, the protein prevents the insulin from attaching to the receptors,
resulting in cellular insulin resistance. The researcher showed that by
genetically removing Gal3 or using pharmaceutical inhibitors to target it,
insulin sensitivity and glucose tolerance could be returned to normal, even
among older mice. However, obesity remained unchanged.
“This study puts Gal3 on the map for insulin resistance and diabetes in mouse model,” said senior author of the study. “Our findings suggest that Gal3 inhibition in people could be an effective anti-diabetic approach,” the author added.
Sanofi,
Novartis, GSK do not effectively disclose clinical trial data, finds online
tool
A new
online tool was launched last week by AllTrials, a consortium of researchers and medical journals that has
been pushing the pharmaceutical industry to do a better job of disclosing
clinical trial data.
This
is an important, though a contentious issue because without access to such
data, independent researchers are unable to verify results that can lead to
improved treatments, better healthcare, and lower costs.
For
instance, the tracker found that Sanofi had the largest number of missing trial results – there are 285 missing results from 435 eligible trials, which meant the company has not shared 65 percent of its findings.
Among
other transgressors is Novartis, which did not disclose results
for 201 studies, or nearly 38 percent of 534 eligible trials. And
GlaxoSmithKline failed to release findings for 183 trials, or almost 23 percent
of 809 eligible studies.
Compliance
news: Valeant, Resonance Labs in trouble; Mylan settles dispute with
Strides
FDA’s warning letter for Valeant: There is fresh trouble for Valeant Pharmaceuticals, which has been dealing with
several problems, including a government probe into its accounting and pricing
practices. The US Food and Drug Administration (FDA) has sent a warning letter to Valeant
for its manufacturing problems that reflect an inability to integrate some of
the products that have come into its fold through acquisitions.
The
letter describes how a Valeant production plant in Rochester (New York), which mostly
makes products for the Bausch + Lomb division, experienced various
problems with the OraPharma ONSET Mixing Pen — a compounding and dispensing device used for mixing two solutions together. “Organizational structure has not assured that acquired products are adequately integrated into your quality management system,” the letter said. Valeant acquired OraPharma in 2012.
Compliance trouble for Resonance Labs: Indian API manufacturer Resonance Labs is in compliance trouble as Health Canada
has placed it on its Inspection Tracker, based on information obtained from a
regulatory partner regarding general GMP observations. Usually alerts from
Health Canada are followed by either a warning letter from the FDA or a Non-Compliance
Report from the European authorities.
Mylan and Agila settle dispute over pending payments: Mylan NV’s US $ 1.6 billion cash acquisition of Agila Specialties (a developer, manufacturer and marketer of high-quality generic injectable products) in 2013 from India’s Strides Arcolab had run into compliance
problems. Within a year of acquiring Agila, Mylan had received a notice from the FDA regarding
violations of GMPs. But last week, Mylan settled its two-year old dispute over pending payments
with Strides. Mylan received US $ 170 million as final settlement.
Lupin receives EIR from FDA for Goa plant: In June we had asked how long it would take for Lupin to address FDA’s concerns
pertaining to its Goa facility. And we were positively
surprised this week when Lupin
announced a successful closure of the inspection. Lupin received the Establishment Inspection Report
(EIR) from the US health regulator for its Goa plant leading to closure of all
outstanding inspections of the facility.
Old Ranbaxy facility being inspected by FDA: Next up is Sun Pharmaceuticals, as the US FDA commenced its scheduled inspection of the Mohali manufacturing site of Ranbaxy.
Sun had acquired Ranbaxy two years back as part of a US $ 4 billion deal with
Japanese drug maker Daiichi Sankyo. As per news reports, the inspection started on
November 7, and may continue for a week.
GSK sues Pfizer, as both companies announce plant
closures
Last week, both GlaxoSmithKline and Pfizer made
announcements regarding shutting down manufacturing plants. GSK Consumer
Healthcare announced it will close its manufacturing facility
in Ermington (Australia) in 2020. And US drugs behemoth Pfizer said it will close two manufacturing sites
in the UK by
2020, resulting in 370 job losses. The Park Royal site in London, which Pfizer inherited when it acquired Hospira
in September this year, will shut down by May 2017. The site takes liquid medicines and puts
them into dosed vials, which are then sold to hospitals. The global cold chain packaging and
distribution site in Portsmouth will shut by the end of 2020. The Pfizer
spokesperson said the decision has nothing to do with Brexit. The global
packaging site will be consolidated in Puurs (Belgium), “where there are better production capabilities to support the product pipeline”,
the spokesman added.
Meanwhile, British drug giant, GSK has filed a patent infringement lawsuit against Pfizer over allegedly copying its popular meningococcal group B vaccine – Bexsero. The drug competes with Pfizer’s Trumenba. Meningococcal disease is a
potentially fatal bacterial infection of the bloodstream, brain and the spinal
cord lining. GSK’s
Bexsero is currently the only vaccine against the disease that is available in
most markets. And the legal step taken by GSK represents its desire to protect the drug’s powerful market share.
Biotech startup Cempra’s woes continue
Last week, Wockhardt’s ambitious
turnaround plans received a serious setback when Cempra — a clinical-stage pharma company focused on developing antibiotics — learnt that the US FDA may not allow it to use an active
pharmaceutical ingredient (API) produced by Wockhardt for approval and in the
commercial use of its product Solithromycin.
A regulatory panel of experts on November 4 narrowly recommended that Solithromycin — an antibiotic from Cempra being
projected as an answer to the menace of antibiotic resistance — should be approved for use. The 7-to-6 votes in
favour of Solithromycin suggests that there is an unmet
need for new treatments that outweigh the safety concerns surrounding the
product.
The Wall Street had forecasted
Solithromycin to be a blockbuster. Little wonder then that the investors were
rattled last week and the stock plunged 58 percent after the US FDA disclosed its review.
Impressions: 2829
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#PharmaFlow by PHARMACOMPASS
10 Nov 2016
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FDA uncovers systemic data manipulation in China; India’s pharma lobby rubbishes report on pollution
This week, Phispers brings you news about Wockhardt and how its
turnaround plans are going awry. There is also news about Novo Nordisk ending
development of an oral form of insulin, data manipulation at Beijing Taiyang,
the latest on treatment of high cholesterol and lots more.
Novo ends
development of oral insulin, slashes long term growth forecast
Novo Nordisk – the world’s biggest maker of insulin – slashed its long-term profit-growth forecast by half due to pressure on prices in its largest market – the US. The company is also ending development of an oral form of insulin, which has long been an unattainable dream for the global
pharmaceutical industry.
The Danish pharma company will be relying
more on in-licensing early stage projects and working with external academic
collaborators. Moreover, the company will focus more on diabetes and obesity
adjacent conditions such as nonalcoholic steatohepatitis (NASH), cardiovascular
disease and chronic kidney disease.
In the US, Novo is experiencing payer
difficulties that have resulted in disappointing performance of its modern
insulins. The profit-growth estimate was trimmed to 5 percent from the 10 percent projected in
February this year, as it lost key contracts. The company also saw some
products being excluded from insurance-coverage plans as it promised large
rebates in the US on 2017 prices.
While Novo controls almost half the
global market for insulins, the intermediaries who negotiate prices for insured
patients in the US are opting for cheaper alternatives.
Lower prices and escalating competition
from biosimilars have dimmed prospects for Novo, Sanofi and Eli Lilly & Co.
These pharma companies have been forced to deepen rebates and discounts.
Systemic data
manipulation uncovered at Chinese API manufacturer
The
FDA has issued a warning
letter to Beijing Taiyang Pharmaceutical Industry, a manufacturer of active pharmaceutical ingredients such as diphenyhydramine hydrochloride, a commonly used ingredient in cold preparations.
The warning letter states that FDA investigators “observed systemic data manipulation across the facility.” The investigators documented “unexplained deletions of laboratory test results, discovered that analysts repeated tests until they obtained acceptable results and that the company failed to investigate results that were out-of-specification.”
The
FDA investigators
observed, through a window, a warehouse containing numerous drums bearing the company’s label. “When the investigators
requested access to this warehouse, Beijing Taiyang’s staff barred them from
entering the warehouse to examine the containers,” the letter adds.
The following
day, when FDA investigators were given access to the warehouse, they observed
that a significant number of drums had been removed and were not available for
inspection. The firm also relied on falsified and manipulated test results to
support batch release and stability data.
The FDA had
placed Beijing Taiyang on its import alert list in April of this year.
Wockhardt’s compliance foibles haunt biotech startup Cempra
Wockhardt’s
ambitious turnaround plans received a serious setback last week when Cempra, a
clinical-stage pharmaceutical company focused on developing antibiotics, learnt
that the US Food and Drug Administration (FDA) may not allow it to use an active
pharmaceutical ingredient (API) produced by Wockhardt for approval and in the
commercial use of its product Solithromycin.
Two of Cempra’s products are in advanced clinical development. One of them – Solithromycin – has been successfully evaluated in two Phase 3 clinical trials for community acquired bacterial pneumonia (CABP). Its applications for approval have been accepted by the FDA and the EMA.
The setback to Cempra was the result of an
in-person meeting held with the FDA in late October. The reason for the FDA
decision was an import alert placed on a Wockhardt manufacturing facility in August 2016, several months after Cempra’s New Drug Applications (NDA) with Wockhardt had been submitted and accepted for review by the FDA. Cempra began an active dialog with the FDA to determine if the API produced at Wockhardt prior to the import alert was adequate for the NDA.
While Cempra plans to provide the FDA with data from API sourced from another supplier, the news is a serious setback for Wockhardt’s ambitious turnaround plans to fix its compliance issues and become an antibiotic research powerhouse.
Sanofi-Regeneron’s potential blockbuster runs into manufacturing problems
Last week, Sanofi and Regeneron Pharmaceuticals’ Sarilumab – a product in development for the treatment of moderately to severely active rheumatoid arthritis (RA)—received a setback. The two companies announced that the
US FDA has issued a Complete Response Letter (CRL) regarding the Biologics
License Applications (BLA) for Sarilumab.
The CRL refers to certain deficiencies identified during a routine
good manufacturing practice (GMP) inspection of the Sanofi facility in Le Trait
(France) where Sarilumab is filled and finished. Satisfactory resolution
of these deficiencies is required before the BLA can be approved.
However, Sarilumab performed extremely well in a head-to-head
clinical study against AbbVie’s world best-selling drug, Humira.
The manufacturing glitch was also the only negative in Sanofi’s better than expected earnings report which was released last week in which Sanofi announced that it would exit its European generics business in the next 12 to 24 months.
Cholesterol woes: Raising HDL can’t save you, and new drugs don’t work.
Last year, two new drugs – Rephata and Praluent – that lower cholesterol, came on the market. Back then, analysts had estimated sales of more than US $ 3 billion a year. Working by blocking a protein called PCSK9, the drugs would clear out LDL, or bad cholesterol.
While Sanofi and Regeneron launched Praluent, which is said to succeed where the traditional treatment – an inexpensive class of drugs called statins – fails, Amgen launched Rephata with a similar mechanism of action.
A year on, doctors are reluctant to write prescriptions until they
are sure of the benefits. Similarly, insurers are unwilling to pay for these
drugs.
“These launches so far are close to, if not the biggest, wastes of development and commercial investment in recent industry history,” Geoffrey Porges, a biotech analyst at Leerink, an investment bank specialising in healthcare told STAT News.
There was more bad news for patients suffering from high
cholesterol. A study
published this week has found little evidence that raising HDL, widely known as
good cholesterol, protects against heart attacks and strokes.
The study was published in the Journal
of the American College of Cardiology. The drug industry has repeatedly failed to design a pill that might improve patients’ lives by increasing HDL.
A decade ago, Pfizer spent more than US $ 800 million to get the
HDL-boosting medication torcetrapib into
late-stage trials, only to find that more patients died on the drug than on
placebo. Roche was next to fail when its drug, dalcetrapib, came up
short in a 16,000-patient trial in 2012. And last year, Eli Lilly shut down a
study testing its evacetrapib on 12,000 patients after discovering that the
drug had no effect on heart attack and stroke.
Pfizer fined for violating environmental laws in the US
For the second time in recent years, Pfizer has been fined by the American authorities for violating the
Clean Air Act at a manufacturing plant in Barceloneta, Puerto Rico.
Pfizer
was fined US $ 190,000 for failing to disclose information about hazardous
chemicals that were used at the concerned plant.
In early 2014, the Environmental Protection Agency (EPA) had found that Pfizer stored certain substances — in this case, ammonia and methylamine — that exceeded permitted amounts. This triggered a requirement to file a plan, which Pfizer failed to do and had to be fined. The substances were also used without properly being disclosed to the EPA.
Pharmexcil refutes report on drug-resistant
bacteria
Growing
antimicrobial resistance (AMR) is one of the gravest threats to human health.
Global deaths because of drug-resistant infections are projected to reach 10
million per year by 2050, with cumulative economic losses of US $100 trillion.
A new report by campaigning organisation – Changing Markets – titled ‘Superbugs in the Supply Chain - How pollution from antibiotics factories in India and China is fueling the global rise of drug-resistant infections’ has revealed
the presence of drug-resistant bacteria at pharmaceutical manufacturing sites
in India.
On-the-ground research and analysis of water samples found high levels of drug-resistant bacteria at sites in three Indian cities: Hyderabad, New Delhi and Chennai. Out of 34 sites tested, 16 were found to be harboring bacteria resistant to antibiotics, the report says. At four of the sites, resistance to three major classes of antibiotics was detected, including antibiotics of ‘last resort’, those used to treat infections that fail to respond to all other medicines.
The report says antibiotics manufactured at or near these sites are being exported to United Kingdom’s National Health Service (NHS), French hospitals, and pharma majors including US distribution giant McKesson and French company Sanofi’s generics arm Zentiva.
The report cites
Hyderabad-based Aurobindo Pharma as one of the worst offenders. However, Pharmaceuticals Export Promotion Council of India (Pharmexcil), which is part of India’s ministry of commerce, has termed the report as “fabricated” and “backed by vested interests” to malign the Indian pharma industry—the world’s largest producer of antibiotics.
Aurobindo Pharma’s wholetime director M Madan Mohan Reddy is the chairman of Pharmexcil.
EMA probes Wanbury Pharma; French agency ANSM warns about fake GMP certificates
Mumbai-based
drug manufacturer Wanbury Pharma, which is one of the largest exporters
of diabetes drug metformin, had been served a show-cause notice by the Maharashtra Food and Drug Administration
last week for allegedly re-labelling its drugs that were being exported to
Brazil, Mexico, Bangladesh and Pakistan.
Wanbury has now
come under the lens of the European Medicines Agency (EMA). The EMA is learnt
to be investigating the allegations made by the Maharashtra FDA.
Meanwhile, the
ANSM (French agency for the safety of health products) has been informed of the
use of several falsified GMP certificates under its letterhead for import and export activities of active substances. “Because of a recent increase in observed cases, the ANSM reminds stakeholders that the authenticity of GMP certificates should be checked on EudraGMDP Community database,” the ANSM website says.
Teva
takes a shot at delaying generic Copaxone by writing to FDA
Teva Pharmaceutical has submitted a document to the US FDA explaining
the differences between its original multiple sclerosis drug Copaxone and the generic
product being marketed by Momenta and Sandoz.
In order to enter the
market, the generic version of Copaxone requires both FDA approval and legal
confirmation that it does not violate Teva's patent.
According to analysts,
the document is designed to delay the entry of a 40-mg generic version of
Copaxone into the market (20mg generic Copaxone is already on the market). The
document is also likely to undermine the confidence of FDA officials, leading
to considerable delay in approval of the Momenta's generic drug for 40 mg
Copaxone.
Teva is currently in a
court case concerning the patents that protect Copaxone against generic
competition (for the 40mg version). However, most analysts believe Teva will
lose the case, and that the generic product will be allowed to enter the market
in 2017.
Former Valeant CEO and CFO being probed for accounting fraud
In the US, an ongoing criminal probe into Valeant Pharmaceuticals is focusing on the extent to which the former chief executive officer – Michael Pearson – and former chief financial officer – Howard Schiller – allegedly hid a relationship with a specialty pharmacy – Philidor Rx Services – from insurers.
Pearson was the key
driver behind Valeant’s growth, which relied
on price-gouging as a growth strategy. Pearson bought older medicines and hiked
their prices manifolds to push up profits.
Federal prosecutors are reportedly exploring potential charges of accounting fraud in connection with Valeant’s ties with Philidor Rx Services, a Bloomberg news report said. Valeant used its ties with Philidor to steer
prescriptions and boost reimbursements for its medicines.
For now, the probe is
examining actions taken by Pearson and Schiller, though sources say others,
such as Philidor executives, may also be charged.
Impressions: 4715
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#PharmaFlow by PHARMACOMPASS
03 Nov 2016
