This week, Phispers has news from across the world. While China is trying to speed up approval of drugs by accepting data from overseas trials, the US achieved record approval of generic drugs last fiscal. In India, pharma companies may face legal action for releasing effluents into a lake in Hyderabad that killed thousands of fish last week. In France, a reformulated thyroid pill from Merck led to severe side effects in patients. And, there was more bad news for Israel’s Teva as its competitors won approvals from regulators in the US and Europe to market cheaper versions of its blockbuster multiple sclerosis drug — Copaxone.
Data-integrity uncovered in AstraZeneca’s US$ 4 billion Acerta buy
In February 2016, pharma giant AstraZeneca had invested US$ 4 billion in acquiring 55 percent stake in Acerta Pharma — a biopharmaceutical company based in the Netherlands and the US. The acquisition provided AstraZeneca with a cancer drug under clinical trials — acalabrutinib.
An AstraZeneca press release issued at the time of acquisition had said: “Acalabrutinib is a highly selective, irreversible, second generation BTK inhibitor, with approximately 1,000 patients treated to date in clinical studies across the entire development programme.”
“The data, published as an abstract in August 2015 in the journal Cancer Research, reported a therapeutic benefit of acalabrutinib in a mouse model of pancreatic cancer,” the report said. The drug is now in human trials.
Additional trials published in the New England Journal of Medicine and Blood in 2015 showed acalabrutinib had “promising safety and efficacy profiles in patients” with relapsed chronic lymphocytic leukemia.
However, investigation into the data underlying the 2015 abstract revealed some of it was falsified. As a result, the journal retracted on the abstract.
Interestingly a few weeks ago, acalabrutinib had won breakthrough therapy status at the US Food and Drug Administration (US FDA) along with an accelerated review plan for its first approval.
However, all news was not bad news for AstraZeneca. Its innovative treatment for a type of lung cancer won “breakthrough” designation by the US FDA. The endorsement is for therapy Tagrisso for use in the US by patients with previously-untreated non-small cell lung cancer and a genetic mutation known as EFGR. This paves the way for fast-track approval of the drug.
Dead fish in Hyderabad leads to pharma majors being booked
for fouling lake water
Pharmaceutical companies in India — such as Hetero Pharma, Aurobindo Pharm, Mylan, SMS Pharma, Vantec and Sriram — that have their manufacturing facilities in Kazipally industrial area and Industrial Development Area (IDA) have been booked under a case for “fouling water of public spring or reservoir”.
This happened last week after the Gandigudem lake, which is barely a few meters away from Hyderabad's Outer Ring Road (ORR), reported hundreds of bloated, dead fish washed ashore after it rained heavily. The 266-acre lake is situated near the IDA.
The lake has been plagued with pollution for a while now. According to news reports, the Pollution Control Board (PCB) had found traces of chloromethane, a solvent used in the pharma industry, in the samples of the water and dead fish collected from the lake. The diluted traces of the chemical in the lake confirm contamination.
Officials said that 230,000 fish had been washed ashore within a span of two days, causing heavy loss to the fishermen dependent on the lake. According to an official, the fish lost was worth US$ 230,038 (Rs 15 million)
These companies have been booking under Section 277 (fouling water of public spring or reservoir) and Section 278 (making atmosphere noxious to health) of the Indian Penal Code.
A video of a news report on the story can be viewed here.
China to accept data from overseas trials in order to speed up drug
China plans to speed up approval of drugs, and will accept data from overseas clinical trials in order to facilitate that. The move could be a boon for international drugmakers as well as for patients who often face lengthy delays for new medicines to reach the market.
China has approved just over 100 innovative new drugs in the last 15 years — about a third of the drugs approved in the developed markets. This is the key reason behind the country taking this step to speed up drug approvals.
The move also seeks to address high medicine costs, and improve access to healthcare for China’s 1.4 billion population.
The Chinese Cabinet will also look into improving the protection of medical intellectual property and boost the number and quality of clinical trial testing centers in China. However, the proposals contained no timeline for implementation.
In March this year, China had proposed ways to speed up approvals for imported drugs, including reforming clinical trial requirements.
Merck’s French reformulation of most prescribed US drug leads to severe side effects
Popular thyroid drug Levothyroxine reportedly received many complaints of severe side effects from patients in France. The drug works as a stand-in for the hormone thyroxine in patients suffering from hypothyroidism, a condition that affects the body’s metabolism.
According to a Reuters report, French police searched German drugmaker Merck KGaA’s plant in Lyon last week as part of a probe into complaints by patients about changes to its thyroid drug Levothyrox.
In March this year, Merck had removed lactose from Levothyrox to make it easier to tolerate and replaced it with citric acid and mannitol, a type of sugar alcohol. The new formulation had been requested by the French medicines regulator ANSM in 2012. According to patients, this resulted in severe side effects such as memory loss, hair loss, weight gain and palpitations.
Around 3 million people in France, 80 percent of them women, use Levothyrox. According to a Medscape article, levothyroxin is also the most prescribed drug in the US. The prescriptions for Levothyroxine (in the US) stood at 112 million in 2012 and 123 million in 2016. The drug was far ahead of the number two drug on the list (Lisinopril — with 99 million prescriptions in 2012 and 110 million in 2016).
Last month, a prosecutor in Marseille had launched a probe into whether Merck had deceived patients with the change in the drug’s formula. Since then, Merck has restored the original drug to the market.
Teva fights to hold market share as competitors receive nod for
its blockbuster drug
Bad news from Israeli generic drug giant Teva Pharmaceutical Industries doesn’t seem to relent. Last week, Teva was taken unawares when its competitors won approvals from regulators in the US and Europe to market cheaper versions of its flagship Copaxone drug for multiple sclerosis.
The launch of the competing products will result in “significant declines” in Teva’s largest product effective this year, Moody’s Investors service said in a note.
On October 3, Mylan said it received approval from the US FDA for the marketing of generic versions of Teva’s Copaxone (glatiramer acetate) in 40 mg and 20 mg dosages. Mylan said it would start shipping the generic version immediately.
According to Bernstein analyst Ronny Gal, Mylan is serving up 25 to 30 percent discounts versus the “prevailing price” on Teva’s Copaxone and Teva is countering it, he added.
Analysts had written off Mylan’s long-delayed generic Copaxone until next year. The approval last week surprised analysts and investors.
Two days later, Alvogen said it had received an approval from European regulators to market the 40 mg dose of generic Copaxone in Europe. Alvogen has been selling the 20 mg dose of the drug in Europe.
These approvals could mean a “downside” to both revenue and profit estimates for 2018, Citi’s Liav Abraham said.
Generic drug approvals in US hit all time high; Indian firms
corner large chunk
The US FDA approved a record 763 generic drugs in the US fiscal year that ended on September 30, 2017. Amongst these, Indian companies accounted for nearly 40 percent of the approvals, a news report published in the Mint said. The regulator also gave 174 tentative approvals during 2016-17.
In comparison, the US FDA had approved 651 generic drugs last year, the latest Activities Report of the Generic Drug Program of the FDA said.
As per the FDA report, total filings of abbreviated new drug applications (ANDAs) for generic drugs with the US FDA rose to 1,292 in 2016-17 from 852 a year ago.
According to analysts, the increasing number of product approvals and filings indicate an increase in competitive intensity in the US, which is a major market for many Indian drug companies. This would also result in more pressure on drug pricing.