Replies to post #61786 on Biotech Values

[DewDiligence]

Will MNTA be required to add over-sulphated
chondroitin sulphate to its generic Lovenox?
(I’m joking, of course).

http://www.reuters.com/article/marketsNews/idINWLB044120080424

>>
UK Warns on Impurity in Sanofi’s Clexane

Thu Apr 24, 2008 8:33am EDT

LONDON, April 24 (Reuters) - Some batches of Sanofi-Aventis's blood thinning heparin injection Clexane [a.k.a. Lovenox] on the UK market contain low levels of the impurity over-sulphated chondroitin sulphate, the country's drug watchdog said on Thursday.

The Medicines and Healthcare products Regulatory Agency said there was currently no evidence this was associated with any risk to patients. Doctors could continue to use the product but should remain vigilant to any adverse reactions.
<<

[DewDiligence]

Post-mortem on the contaminated-heparin story:
the culprit was indeed OCOS, the contamination
was deliberate, and it was probably motivated
by a shortage of available pigs in China. (Ram
Sasisekharan is a founder and director of MNTA.)

http://news.yahoo.com/s/nm/20081203/hl_nm/us_heparin_contamination_1

›Contaminant Confirmed in Tainted Heparin

By Gene Emery
Dec 3, 2008

BOSTON (Reuters) – The contaminant linked to dozens of deaths and hundreds of illnesses from tainted batches of the blood thinner heparin manufactured in China was chemically related to a dietary supplement used to treat joint pain, researchers confirmed on Wednesday.

The U.S. Food and Drug Administration announced in March that it believed the contaminant to be over-sulfated chondroitin sulfate or OSCS, a modified version of the joint supplement chondroitin sulfate.

Wednesday's announcement was confirmation of that finding and means that new tests put in place to scan for OSCS contamination should be effective.

Maker Baxter International Inc. launched two recalls of its heparin products -- used in heart surgery and kidney dialysis -- on January 17 and February 28 after 113 patients in 13 states suffered adverse reactions such as low blood pressure, nausea and shortness of breath.

Ram Sasisekharan of the Massachusetts Institute of technology and colleagues at the Centers for Disease Control and Prevention found that more than 98 percent of the 152 reactions they studied were at health centers where the heparin was contaminated by OSCS.

"Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3 percent) occurred after the administration of OSCS-contaminated heparin," they wrote in the New England Journal of Medicine.

OSCS can thin blood, passes the quality control screening test used at the time and is far cheaper to acquire than getting real heparin from pig intestines.

Sasisekharan said in a telephone interview that the study made no attempt to determine how the heparin became contaminated, but the chondroitin was purified. "It is hard to explain a natural biological source for this," he said.

In the samples his group examined, up to 35 percent of the heparin, by dry weight, was actually OSCS.

Sasisekharan said the contamination coincided with the spread of a virus that had created a shortage of pigs in China. "There weren't enough pigs around, you're not able to get enough heparin, and the over-sulfated chondroitin passes the test that is in place to screen heparin," he said.

A key unanswered question is whether patients who survived exposure to the tainted heparin still may have health problems.

"There were countries that were still using the contaminated heparin because of an acute shortage, so they took the risk," said Sasisekharan. "We have no idea what the long-term exposure implications are."‹

[DewDiligence]

Obama FoB Plan May Get Early Push by Momenta

[No new info in this Bloomberg write-up, which sloppily refers to Lovenox as a biologic. The best part is the quote from CEO Craig Wheeler about ¾ of the way down.]

http://www.bloomberg.com/apps/news?pid=20601103&sid=a4qYpDq065g0

›By Catherine Larkin
March 10, 2009 00:01 EDT

March 10 (Bloomberg) -- Momenta Pharmaceuticals Inc. may become the first drugmaker to win U.S. clearance to sell generic versions of a biotechnology medicine, getting a head start on President Barack Obama’s plan to trim health-care costs by making such copycats commonplace.

Brand-name biotech treatments, which can cost individual consumers or their health plans as much as $200,000 a year, are made from living cells, unlike pharmaceutical medicines that are chemical-based. Generic-drug companies can’t sell copies of brand-name biotechnology drugs because the 1984 U.S. law allowing versions of conventional pills doesn’t provide a system to measure safety and approve so-called biogenerics.

Momenta, an unprofitable, 8-year-old company in Cambridge, Massachusetts, may be cleared this year to copy the blood- thinner Lovenox, made by Paris-based Sanofi-Aventis SA, said Momenta Chief Executive Officer Craig Wheeler. The approval, allowed under a regulatory quirk, may come before Obama’s plan is enacted, leapfrogging a similar effort Teva Pharmaceutical Industries Ltd., of Petah Tikva, Israel, the world’s biggest maker of generic drugs.

“We have a chance to make an impact that’s potentially greater and faster than most drug companies out there,” Wheeler said in an interview.

Momenta sank 4.3 percent, or 32 cents, to $7.12 yesterday in Nasdaq Stock Market composite trading. The drugmaker fell 20 percent in the 12 months before today as investors await Food and Drug Administration action on the Lovenox copy.

Not all drugs made from living cells are considered by the FDA through the agency’s biologics license application process. For a variety of reasons, some categories of treatments made using living cells, including insulin, human growth hormone and heparins, were approved under the process for conventional medications.

$4.03 Billion in Sales

Lovenox, which generated 2.74 billion euros ($4.03 billion) in sales last year, is in the heparin family.

Heparins are composed of chains of sugars, rather than sugars and proteins. That makes them simpler to copy than some other biotechnology drugs, and opens the way to approval. While simple heparins made from pig intestines are already available generically, Lovenox, which added patented processes that allowed the drug to be given at home rather than in a hospital, would be the first biotechnology brand-name medicine with interchangeable copies.

Teva and closely held Amphastar Pharmaceuticals Inc., of Rancho Cucamonga, California, applied in 2003, two years before Momenta, to sell copies of Lovenox. Momenta’s technology, developed at Massachusetts Institute of Technology in Cambridge, has proven superior, and the company has a better relationship with the FDA, said Joseph Schwartz, a Leerink Swann & Co. analyst in Boston, in a Jan. 5 note to investors.

‘Corner This Market’

“Momenta stands out among the crowd with its follow-on biologics strategy,” Schwartz wrote. “It is in a unique position to corner this market.”

Ronny Gal, an analyst at Sanford C. Bernstein & Co. in New York, said that market may top $12 billion annually in U.S. sales by 2015.

Americans spend $60 billion a year on biotechnology drugs for cancer, diabetes, rheumatoid arthritis and other illnesses.

European regulators already allow copies of some biologic drugs. Obama’s budget proposal last week backed biogenerics to slash health-care spending, which is projected to grow faster than the economy in the next decade. Drugmakers, insurers and patient groups support creating a path for FDA approval.

Opponents to approving biogenerics say differences in how biotechnology medicine is made can change how the body reacts to it, cutting effectiveness or even causing life-threatening allergic reactions.

Size Matters

“Because of the differences in size and complexity, the large molecules are much more sensitive to things like temperature and it is much more difficult to replicate them,” said Sara Radcliffe, vice president of science and regulatory affairs at the Biotechnology Industry Organization trade group in Washington, in a March 6 interview.

Teva; Sandoz, the generics arm of Swiss drugmaker Novartis AG; and Hospira Inc., of Lake Forest, Illinois, have won European approval to sell copies of three drugs as “biosimilars.” The European Medicines Agency has said they shouldn’t be considered automatically interchangeable with brand-name products by pharmacies or insurers.

The U.S. FDA took three years studying Momenta’s unusual drug-making method before a breakthrough last year.

That was when government scientists sought the company’s help in identifying the contaminant in Chinese-made heparin, tied to at least 149 American deaths. The FDA and Momenta published their findings last year in the New England Journal of Medicine and in the journal Nature Biotechnology.

‘Broader Awareness’

“We couldn’t have asked for a better way to introduce the technology to the agency on a large basis,” Wheeler said. “I can guarantee that there’s a much broader awareness of the power of the analytical tools that we have.”

While Teva and Merck & Co., of Whitehouse Station, New Jersey, anticipate human tests of biogeneric products now in development, Momenta’s copies won’t need as much research to prove they’re as safe as brand-name versions, Wheeler said. That will allow faster and cheaper FDA approval than Momenta’s competitors are likely to receive, he said.

Proving their product is the same structurally may eliminate the need for extensive clinical tests because you wouldn’t be able to tell the brand name and the copy apart, Momenta has said.

Sandoz bought a 12 percent stake in Momenta in 2006 and agreed to pay as much as $263 million to help it copy Lovenox and three other biologic drugs. Momenta junked one of those projects because of competition. Another aims to duplicate the multiple sclerosis drug Copaxone, made by Teva. The FDA accepted Sandoz and Momenta’s application to copy Copaxone in July.

Lovenox is Sanofi’s biggest product. The Paris-based drugmaker has urged the FDA to reject generics of that medicine, because the Lovenox molecule isn’t “fully characterized” and can’t be duplicated. Teva says the same thing about Copaxone, which generated $2.26 billion in 2008.‹