Replies to post #68657 on Biotech Values

[Preciouslife1]

Heparin's Deadly Side Effects

http://www.time.com/time/magazine/article/0,9171,1858870,00.html
By Bill Powell/Shanghai
Thursday, Nov. 13, 2008

Leroy Hubley, 72, lost his wife and son to heparin-related complications
ROBERT ADAMO FOR TIME
Leroy Hubley, 72, married for 48 years and a father of three, has lived through tragedy no one should endure once, and he did so twice in the span of a month. Bonnie Hubley, his wife, had polycystic kidney disease, in which cysts grow in the kidneys, often becoming so large that the kidneys fail and have to be replaced. All of the Hubley children inherited the genetic disease. In 1995, Bonnie had a kidney transplant, and in October of last year, her body began to reject the replacement kidney, requiring her to start dialysis.

A month earlier and half a world away, a team of quality-control specialists from Baxter International, the big multinational health-care company (2007 sales: $11.26 billion) based in Deerfield, Ill., arrived in Zhejiang province, China, about two hours by car from Shanghai, to inspect a facility owned by one of its key suppliers. CZ-SPL is a joint venture controlled by Scientific Protein Laboratories LLC (SPL), a Waunakee, Wis., company started in 1976 by Oscar Meyer, of hot-dog fame. (The connection: pigs naturally produce proteins used in pharmaceuticals.) CZ-SPL makes a key ingredient, what in the pharmaceutical business is called an active pharmaceutical ingredient, or API, for a drug called heparin, a blood thinner that is widely used by kidney-dialysis and postsurgical patients to prevent blood clots. The team found little unusual and gave the facility a clean bill of health.

On Dec. 17, after two months of dialysis using heparin produced by Baxter, Bonnie Hubley was rushed into intensive care. She had developed diarrhea, vomiting and eventually severe pain in her chest and abdomen. She deteriorated rapidly and by Dec. 19 was unconscious and on a breathing tube. Stunned doctors at the Toledo, Ohio, hospital told Leroy there was no hope. "She was gone," he says. So with "Christmas carols playing in the background," he says, "we said our goodbyes, and my wife of 48 years drifted away."

Three weeks later, his 47-year-old son Randy, also a dialysis patient and a heparin user, suddenly had symptoms similar to those that had killed his mother. Shockingly, he died on Jan. 15, as his wife Colleen, a dialysis nurse (they had met at the clinic years earlier), frantically and futilely tried to revive him. An uncomprehending family buried Randy Hubley next to his mother in Toledo.

Now add tainted baby milk to a seemingly unending stream of foods, drugs, pet foods and toys that over the past two years have killed or injured thousands worldwide. These products all have three words in common: MADE IN CHINA. A large state-owned Chinese company, Sanlu Group, based in Hebei province in central China, as well as several smaller companies, apparently diluted milk products with an additive called melamine. Industrial-grade melamine is a masking agent used to hide the dilution of protein, in this case in milk products, including an infant formula widely popular in China. Nearly 53,000 small children in China have developed kidney stones, four have died, and product recalls have spread to 11 countries, including the U.S. The recall list includes seven instant-coffee and milk-tea products made in Taiwan using Chinese milk. (Melamine also tainted the pet food that harmed so many animals in the U.S. last year.)

The rest of the article is in the link above. Thanx.


PL1

[Preciouslife1]

Deal watch: Ablynx and Merck Serono collaborate on next-generation antibody products

http://www.nature.com/nrd/journal/v7/n11/full/nrd2754.html
Nature Reviews Drug Discovery 7, 881 (November 2008) | doi:10.1038/nrd2754

Ablynx and Merck Serono have entered into an agreement to co-discover and co-develop nanobodies — a class of antibody-derived therapeutic proteins — against two unspecified targets in oncology and immunology. Under the agreement, Ablynx receives an upfront cash payment of 10 million euros, and the companies will equally share all R&D costs.
Total development and commercial milestones, depending on if and when Ablynx exercises options for partly or fully opting out of the partnership, could reach up to 325 million euros.

This agreement follows several similar collaborative deals/acquisitions involving large pharma companies and companies developing next-generation antibody derivatives (Table 1), reflecting the growing interest in alternatives to monoclonal antibodies over the past decade (Nature Biotech. 23, 1126–1136; 2005). Several types of antibody fragments, as well as alternative scaffolds (Nature Biotech. 23, 1257–1268; 2005), are now in clinical trials and Genentech's ranibizumab (Lucentis) (Nature Rev. Drug Discov. 5, 815–816; 2006) provides a successful example of an antibody fragment that has already received FDA approval.

Nanobodies harness the structural and functional properties of antibodies from camelids, which contain a single variable domain, and are small enough to penetrate cavities in target proteins, such as enzyme active sites. Several other analogous technologies being pursued are highlighted in Table 1.

The growing popularity of these technologies stems from the advantages compared with full-size antibodies.
"They can easily be selected or engineered for highly specific binding to a target antigen, while retaining the inherent stability and solubility associated with immunoglobulin domains," says Mike Clark, University of Cambridge, UK, who has been working on therapeutic antibody technologies for more than two decades.

"Owing to their small size, they are also more easily produced than traditional antibodies, in a range of different expression systems, including bacteria and yeast," he adds. This could reduce manufacturing costs compared with traditional antibodies, which are often produced in mammalian expression systems. The fragments can also be engineered into more complicated products, such as bi- or tri-specific complexes, or modified to increase their half-life, which is typically much shorter than traditional antibodies.

Immunogenicity issues with next-generation antibody-like products represent a potential major challenge, although Clark thinks that the wealth of experience with antibody-based therapies in general will help address this.
These products also lack an inherent effector function, which might be important in some diseases. Nevertheless, "since the desirable properties of antibodies vary according to disease, having multiple tools in your toolbox is what it is all about," concludes Clark.

[DewDiligence]

ANTICOAGULANT INDEX

[Updates:
new section for Daiichi Sankyo’s DU-176b;
ASH update for Rivaroxaban;
Ablynx ALX-0681 starts phase-1;
Portola Pharmaceuticals’ phase-2 data.
Please see MNTA ‘ReadMeFirst’ for info on M118.]


General
#msg-25160571 Anticoagulant market has large potential (WSJ)
#msg-26899903 Anticoagulant market has large potential (graphic)
#msg-26451612 Venous thromboembolism is a big, big problem
#msg-18759853 Overview of the new oral anticoagulants
#msg-26701803 Technical overview of traditional anticoagulants


Xarelto (rivaroxaban)
#msg-30972846 EMEA approves Xarelto for VTE prevention
#msg-31073048 JNJ submits NDA for VTE prevention
#msg-34103973 Phase-3 data in VTE prevention (JNJ PR)
#msg-29661234 Phase-3 data in VTE prevention (Reuters)
#msg-31857009 Bayer accelerates Xarelto development
#msg-33517140 Phase-2 data in ACS
#msg-29662519 Rivaroxaban rationale
#msg-24337258 Bayer plans 50,000(!)-patient study


Apixaban
#msg-31742223 Apixaban fails vs Lovenox in phase-3
#msg-32024540 Tepid phase-2 results in ACS
#msg-19134406 PFE, BMY ink $1B collaboration
#msg-29928836 Seventh and eighth phase-3 trials begin
#msg-21044973 Apixaban non-inferior to Warfarin in phase-2


Pradaxa (dabigatran)
#msg-32382343 NICE approves Pradaxa in only six months
#msg-27956748 EU approves Pradaxa for VTE prevention
#msg-26086079 BI completes enrollment of huge AF trial
#msg-25152872 BI starts phase-2 in ACS
#msg-21155926 Dabigatran non-inferior to Lovenox in VTE prevention


DU-176b
#msg-34100821 Phase-3 begins in AF
#msg-34100787 Comparable Safety to Warfarin in AF (phase-2)
#msg-31950663 Phase-2 data in hip surgery


Lovenox
#msg-26739674 US market share
#msg-28936334 Where Lovenox sales come from
#msg-33630772 Lovenox not more costly than Arixtra (CHEST 2008)
#msg-11669012 Lovenox more economical than unfractionated heparin


Miscellaneous (in alphabetical order)
#msg-34108151 Ablynx ALX-0681/ALX-0081
#msg-10569101 Arixtra bests Lovenox in ACS
#msg-27043616 ART-123 from Artisan Pharma
#msg-33309473 ARYX ATI-5923: A safer warfarin?
#msg-22938795 AVE5026 and otamixaban (SR123781 dropped Feb08)
#msg-31161411 AZD0837 comes out of the closet
#msg-26298260 Biotinylated idraparinux causes excess bleeding
#msg-30965016 LLY terminates FXa program
#msg-30353872 MYGN MPC-0920 begins phase-1
#msg-31461171 NUVO reports phase-1b data for NU172
#msg-27187973 Paion’s Solulin completes phase-1
#msg-28742653 Paion acquires flovagatran rights
#msg-21106352 Portola’s phase-2 data not impressive (IMO)
#msg-32171800 Regado reports phase-1 data for aptamer