Is Aventis following in the footsteps of Bristol-Myers Squibb?
All will remember that Bristol-Myers Squibb paid a sizeable sum (US$2 billion) for ImClone shares, shortly before the FDA rejected the first submission of the file of IMC-225. Aventis, another pharma giant, has agreed to pay up to US$480 million to Genta, a small biotechnology company in New Jersey. Financial reporters say that the Aventis deal shows that pharmaceutical companies, many of which are not producing enough new drugs on their own to sustain growth, are still willing to pay heavily for drugs that are close to reaching the market. But Aventis is cautious and more than half of the US$480 million will not be paid until Genasense (an antisense cancer drug) wins various approvals. Genasense blocks Bcl-2 and allows cells to undergo apoptosis. Studies are near completion in melanoma, multiple myeloma and chronic lymphocytic leukemia.
Another cytotoxic wins orphan drug status
Bryostatin-1, now of the German company GPC Biotech, was awarded orphan drug status in esopheageal cancer therapy by the EU, as reported by the Wall Street Journal Europe on 14 May 2002. This means 10 years of protection for commercialization of the drug, which is in phase II trials for this indication. In the USA, bryostatin-1, associated with paclitaxel, has had a similar status since December 2001.
Is Serono using illegal commercial tactics or are others trying to hurt Serono?
The attorney general of Boston is investigating the promotion of Serostim by Serono, an anti-cachexia drug approved in 1996 by the FDA for AIDS patients. Serono, it is alleged, might have given some kick backs to stimulate prescription and dispensing of the drug. Some pharmacists are stated to have illegally sold this drug to body-builders at a cost of US$21 000 for a 12-week course. The Boston Globe 9 May 2002 reports that there may also be some Medicaid fraud involved. But, it also reminds the reader that such investigations have often led to a filing of the case. One should remember that Serono recently won against Biogen, a Massachusetts firm, in a fight about the commercialization of interferon-ß for the treatment of multiple sclerosis.
Cancer Research UK: a new mutual fund for the pharma industry?
A British biotechnology company, Antisoma, seems to have been saved from financial ruin when the UKs largest cancer research charity, Cancer Research UK, formed in February when the Imperial Cancer Research Fund (ICRF) merged with the Cancer Research Campaign, stepped in. Sir Paul Nurse and Gordon McVie, are joint Director Generals of Cancer Re-search UK. The ICRF had originally developed pemtumomab, and licensed it to Antisoma. The product is in phase III trials for ovarian cancer and in phase II for gastric cancer, but Antisoma only had £5.2 million in cash at the end of 2001not enough to continue ongoing phase III ovarian cancer trials. Antisoma has asked its shareholders to provide £22 million, of which Cancer Research UK is taking up to £1 million. According to Nature Medicine 1 April 2002, Cancer Research UK has interests in several other drug development companies and owns just over 5% of Cyclacel of Dundee, UK, and KuDOS of Cambridge, UK, worth about £4.5 million in total. Pemtumomab, formerly called Theragyn, is a murine monoclonal antibody (HMFG1) directed against the PEM marker, which is known to be overexpressed in epithelial tumor cells such as ovarian and gastric cancers. In its therapeutic form, the antibody is conjugated to the ß-emitting radioisotope, yttrium-90. It has orphan drug status in both the USA and the EU. However, Antisoma ran into problems last June, when the USA FDA began taking a more cautious approach to biologicals, especially radioimmunotherapeutics. The FDA said it needed proof of pemtumomabs efficacy against ovarian cancer to the P = 0.01 statistical level, instead of the usual P = 0.05. This requires a trial expansion from 300 to 420 subjects, costing Antisoma an extra £10 million.
The swing of the pendulum? Endostatin criticized in the lab, but of interest clinically?
Two papers appeared in Molecular Therapy, 1 April 2002, that, once again, fail to replicate the glowing results from the Harvard University lab of Judah Folkman, which won endostatin worldwide attention in 1998. Philippe Leboulch of Harvard University and the Massachusetts Institute of Technology, Connie Eaves of the Terry Fox Laboratory in Vancouver, and colleagues, transferred DNA encoding a secretable form of endostatin into mice. They saw endostatin surge to continuous levels of 750% normal in serum, but there was no change in either the growth of new blood vessels or in tumor size. Even when the researchers directly injected the protein, as described by Folkman in his original paper, they could not detect it in the serum. According to BioMedNet News, Steven Libutti, a senior investigator at the US National Cancer Institute who specializes in the study of cytokines and angiogenesis, says the only reason the papers will get attention is because they have endostatin in them. "Its a shame there is so much interest in a negative study when a pile of papers indicates there is an effect", Libutti told BioMedNet News. But George Yancopolous, chief scientific officer of New York-based Regeneron Pharmaceuticals, predicted that the "historic skepticism" regarding endostatin will continue for a long time. Folkman is reported to have told BioMedNet News that 180 patients have enrolled in trials and 1800 are waiting to enroll. After 8 months of wearing a portable pump, some patients began to have regression, and 10 have switched to subcutaneous delivery, as with insulin, Folkman says.
Chernobyl 16 years later
French authorities face a class action legal suit by another 200 patients with thyroid disease. They claim, following the claim of an initial group of 200 in March 2001, that France did not fully disclose the extent of radioactive contamination and allowed its population to take risks which have now, 16 years later, lead to dire consequences. The head of the Ukraine Radioactive Safety Commission, Mr Dmitri Grodzinski, has also recently stated that radioactivity continues to leak from the Chernobyl site, which 6 million people live near. In Germany some Bavarian game and mushrooms seem to still have abnormally high levels of radioactivity. This reminds us of the fact that radioactive waste is not biodegradable with the same ease as toilet paper; a terrible reminder in moments where India and Pakistan seem to be close to using their nuclear weapons.
Is the human genome of Celera the genome of its past President?
Craig Venter, the American geneticist who was the boss of Celera Genomics claims, according to Le Temps, 2 May 2002, that the DNA on which the scientists worked was his own, not the result of a pool of 20 anonymous donors. He was found to have inherited ApoE4, which can lead to abnormal lipid metabolism and a risk of Alzheimers. Venter had to resign from Celera recently because of insufficient financial results under his leadership.
Roche and Novartis? Or will it be GlaxoSmithKline and Bristol-Myers Squibb? And what about Pfizer?
Andrew Fellows, analyst at Banque Pictet & Cie, is convinced that Novartis has increased its participation in Roche. The need to find new ways to achieve a return on investment (ROI) polarizes some management teams in drug companies as many patents are running out, to the order of approximately US$60 billion in sales in the US market alone in 2005. As an example, Prozac, from Eli Lilly, is now worth a fraction of the US$2.5 billion it represented before generics were introduced. Research and development is expensive, representing for Pfizer, the largest pharma company today, US$5 billion, roughly equal to the sum of the amounts Novartis and Roche spend. They would spend less together and also save on the costs of the huge sales forces each company maintains, a total of >80 000 collaborators for the pharma industry in the USA alone. Pfizer and GlaxoSmithKline each have 8000 reps and Novartis 5500 reps. Thus, mergers are a way to boost the ROI.