Research, Conferences, and FDA Actions

Biotechnol Healthc. 2008 Sep-Oct; 5(3): 8–10.

PMCID: PMC2706175

Research, Conferences, and FDA Actions

Michael D. Dalzell, Editor

Rheumatology agents

The long-awaited results of the pivotal phase 3 trial of denosumab proved to be good news for Amgen: The bone drug produced statistically significant reductions in the incidence of vertebral, nonvertebral, and hip fractures compared with placebo. Moreover, Amgen reported no major side-effect concerns in the treatment cohort — a departure from smaller studies that suggested an elevated risk of serious infections, such as tuberculosis, or cancer. More than 7,800 women with osteoporosis took part in the 3-year international study.

The positive news for Amgen came on the heels of a British study of its best-selling TNF-α inhibitor, etanercept (Enbrel), that documented prompt remission of rheumatoid arthritis when it is given early in the course of the disease. A regimen of etanercept and methotrexate in patients whose RA had been classified as moderate to severe for less than 2 years led to remission in about half of the 542 people studied. After 1 year, disease progression stopped in 8 of 10 people who received the combination therapy, compared with about 6 of 10 patients who were treated with methotrexate alone.

Hoping to make its own inroads in the RA market, Roche released more positive data from two phase 3 trials of its interleukin 6 receptor blocker, tocilizumab (Actemra). One of the studies, published in Annals of Rheumatic Diseases, evaluated difficult-to-treat patients with moderate to severe RA who had failed previous anti-TNF-α therapies. Half of those receiving tocilizumab achieved ACR20.

Oncology trials

Median survival and time to radiologic progression were 3 months longer for advanced liver cancer patients treated with Bayer’s sorafenib (Nexavar) than those who were given placebo. The multicenter, double-blind, placebo-controlled trial of 602 patients was published in the New England Journal of Medicine. ... Acknowledging that it had lost the race with Bayer to bring a liver cancer treatment to market, Progen Pharmaceuticals abandoned development of its main product, PI-88. The novel antithrombotic had been studied not only for liver cancer but also for skin and lung malignancies, with mixed success.

Ofatumumab (formerly HuMax CD20) hit primary and secondary endpoints in a phase 3 trial in patients with chronic lymphotic leukemia (CLL) who did not respond to methotrexate or TNF-α inhibitors. GlaxoSmithKline, which spent $2 billion to license ofatumumab from Genmab, plans to seek U.S. Food and Drug Administration approval before the end of the year. Ofatumumab also is being investigated for RA, multiple sclerosis, and non-Hodgkin’s lymphoma (NHL). ... In a mid-stage study, bendamustine (Treanda), Cephalon’s infusion therapy for CLL, induced a clinical response in patients with NHL when used in combination with rituximab (Rituxan).

Ark Therapeutics reported positive results from a late-stage trial of sitamagene (Cerepro), its gene therapy for malignant brain tumors. ... Motesanib, one of five Amgen oncology drugs in phase 3 testing, delayed or reversed the growth of thyroid tumors, found a study published in NEJM. ... In high-risk melanoma patients, sargramostim (Leukine) increased mature dendritic cells, which help the immune system recognize cancer cells. Bayer reported results of the prospective phase 2 study. ... A late-stage trial of TroVax, Oxford BioMedica’s therapeutic vaccine for renal cancer, will not hit its endpoint because of too many patient deaths in the trial. A data safety monitoring board said the trial could continue, but wanted further vaccinations discontinued.

Other research of note

Elan and Wyeth will proceed to a phase 3 study to determine the usefulness of bapineuzumab in patients with Alzheimer’s disease. Mid-stage results, presented at the International Conference on Alzheimer’s Disease, showed that bapineuzumab improved 3 of 4 measures of cognitive tasks in Alzheimer’s patients without ApoE4, a genetic variation found in about half of those people with Alzheimer’s and that predisposes them to the condition. But the drug failed to improve dementia symptoms. ... If bapineuzumab makes it to market, it could be the first disease-modifying Alzheimer’s drug available, now that Myriad Genetics and Lundbeck have discontinued development of tarenflurbil (Flurizan). So concluded Decision Resources in an analysis issued after tarenflurbil’s late-stage failure to stop the buildup of toxic plaques.

AtheroGenics’ antioxidant, succinobucol, appears to slow or prevent progression to diabetes in cardiovascular patients with a prediabetic condition, according to data extracted from a 6,000-patient, phase 3 study. ... Topline results from a phase 3 trial of tasimelteon, a novel melatonin agonist, show significant improvements in sleep among adults with chronic primary insomnia. Vanda Pharmaceuticals also is evaluating tasimelteon as a potential treatment of circadian rhythm sleep disorders. ... Novo Nordisk ended its phase 3 trial evaluating coagulation factor VIIa (NovoSeven) as a therapy for bleeding in the brain after a “futility analysis” predicted a low likelihood of positive outcomes. ... While Insmed waits for development of a regulatory pathway for follow-on biologics, it forges ahead with development of INS-19, a version of Amgen’s filgrastim (Neupogen). Insmed reported that in a small trial, INS-19 showed bioequivalence to filgrastim.

SELECTED FDA BIOLOGIC DRUG AND TEST APPROVALS, JUNE–JULY 2008

Action date	Drug or test name (Trade name)	Sponsor	Indication	Dosage form
*New indication*
June 20, 2008	bortezomib (Velcade)	Millenium/Takeda	First-line treatment of multiple myeloma	IV injection
*Molecular test marketing clearance*
July 31, 2008	Pathwork Tissue of Origin	Pathwork Diagnostics	Used for hard-to-identify tumors; determines type of cancer cells present in malignant tumors	Microarray technology

SELECTED FDA ACTIONS, JUNE–JULY 2008

Manufacturer	Drug name (Trade name)	Type of drug	Indication	Notes
*New drug application*
Hemispherx Biopharma	poly I:poly C12U (Ampligen)	Toll-like receptor therapy	Chronic fatigue syndrome	Accepted July 8, 2008
*Biologics license application*
Introgen	Ad5CMV-p53 (Advexin)	Gene therapy	Recurrent, refractory head and neck cancer	Filed June 30, 2008; FDA did not accept
*Orphan drug designation*
Clinuvel	afamelanotide	Melanotan peptide	Erythropoietic porphyrias (severe skin sensitivity to sunlight)	Granted July 28, 2008
*Denials or delays*
Eurand	EUR-1008 (Zentase)	Enzyme replacement therapy	Exocrine pancreatic insufficiency	Received approvable letter June 18, 2008

Sources: FDA, manufacturers’ package inserts and news releases, U.S. Securities and Exchange Commission filings

Did you hear?

An FDA advisory panel expressed concerns about the risk of malignancy and serious infections, but nonetheless voted 7–5 to recommend that etanercept be approved for use in children with moderate to severe psoriasis. The panel expressed the same concerns about ustekinumab but voted unanimously to recommend approval. ... Another FDA advisory panel gave a 10–1 endorsement to tocilizumab for treatment of RA. The FDA is not bound by its panels’ advice, but usually follows it. ... Amgen’s anemia drugs should not be used until a patient’s hemoglobin drops to 10 g/dL, according to new, stricter safety labeling ordered by the FDA. ... Biogen Idec says two more patients taking its powerful MS therapy natalizumab (Tysabri) have contracted progressive multifocal leukoencephalopathy. ... Genentech has advised physicians not to use bevacizumab (Avastin) in combination with sunitinib (Sutent), citing a higher risk of anemia.

After publication of a study that reported hypersensitivity reactions in patients with HIV, the FDA has urged physicians to test for a certain genetic variation before administering abacavir (Ziagen). ... Monogram Biosciences and Invitrogen have introduced two new tests to diagnose HER2-positive breast cancer.

Big pharma is scaling back clinical research in the United Kingdom, pointing to what it sees as the National Institute for Health and Clinical Excellence’s hostility toward high-tech, high-priced therapies. Recent NICE decisions mean the National Health Service won’t pay for bevacizumab and erbitux (Cetuximab) to treat certain cancers. NICE did approve adalimumab (Humira) for treatment of plaque psoriasis.

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