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Biotechnol Healthc. 2012 Fall; 9(3): 5–6.
PMCID: PMC3474454

Biologics Clinical Trials, Research, and FDA Actions

“Frustrating” pretty much sums up the treatment of Alzheimer’s disease. Available treatments ease symptoms in some patients, but only temporarily — and many physicians think they are given too late. No breakthrough drugs have made it to market in two decades, let alone a disease-changing agent.

Hope for a such a treatment took a hit when Janssen and Pfizer shuttered analysis of four late-stage studies of an IV formulation of bapineuzumab after topline results of the first two trials failed to show improvements in cognitive and functional performance. The first study was limited to patients with the apolipoprotein epsilon 4 (ApoE4) genotype, and many observers did not expect success in this population. Hopes were higher that the antibody, believed to stop disease progression by breaking up amyloid beta, would be more successful in a second study involving non-ApoE4 carriers, but it did not. Phase 2 research into a subcutaneous formulation continues.

The bapineuzumab studies have reduced expectations for solanezumab, a Lilly entry that also strives to break up amyloid proteins. A phase 3 study is due out this fall; a phase 2 trial showed no benefit for patients.

Head-to-head trials

Payers long to see more head-to-head trials of biologics, and lately, results of several such studies have been reported. Shionogi says a regimen of its integrase inhibitor dolutegravir with abacavir/lamivudine suppressed the HIV virus in 88 percent of patients at 48 weeks versus 81 percent among those given Gilead’s Atripla, demonstrating a better safety profile. In another study, Shire’s enzyme replacement velaglucerase alfa (Vpriv) significantly improved lumbar spine bone density in Gaucher’s patients whereas Sanofi’s imiglucerase (Cerezyme) did not. Onyx reported that carfilzomib (Kyprolis), on its way to FDA approval (see table, page 6), bested bortezomib (Velcade) in progression-free survival when patients with relapsed multiple myeloma were given one or the other in combination with dexamethasone.

The head-to-head study sure to get payers’ attention was presented at the European League Against Rheumatism in June — Roche’s tocilizumab (Actemra) against Abbott’s cash cow adalimumab (Humira). In a phase 4 trial, tocilizumab achieved ACR-20 in 65 percent of rheumatoid arthritis (RA) patients after 24 weeks, compared with 49 percent for adalimumab.

Immunomodulatory diseases

Celgene’s oral PDE4 inhibitor apremilast disappointed in a phase 2 study in patients with RA. Combined with methotrexate, apremilast missed statistical significance for ACR-20 improvement versus placebo. But in a phase 3 study in patients with psoriatic arthritis (PsA), apremilast demonstrated significantly better ACR-20, −50, and −70 outcomes than placebo.

Celgene has high hopes for apremilast. Data from four more phase 3 studies — two in PsA, two in psoriasis — are due by the end of the year. Celgene is also conducting a phase 3 study in patients with ankylosing spondylitis and a phase 2 study of apremilast monotherapy in RA patients.

Other trials of note

Merck says topline results of a 16,000-patient study of odanacatib, a cathespin-K inhibitor in development to reduce fracture risk in postmenopausal women with osteoporosis, were favorable. Odanacatib is a potential competitor for Amgen’s denosumab (Prolia). ... Merck’s hopes for expanding use of cetuximab (Erbitux) dimmed after the drug did no better than chemotherapy in preventing the growth of stomach tumors. … In a phase 2b, 24-week trial of 449 patients, Ophthotech’s Fovista in combination with Genentech’s ranibizumab (Lucentis) improved vision better (10.6 letters) in age-related macular degeneration patients than did ranibizumab alone (6.5 letters). Fovista is an antiplatelet-derived growth factor agent. Ranibizumab inhibits vascular endothelial growth factor.

FDA panel watch

Two FDA advisory panels gave votes of confidence to two specialty drugs. The FDA’s Antiviral Drugs Advisory Committee voted 13 to 1 to recommend approval of Gilead’s Quad, the four-in-one HIV pill. Gilead then submitted a new drug application for elvitegravir, an integrase inhibitor for treating HIV-1 and a component of Quad. Meanwhile, Pfizer, seeking approval for its oral JAK inhibitor tofacitinib in RA patients who fail TNF inhibitors, got an 8 to 2 favorable vote from the FDA’s Arthritis Drug Advisory committee despite lingering concerns about cancers and infections.

American Society of Clinical Oncology 2012 Annual Meeting highlights and payer reaction are reported on page 7.

Date (type)ManufacturerDrug (trade name); administrationIndicationNotes
New marketing approvals
May 1 (NDA)Pfizer/Protalixtaliglucerase alfa (Elelyso); IV infusionGaucher diseaseOrphan long-term enzyme replacement therapy
June 8 (BLA)Genentechpertuzumab (Perjeta); IV infusionHER2+ metastatic breast cancer, in combination with trastuzumab (Herceptin) and docetaxelPertuzumab is a component of T-DM1, an antibody-drug conjugate (see ASCO roundup, page 7)
July 20 (NDA)Onyxcarfilzomib (Kyprolis); IV injectionMultiple myeloma, in patients who have failed bortezomib (Velcade) and an immunomodulatory agentApproved on phase 2, single-arm study; needs of patients out of options outweighed concerns about cardiovascular safety
ManufacturerDrug (trade name)Type of drugProposed useNotes
Fast track and priority review designations
Onyx/Bayerregorafeniboral multikinase inhibitorMetastatic colorectal cancerFDA agreed to priority review on June 28; decision by late October
Pfizertafamidis (Vyndaquel)selective stabilizer of the transthyretin proteinTTR-FAPFDA issued a Complete Response Letter June 18 asking for second efficacy study
EdimerEDI200recombinant proteinXLHEDFast track granted June 12; XLHED causes inability to regulate body temperature, potentially resulting in hyperthermia

BLA=biologics license application, NDA=new drug application, TTR-FAP=transthyretin familial amyloid polyneuropathy, XLHED=X-linked hypohidrotic ectodermal dysplasia.

Sources:, FDA, FierceBiotech, manufacturers’ news releases and product labeling, weblogs, and wire reports.

The same arthritis committee decided that trials for Regeneron’s rilonacept (Arcalyst) were too short to prove safety and efficacy in prevention of gout flares, voting 11 to 0 against recommending the new indication. Rilonacept is marketed for cryopyrin-associated periodic syndromes.

Did you hear?

Cancer Research published pre-clinical findings suggesting that some anti-HIV compounds could prevent metastasis in women with aggressive breast cancers. The study focuses on CCR5 antagonists, including maraviroc (Selzentry). … Results of federally funded clinical trials should be publicly reported, but negative results often die in a desk drawer somewhere. Now, a bill moving through Congress would force repayment of federal research grants by investigators who don’t publish results on Clinical, and would make those researchers ineligible for future grants. … The United Kingdom’s National Institute for Health and Clinical Excellence declined coverage of bevacizumab (Avastin) for breast cancer, citing insufficient evidence of better overall survival. Roche blasted back, protesting that NICE has denied 9 of 10 end-of-life oncologic agents.


All clinical trials described in Drug Track are phase 3, randomized, controlled studies unless otherwise specified.

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