Biologics In Development

Early Results out From NIH-Sponsored CER Study


Katherine T. Adams

Regeneron’s aflibercept (Eylea) injection in patients with diabetic macular edema demonstrated greater improvement in visual acuity than either of two Genentech biologics, bevacizumab (Avastin) and ranibizumab (Lucentis). In the National Institutes of Health-sponsored Diabetic Retinopathy Clinical Research Network comparative effectiveness study, the median number of aflibercept injections was one fewer than either of the comparative products.

Genentech counters that findings of a single trial at one year must be viewed in context of the totality of the evidence establishing the efficacy and safety of ranibizumab. NIH sponsored a comparative study of bevacizumab and ranibizumab several years ago, finding both equally effective in treating age-related macular degeneration.

Immune disorder studies

Amifampridine phosphate (Firdapse) tablets for the treatment of Lambert-Eaton myasthenic syndrome were superior to placebo in a double-blind, randomized withdrawal study. Both primary endpoints — changes in quantitative myasthenia gravis score and subject global impression — were met.

Adalimumab (Humira) reduces abscesses and inflammatory nodules in moderate-to-severe hidradenitis suppurativa (HS), also called acne inversa, according to PIONEER II study data. At 12 weeks, patients with moderate-to-severe HS treated with adalimumab achieved a statistically significant greater response than those given placebo. No approved treatment for HS exists.

Novartis’s secukinumab improved signs and symptoms of adult psoriatic arthritis, compared with placebo, in the FUTURE 1 and FUTURE 2 studies. Secukinumab also improved physical function and quality of life vs. placebo in patients with ankylosing spondylitis, according to the MEASURE 1 and MEASURE 2 studies. The drug stops the action of interleukin-17A, a protein central to inflammation. Regulatory filings are intended for 2015.

Eli Lilly plans to scrap development of tabalumab after the anti–B-cell activating factor monoclonal antibody failed to achieve significant improvement on SRI-5, a measurement of lupus disease activity and response, compared with standard-of-care therapy in the ILLUMINATE-1 trial.

On the cancer front

Patients with Hodgkin’s lymphoma (HL) lived significantly longer without disease progression when given brentuximab vedotin (Adcetris) immediately after an autologous stem cell transplant versus those given placebo, according to results of the randomized AETHERA trial. Adcetris is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of HL. An overall survival analysis will not be available until 2016, though Takeda plans to file for marketing approval in 2015.

Nivolumab (Opdivo), when combined with platinum-based doublet chemotherapy, showed clinical efficacy similar to nivolumab monotherapy in patients with advanced refractory non–small-cell lung cancer (NSCLC), according to data from the Checkmate-012 study, although researchers cautioned that more study is needed. The FDA has granted breakthrough status to the Bristol-Myers Squibb drug and aims to review its biologics license application by the end of next March.

Patients with epidermal growth factor receptor (EGFR) mutation-positive NSCLC who continue therapy with gefitinib (Iressa) after acquiring resistance to the tyrosine kinase inhibitor receive no further clinical benefit, according to results from the IMPRESS trial. IMPRESS included 265 patients with locally advanced or metastatic NSCLC with an activating EGFR mutation and prior progression on first-line gefitinib.

Amgen’s trebananib with paclitaxel failed to demonstrate a statistically significant improvement in overall survival vs. paclitaxel with placebo in a trial involving women with recurrent platinum-resistant ovarian cancer. Median OS in the TRINOVA-1 study was 19.3 months in the trebananib arm, compared with 18.3 months in the control arm.

Have you heard?

The American Society of Clinical Oncology has endorsed a practice guideline garnered from several professional associations to guide physician decisions on when to offer molecular testing for EGFR and anaplastic lymphoma kinase mutations in patients with NSCLC.

A research team at Harvard Medical School found that only 14% of patients with newly diagnosed lung or colorectal cancer have discussed clinical trial participation with their physicians, and even fewer participate. Among patients treated with chemotherapy for advanced cancer, the discussion rate was only 25.7%. Younger age, higher education and income levels, and advanced disease were associated with a higher likelihood of having discussed clinical trial participation.

Another study, from researchers at the University of Michigan Comprehensive Cancer Center, found that nearly two thirds of colorectal cancer patients report a financial burden stemming from their treatment. Burden was greatest among patients who received chemotherapy and young patients who work in low-paying jobs.

All clinical studies mentioned in this article are phase 3 unless otherwise stated.

Spotlight on European Society for Medical Oncology

“Precision Medicine in Cancer Care” was the theme of this year’s ESMO 2014 Congress, held September 26–30 in Madrid, Spain. Among the highlights:

CLEOPATRA study results showed that first-line treatment with pertuzumab (Perjeta), trastuzumab (Herceptin), and docetaxel provided a 15.7-month increase in median overall survival (OS) values in patients with HER2-positive metastatic breast cancer, compared with placebo, trastuzumab, and docetaxel. The median OS of almost five years was the longest observed to date.

Trastuzumab offers a better outcome, defined as fewer “disease events,” than lapatinib (Tykerb), according to a new analysis of ALTTO trial results. ALTTO, the world’s largest study of the two treatments for this cancer, enrolled 8,381 participants at 946 medical centers in 44 countries.

Compared with chemotherapy, afatinib (Gilotrif), a once-daily irreversible ErbB blocker, significantly delayed tumor growth in patients with recurrent and/or head-and-neck squamous cell cancer who failed previous treatment. The LUX-Head & Neck 1 study of 483 patients in 19 countries showed that the relative risk for disease progression in patients given afatinib was 20% lower than in those given chemotherapy.

Preliminary data from the CheckMate-037 trial show that nivolumab (Opdivo), a PD-1 inhibitor, achieved superior and longer duration of response than standard chemotherapy in patients with advanced melanoma who were previously treated with ipilimumab (Yervoy).

Selected FDA approvals of biologics and specialty drugs, Sept. 16–Nov. 4, 2014
New marketing approvals and new indications
Date (type) Manufacturer Drug/trade name; administration Indication Notes
Oct. 10, 2014 (NDA) Gilead Sciences ledipasvir and sofosbuvir (Harvoni); oral Chronic hepatitis C genotype 1 infection in adults Sovaldi combo is first interferon- and ribavirin-free regimen and first once-daily combination pill for HCV genotype 1. Cure rates of 94%–99% in three phase 3 trials. $94,500 cost is equivalent to that of Sovaldi with interferon and ribavirin.
Oct. 15, 2014 (NDA) InterMune/Genentech pirfenidone (Esbriet); oral Idiopathic pulmonary fibrosis FDA-designated “breakthrough” pyridone approved after Intermune conducted a new phase 3 trial in response to a 2010 CRL. New trial demonstrated a clinically meaningful effect on forced vital capacity.
Oct. 15, 2014 (NDA) Boehringer Ingelheim nintedanib (Ofev); oral Idiopathic pulmonary fibrosis FDA-designated “breakthrough” kinase inhibitor approved on basis of one phase 2 trial and two phase 3 studies showing 45%–68% reductions in forced vital capacity, relative to placebo.
Oct. 23, 2014 (BLA) Baxter Healthcare Antihemophilic factor [recombinant], porcine sequence (Obizur) Acquired hemophilia A (acquired Factor VIII deficiency) in adults Obizur previously had received orphan drug status.
BLA=biologics license application, CRL=complete response letter, HCV=hepatitis C virus, NDA=new drug application.
Sources: American Society of Clinical Oncology, FDA, FierceBiotech, New York Times, Seeking Alpha, the Wall Street Journal, manufacturers’ news releases, and product labeling