Leading the Way in Life Science Technologies

GEN Exclusives

More »

The Lists

More »
April 17, 2017

25 Clinical Failures of Q1 2017

These Drug Candidates Missed their Primary Endpoints, With Varying Consequences

25 Clinical Failures of Q1 2017

High as the odds are for clinical success, a recent report found the overall likelihood of approval for all drug candidates that make it to Phase I is 9.6%—the cost of clinical failure is even higher.

  • OCR-002 (ornithine phenylacetate)

    Sponsor: Ocera Therapeutics

    Indication: Hepatic encephalopathy (HE)

    Type of drug: Ammonia scavenger

    How drug failed: Did not meet primary endpoint of statistically significant reduction compared with placebo in time to improvement in HE symptoms in the Phase IIb STOP-HE study, though company quickly added that OCR-002 showed a 17-hour reduction over placebo of 47 vs. 64 hours.

    Date of announcement: January 30

  • Ozanezumab (GSK1223249)

    Sponsor: GlaxoSmithKline

    Indication: Amyotrophic lateral sclerosis (ALS)

    Type of drug: Anti-Nogo-A monoclonal antibody

    How drug failed: Did not meet its primary endpoint of statistically significant improvement in the function and survival of ALS patients in the Phase II NOG112264 study compared with placebo, as measured by the joint rank scores for combined analysis of function and survival measured by the ALS Functional Rating Scale-Revised over 48-weeks. “Nogo-A does not seem to be an effective therapeutic target in ALS,” researchers concluded in The Lancet Neurology.

    Date of announcement: January 27

  • PEGPH20

    Sponsor: Halozyme Therapeutics

    Indication: Metastatic pancreatic cancer

    Type of drug: Treatment is based on company’s proprietary rHuPH20, a recombinant human hyaluronidase enzyme that temporarily degrades hyaluronan (HA), a glycosaminoglycan or chain of natural sugars that accumulate around certain tumors.

    How drug failed: During a planned early futility analysis, the independent Data Monitoring Committee of the SWOG Phase Ib/II trial concluded, based on preliminary data, that adding PEGPH20 every two weeks to modified FOLFIRINOX was unlikely to show a statistically significant improvement in the primary endpoint of overall survival compared to modified FOLFIRINOX alone. Trial was designed to compare the combination of PEGPH20 plus modified FOLFIRINOX chemotherapy, versus modified FOLFIRINOX alone, in patients with previously untreated metastatic pancreatic cancer.

    Date of announcement: March 30

  • Prophage G-200

    Sponsors: Agenus and Roche/Genentech

    Indication: Glioblastoma

    Type of drug: Heat shock protein peptide complex-96 (HSPPC-96) vaccine

    How drug failed: The company disclosed February 21 that it halted Phase II trial upon recommendation of the study’s Data and Safety Monitoring Board, which concluded that lead product candidate Prophage G-200 would be unlikely to show better overall survival in combination with Roche/Genentech’s marketed cancer drug Avastin® (bevacizumab) than Avastin alone in patients with surgically resectable recurrent glioblastoma multiforme.

    Date of announcement: February 21

  • Rocapuldencel-T (AGS-003)

    Sponsor: Argos Therapeutics

    Indication: Metastatic renal cell carcinoma (mRCC)

    Type of drug: Individualized immunotherapy designed to work by capturing mutated and variant antigens specific to a patient's tumor and inducing an immune response targeting that patient's tumor antigens.

    How drug failed: Following a planned interim data review, the Independent Data Monitoring Committee for the Phase III ADAPT trial concluded that rocapuldencel-T was likely to fail in combination with Pfizer’s Sutent® (sunitinib malate) and standard-of-care for mRCC.

    Date of announcement: February 22

  • Sapacitabine (CYC682)

    Sponsor: Cyclacel

    Indication: Acute myeloid leukemia (AML)

    Type of drug: Oral nucleoside analog prodrug

    How drug failed: Did not meet its primary endpoint of increasing overall survival in the Phase III SEAMLESS study, which compared a regimen of alternating cycles of sapacitabine and decitabine therapy with decitabine alone in AML patients aged 70 years and over who were not candidates for or refused intensive induction chemotherapy. Cyclacel said the sapacitabine regimen improved the complete remission rate, a secondary endpoint, and that a subgroup of patients demonstrating low baseline peripheral white blood cell count showed an overall survival increase.

    Date of announcement: February 23

  • Selinexor (KPT-330)

    Sponsor: Karyopharm Therapeutics

    Indication: Relapsed/Refractory Acute Myeloid Leukemia

    Type of drug: First-in-class, oral selective inhibitor of nuclear export (SINE™) compound designed to bind with and inhibit the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus

    How drug failed: Following a planned interim analysis of the Phase II SOPRA trial, the study’s independent Data Safety Monitoring Board and the company concluded that selinexor would not show statistical significance for overall survival, the study’s primary endpoint. However, Karyopharm and the board agreed that patients who showed complete response following selinexor treatment could continue on the selinexor arm or the physician’s choice arm following discussion with their physicians, since those patients showed a greater OS benefit compared to physician’s choice.

    Date of announcement: March 3

  • Serelaxin (RLX030)

    Sponsor: Novartis

    Indication: Acute heart failure (AHF)

    Type of drug: Recombinant form of the human relaxin-2 hormone

    How drug failed: Did not meet its primary endpoints in the Phase III RELAX-AHF-2 trial of a reduction in cardiovascular death through day 180, or a reduction in worsening heart failure through day 5. RELAX-AHF-2 assessed the efficacy, safety, and tolerability of serelaxin when added to standard of care in patients with AHF. Launched in 2013, the study included 6,600 patients hospitalized for AHF.

    Date of announcement: March 22

  • Tivantinib

    Sponsor: ArQule and Daiichi Sankyo

    Indication: Hepatocellular carcinoma (HCC)

    Type of drug: Oral inhibitor of the MET receptor tyrosine kinase 

    How drug failed: Did not meet its primary endpoint of improving overall survival in the Phase III METIV-HCC trial. The trial compared tivantinib to best supportive care in patients with MET-overexpressing, inoperable HCC intolerant to, or previously treated with, systemic therapy. A total of 340 patients with MET-overexpressing HCC were randomized in the trial’s intent-to-treat population.

    The following month, tivantinib did not meet its primary endpoint of progression-free survival (PFS) in the Phase III JET-HCC trial of tivantinib in Japan. Top-line results did not show a significant difference in PFS between the tivantinib group and the placebo group in JET-HCC, which enrolled approximately 190 Japanese patients with c-Met diagnostic-high inoperable HCC with a history of prior therapy with Bayer’s Nexavar® (sorafenib).

    Dates of announcement: February 17 (METIV-HCC failure), March 27 (JET-HCC failure)

  • Trabodenoson

    Sponsor: Inotek Pharmaceuticals

    Indication: Glaucoma

    Type of drug: First-in-class highly selective adenosine mimetic targeting the A1subreceptor

    How drug failed: Did not achieve primary endpoint of superior reduction in intraocular pressure (IOP) compared with placebo at all 12 time points in the Phase III MATrX-1 trial—Days 28, 42, and 84 and at four time points during each of these days: 8AM, 10AM, 12PM, and 4PM. The 8AM time point did not achieve statistical separation with any trabodenoson dose. However, the 6%/2000 mcg QD dose of trabodenoson was statistically superior to placebo at Days 84, 42, 14, and marginally superior at Day 28, where daily IOP reduction from diurnal baseline at three months was 4.25 mmHg compared to 2.38 mmHg for placebo, and 5.29 mmHg for the timolol 0.5% twice-daily control arm.

    Date of announcement: January 3

  • TRC105

    Sponsor: Tracon Pharmaceuticals

    Indication: Recurrent glioblastoma (GBM)

    Type of drug: Endoglin antibody

    How drug failed: Did not meet primary endpoint of in a Phase II clinical trial assessing combination of TRC105 and Roche/Genentech’s Avastinin® (bevacizumab) in recurrent GBM. Primary endpoint was three-month improvement in progression-free survival (PFS) from the expected value of 3.45 months with single agent Avastin. The combination did not improve median PFS vs. single agent Avastin in recurrent GBM patients, but was associated with a nonsignificant increase in OS. 

    Date of announcement: February 9

  • UX007 (triheptanoin)

    Sponsor: Ultragenyx Pharmaceutical

    Indication: Glucose transporter type-1 deficiency syndrome (Glut1 DS)

    Type of drug: Highly purified, synthetic seven-carbon fatty acid triglycerid

    How drug failed: Did not meet the primary endpoint in Phase II study of reducing the frequency of total number of observable and absence seizures among patients Glut1 DS patients with seizures who were treated from baseline to Week 8 with UX007, compared to placebo. In a prespecified secondary analysis, 19 patients with absence seizures showed a 47.3% reduction in seizure frequency after eight weeks of treatment with UX007, compared to baseline. While clinically significant, the results did not meet the trial’s statistical significance threshold of 0.005.

    Ultragenyx has licensed rights to UX007 from Baylor Research Institute and UniQuest, the main commercialization company of The University of Queensland.

    Date of announcement: March 22

  • Vapendavir

    Sponsor: Aviragen Therapeutics

    Indication: Asthma

    Type of drug: Oral capsid-binding antiviral drug

    How drug failed: Did not meet its primary endpoint in the Phase IIb SPIRITUS study evaluating the candidate in moderate-to-severe asthma patients with a rhinovirus infection. Vapendavir failed to show a statistically significant reduction in the asthma control questionnaire-6 at day 14, the primary endpoint, for either the 264 mg or 528 mg cohorts, compared to placebo.

    Date of announcement: February 13

  • Verubecestat (MK-8931)

    Sponsor: Merck & Co.

    Indication: Alzheimer’s disease

    Type of drug: Small-molecule inhibitor of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1)

    How drug failed: Company halted the pivotal Phase II/III EPOCH trial, on the recommendation of the study’s external data monitoring committee, which said that the trial had “virtually no chance of finding a positive clinical effect.” The placebo-controlled EPOCH study was investigating the efficacy of two doses of once-daily verubecestat, alongside standard of care in patients with mild-to-moderate Alzheimer’s disease.

    Date of announcement: February 14

  • XEN801

    Sponsor: Xenon Pharmaceuticals

    Indication: Moderate-to-severe facial acne

    Type of drug: Topical stearoyl Co-A desaturase-1 (SCD1) inhibitor

    How drug failed: Did not meet its primary endpoint in a Phase II trial assessing the candidate in moderate-to-severe facial acne. XEN801 did not show a statistically significant difference from vehicle placebo in its primary endpoint of the percent change in total (inflammatory and noninflammatory) lesion count from baseline to week 12, Xenon said. XEN801 also did not demonstrate statistical significance against key secondary efficacy endpoints.

    Date of announcement: March 24

Related content