Updates on Idelalisib, A New Treatment for Acquired Hemophilia A, and More

DEA Places New Restrictions on Vicodin and other Pain Medicines

Effective October 6, 2014, the US Food and Drug Administration rescheduled hydrocodone combination products (HCPs) from schedule III to schedule II controlled substances. This action means that HCPs, such as vicodin, will have tighter restrictions on access. Patients must present a written prescription to receive the drug; in most instances, doctors will no longer be able to call in a prescription to the pharmacy. Prescription refills are prohibited, but at his or her discretion, a doctor can issue multiple prescriptions that would provide up to a 90-day supply. Many patients take HCPs to manage pain associated with chronic disease, including cancer.

Source: US DEA Federal Register. 2014;79(163):49661-82.

FDA Approves First Oral Treatment for Gaucher Disease

Eliglustat (Cerdelga™; Genzyme) was recently approved for the long-term treatment of patients with the Type 1 form of Gaucher disease, a rare genetic disorder with multiple hematologic manifestations. Eliglustat is taken orally, in capsule form. The drug works by slowing down the production of the fatty materials that collect in the spleen, liver, and bone marrow of patients with Gaucher disease. The safety and effectiveness of Cerdelga were evaluated in two clinical trials: one examined patients who had not previously received enzyme replacement therapy, and the other compared Cerdelga and enzyme replacement therapy in previously treated patients. In the first study, treatment with Cerdelga resulted in a greater reduction in spleen volume, liver volume, blood platelet count, and red blood cell level – compared to placebo. In the second trial, Cerdelga resulted in similar stabilization of hemoglobin level, platelet count, and spleen and liver volume as the enzyme replacement therapy imiglucerase. The most commonly observed side effects with Cerdelga were fatigue, headache, nausea, diarrhea, back pain, pain in extremities, and upper abdominal pain.

Source: FDA News Release

Google Searches for Cancer and Heart Attack Detector

The Google X research lab has set its sights on designing tiny magnetic particles to patrol the human body for signs of cancers and other diseases. The announcement was made at The Wall Street Journal’s WSJD Live conference. At less than one-thousandth the width of a red blood cell, these nanoparticles would seek out and attach themselves to cells, proteins, or other molecules inside the body. The company also is working on a wearable device with a magnet to attract and count the particles, as a monitoring tool.

The goal is to provide an early warning system for cancer and other diseases, and, according to Andrew Conrad, PhD, head of the Life Sciences team at the Google X research lab, the dream is to have “every test you ever go to the doctor for done through this system.” The reality, though, is more than five years off, industry experts say.

Questions about how the nanoparticles will be delivered, as well as regulatory issues, remain. To those concerned about patient information security, Dr. Conrad said Google will not collect or store medical data itself. Instead, Google plans to license the technology to others who will handle the information and its security. 

Source: The Wall Street Journal, October 29, 2014

Pivotal Phase 3 VALOR Trial Fails to Meet Its Primary Endpoint

VALOR is a phase 3, randomized, double-blind, placebo-controlled, trial comparing cytarabine with or without vosaroxin, the study agent, in 711 patients with relapsed or refractory acute myeloid leukemia (AML). The trial did not meet its primary endpoint (statistically significant improvement in overall survival), with a median overall survival of 7.5 months for vosaroxin and cytarabine – compared to 6.1 months for placebo and cytarabine (HR=0.865; P=0.06). When an analysis of overall survival was censored for stem cell transplantation, however, vosaroxin resulted in better median overall survival than placebo and cytarabine (6.7 months vs. 5.3 months [HR=0.809; P=0.02]). The trial also demonstrated a clinically significant benefit in complete remission rate (30.1% vs. 16.3% [P=0.0000148]), the secondary endpoint. In terms of safety, patients taking vosaroxin experienced serious adverse events more often than the placebo arm (55.5% vs. 35.7%); these results were consistent with those observed in previous company trials. Vosaroxin also has been granted “fast track” designation by the FDA for the potential treatment of relapsed or refractory AML in combination with cytarabine.

Source: Sunesis Pharmaceuticals, Inc. press release

FDA Approves New Treatment for Acquired Hemophilia A

Obizur™ (antihemophilic factor [recombinant], porcine sequence; Baxter Healthcare Corporation) was recently approved for the treatment of bleeding episodes in adults with acquired hemophilia A (acquired Factor VIII [FVIII] deficiency). This approval was based on safety and efficacy results from a clinical trial of 29 adults with acquired hemophilia A who received Obizur to treat a serious bleeding episode. The trial demonstrated treatment efficacy, and there were no safety concerns identified. Acquired hemophilia A is a rare, but potentially life-threatening, bleeding disorder caused by the development of antibodies (immune system proteins) directed against the body’s own FVIII, a protein important for blood clotting. The recombinant analogue of porcine (pig) FVIII contained in Obizur is similar enough to human FVIII to be effective in blood clotting, but is less likely to be affected by the antibodies against human FVIII that are present in people with acquired hemophilia A.

Source: FDA News Release

Slippery Coating on Medical Devices Helps Get a Handle on Blood Clots

A new bioinspired coating for medical devices repels blood and bacteria, according to results from a large animal efficacy study conducted by scientists at Harvard’s Wyss Institute for Biologically Inspired Engineering.

The coating is derived from the carnivorous plant, nepenthes, which produce a super-slippery surface that causes insects to climb into the plant and slide into the trap. Scientists tested whether this idea could be applied to the medical problem of blood clots that can occur when medical devices are implanted into the body.

Using FDA-approved materials, engineers and scientists developed a coating that repelled blood from more than 20 medically relevant substrates the team tested – made of plastic to glass and metal – and also suppressed biofilm formation (FIGURE). Results were reported in the journal Nature Biotechnology.

Blood sticks to the untreated glass slide, but not to the coated slide.

When the team implanted medical-grade tubing and catheters coated with the material in large blood vessels in pigs, it prevented blood from clotting for at least eight hours without the use of blood thinners, such as heparin and warfarin – medicines that can cause their own bleeding problems.

“Devising a way to prevent blood clotting without using anticoagulants is one of the holy grails in medicine,” said Don Ingber, MD, PhD, founding director of Harvard’s Wyss Institute. 

Source: Leslie DC, et al. A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling. Nat Biotech. 2014 October 12. [Epub ahead of print]

New Sickle Cell Disease Treatment Receives Fast Track Designation

NKTT120, a humanized monoclonal antibody that specifically deletes iNKT cells designed to treat sickle cell disease (SCD), was recently granted the FDA’s “Fast Track” designation. iNKT cells are regulatory T cells that have been demonstrated to act as key mediators of organ damage in preclinical models of SCD. Fast Track designation is intended to facilitate development and expedite review of drugs meant to treat serious or life-threatening medical conditions, as well as drugs that demonstrate the potential to address unmet medical needs. NKTT120 previously received the FDA’s “Orphan Drug” designation for the treatment of SCD. NKT Therapeutics also announced that the company has completed dosing in a Phase 1b trial of NKTT120 in patients with SCD. This trial will determine the drug’s safety, as well as its effects on markers of inflammation, daily pain scores, and Quality of Life.

Source: NKT Therapeutics, Inc. press release

ASH and the FDA Present Updates on Idelalisib for the Treatment of CLL, FL, and SLL

Earlier this year, the FDA approved idelalisib (Zydelig® tablets; Gilead Sciences, Inc.) for the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL), relapsed small lymphocytic lymphoma (SLL), and relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab. To offer hematologists/oncologists guidance in understanding how this drug fits into the treatment landscape for these conditions, ASH, in collaboration with the FDA, recently hosted a webinar explaining idelalisib’s approval.

The FDA’s approval of idelalisib for CLL was based on the results of an international, multicenter, randomized (1:1), placebo-controlled trial of 220 patients who were treated with either twice-daily idelalisib 150 mg + rituximab or placebo + rituximab. Median progression-free survival, the study’s primary efficacy endpoint, was not reached in the idelalisib arm and was 5.5 months in the placebo arm [HR = 0.18 (95% CI 0.10-0.32); P < 0.0001]. Accelerated approval for FL and SLL was granted based on the results of a multicenter, single arm, open-label trial involving 123 patients with relapsed indolent non-Hodgkin lymphomas; twice-daily idelalisib 150 mg was associated with overall response rates of 54 percent and 58 percent in patients with FL and SLL, respectively.

The most common adverse reactions with idelalisib were diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash. Idelasib carries a Boxed Warning alerting patients and health-care professionals of the following fatal and serious adverse reactions: hepatotoxicity, severe diarrhea or colitis, pneumonitis, and intestinal perforation.

So, where does idelalisib fit in the treatment landscape? Speaker Jennifer R. Brown, MD, PhD, an investigator on the phase 1 study investigating idelalisib in CLL, noted that physicians should consider the agents’ toxicity profiles when choosing between approved therapies.

“We know that in CLL, of course, ibrutinib has recently received full approval for the randomized trial comparing ibrutinib to ofatumumab,” Dr. Brown noted, “and the progression-free survival curve for that study looks fairly similar to the survival curves we saw with idelalisib and rituximab.”

 Given the toxicity profiles of each regimen, she suggested the following:

  • For patients requiring anticoagulation and those with histories of hepatitis or atrial fibrillation, use idelalisib.
  • In patients with a history of hepatitis or inflammatory bowel disease, use ibrutinib.

“Another issue concerning how we might think about sequencing these drugs to maximize overall patient benefit is that we don’t know anything yet about the mechanisms of resistance to idealisib,” Dr. Brown added. This is an area of active investigation, and as these mechanisms become clearer, ideas about optimal sequencing with idelalisib may change.

In the case of indolent lymphoma, there are fewer therapeutic choices than with CLL – mainly because there is no equivalent to ibrutinib in this setting. “The data suggest impressive activity in a very difficult patient population (patients with rituximab-refractory, chemotherapy-refractory disease),” Dr. Brown explained, “so it is likely that idelalisib may be used earlier, especially in patients who have comorbidities or who cannot tolerate chemotherapy.”

*ASH, in collaboration with the FDA, offers webinars that feature an unbiased discussion of newly approved hematology therapies. Access recordings of these programs at ASHonDemand.org.