GENETIC DISORDER

New drug approved for rare enzyme deficiency

The FDA has approved olipudase alfa (XENPOZYME, Sanofi) for I.V. infusion in pediatric and adult patients with acid sphingomyelinase deficiency (ASMD).

ASMD is a rare genetic disease resulting from a lack of an enzyme that breaks down the complex lipid sphingomyelin. When not broken down, sphingomyelin accumulates in the liver, spleen, lungs, and brain. The disorder usually results in early death. Olipudase alfa replaces this missing enzyme.

Results from a randomized, double-blind, placebo-controlled study of 36 patients formed the basis of the FDA's approval. Thirty-six patients with ASMD were randomized 1:1 to receive olipudase alfa or placebo I.V. every 2 weeks with intrapatient dose escalation. Primary endpoints of the trial included the percent change from baseline to week 52 in the percent predicted diffusing capacity of the lung for carbon monoxide (DLCO) and spleen volume, combined with the splenomegaly-related score in the US.

Olipudase alfa reportedly returned the least square mean percent change from baseline to week 52 compared with placebo in the predicted DLCO and spleen volume. The spenomegaly-related score decreased in both groups.

No treatment-related serious adverse events were reported, and no patients discontinued use due to an adverse-related event.

References:

U.S. Food and Drug Administration. FDA approves first treatment for acid sphingomyelinase deficiency, a rare genetic disease. 2022. http://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-. Accessed September 7, 2022.

Wasserstein M, Lachmann R, Hollak C, et al A randomized, placebo-controlled clinical trial evaluating OLIPUDASE ALFA enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults: one-year results. Genet Med. 2022;24(7):1425-1436. doi:10.1016/j.gim.2022.03.021.

PSORIASIS

New treatment for generalized pustular psoriasis

Spesolimab-sbzo (SPEVIGO, Boehringer Ingelheim [Pharmaceuticals]) has been approved by the FDA for the treatment of generalized pustular psoriasis (GPP) flares in adults.

Spesolimab is the first treatment option for the disorder and is a selective interleukin-36 receptor antagonist. Interleukin-36 is a key component of a signaling pathway in the immune system.

Approval was based on the results of a phase 2 clinical trial that showed a higher incidence of lesion clearance at week 1 than placebo.

Patients were randomly assigned 2:1 to receive either a single 900 mg I.V. dose of spesolimab or a placebo. Out of the 53 patients enrolled, 35 were to receive spesolimab and 18 were to receive a placebo. Both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, or both and were followed to week 12.

The primary endpoint of the study was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (range, 0 [no visible pustules] to 4 [severe pustulation]) at the end of week 1. A key secondary endpoint was a GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1.

At baseline, 46% of patients in the spesolimab group and 39% in the placebo group had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4.

At the end of week 1, 54% (19) in the spesolimab group had a pustulation subscore of 0, compared with 6% (1) in the placebo group; 43% (15) in the spesolimab group had a GPPGA total score of 0 or 1, compared with 11% (2) in the placebo group. Drug reactions were reported in two patients from the spesolimab group.

Infections at the end of week 1 were reported in 17% (6) in the spesolimab group. Infections were reported in 47% (24 of 51) of anyone who received spesolimab throughout the trial at week 12. Antidrug antibodies were detected in 46% (23 of 50 patients) who received at least one dose of spesolimab.

The researchers say that longer and larger trials are warranted.

References:

Boehringer. FDA approves the first treatment option for generalized pustular psoriasis flares in adults. 2022. http://www.boehringer-ingelheim.us/press-release/fda-approves-first-treatment-op. Accessed September 7, 2022.

Bachelez H, Choon S-E, Marrakchi S, et al Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021;385(26):2431-2440. doi:10.1056/nejmoa2111563.

OPIOIDS

Prescriptions decreased between 2012 and 2019

The proportion of adults in the US receiving opioids for chronic noncancer pain (CNCP) and cancer declined between 2012 and 2019, according to a study published in PLOS ONE.

The reductions in opioid prescriptions also outpaced increases in nonopioid alternatives.

Researchers examined administrative claims data from IBM MarketScan Research Databases to identify privately insured adults who were continuously enrolled in insurance for at least one calendar year from 2012 to 2019. From these individuals, they formed two groups: those with a CNCP diagnosis, such as arthritis, headache, low back pain, or neuropathic pain; and individuals with a cancer diagnosis in a calendar year.

Outcomes of the examination of records included receipt of any opioid, nonopioid medication, or nonpharmacologic CNCP therapy and opioid prescribing volume, the morphine milligrams equivalent (MME)-per-day, and days' supply. Estimates were regression-adjusted for age, sex, and region.

Over the period studied, the proportion of patients receiving opioids for CNCP decreased from 49.7% to 30.5%, and for cancer from 86.0% to 78.7%. Receipt of nonopioid pain medication remained steady for those with CNCP and increased for those with cancer from 74.4% to 78.8%. Nonpharmacologic therapy use rose among those with CNCP from 62.4% to 66.1%.

The receipt of at least one prescription with more than 90 MME-per-day decreased in those with CNCP from 13.9% to 4.9%, and in those with cancer from 26.2% to 7.6%. A supply greater than 1 week declined from 56.3% to 30.7% in those with CNCP and from 47.5% to 22.7% in those with cancer. The average number of opioid prescriptions declined from 5.2 to 3.9 in those with CNCP, and from 4.0 to 2.7 in those with cancer. Lastly, the mean MME-per-day decreased from 49.9 to 38.0 in those with CNCP, and from 62.4 to 44.7 in those with cancer.

Reference:

Bandara S, Bicket MC, McGinty EE. Trends in opioid and non-opioid treatment for chronic non-cancer pain and cancer pain among privately insured adults in the United States, 2012-2019. PLoS One. 2022;17(8). doi:10.1371/journal.pone.0272142.

DUAL ANTIPLATELET THERAPY

Two-drug strategy confers benefits and risks

Adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure, but also a significantly increased risk of clinically important bleeding, among patients undergoing coronary artery bypass graft surgery, according to an analysis published in JAMA.

Researchers analyzed randomized clinical trials (RCTs) comparing the effects of ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy versus aspirin on saphenous vein graft failure.

The primary outcome was the incidence of saphenous vein graft failure per graft in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes included: saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin.

All four RCTs were included in the meta-analysis. There were 1,316 patients and 1,668 saphenous vein grafts. Eight hundred seventy-one patients were included in the primary analysis: 435 who received ticagrelor DAPT, and 436 who received aspirin.

Ticagrelor DAPT returned a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than aspirin and was associated with a significantly lower incidence of saphenous vein graft failure per patient. Ticagrelor DAPT was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than aspirin.

Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure or BARC type 2, 3, or 5 bleeding events, according to the researchers.

Reference:

Sandner S, Redfors B, Angiolillo DJ, et al Association of dual antiplatelet therapy with ticagrelor with vein graft failure after coronary artery bypass graft surgery. JAMA. 2022;328(6):554-562. doi:10.1001/jama.2022.11966.

COVID-19 PNEUMONIA

Nitric oxide may help patients who are pregnant

Inhaled nitric oxide (iNO)₂₀₀ in patients who were pregnant with severe bilateral COVID-19 pneumonia was associated with a reduced need for oxygen supplementation and shorter hospital stays.

The results of the study were published in Obstetrics & Gynecology.

Researchers collected retrospective cohort data from patients who were pregnant and hospitalized with severe bilateral COVID-19 pneumonia at four teaching hospitals between March 2020 and December 2021. Two cohorts were formed, one of those receiving standard of care alone (SoC cohort) and those receiving iNO₂₀₀ for 30 minutes twice daily in addition to standard of care alone (iNO₂₀₀ cohort). iNO₂₀₀ was only offered at one hospital.

The prescribed primary outcome of the study was the number of days free from any oxygen supplementation at 28 days postadmission. Secondary outcomes were the hospital length of stay, rate of intubation, and ICU length of stay. Multivariable-adjusted regression analyses accounted for age, body mass index, gestational age, use of steroids, remdesivir, and the study center.

A total of 71 patients were included in the study, 51 in the SoC cohort and 20 in the iNO₂₀₀ cohort. Those receiving iNO₂₀₀ had more oxygen supplementation-free days than in the SoC cohort. According to the multivariate-adjusted analyses, iNO₂₀₀ was associated with 63.2% more days free from oxygen supplementation, a 59.7% shorter ICU length of stay, and a 63.6% shorter hospital length of stay. No iNO₂₀₀-related adverse events were reported.

Reference:

Valsecchi C, Winterton D, Safaee Fakhr B, et al High-dose inhaled nitric oxide for the treatment of spontaneously breathing pregnant patients with severe coronavirus disease 2019 (COVID-19) pneumonia. Obstet Gynecol. 2022;140(2):195-203. doi:10.1097/aog.0000000000004847.