Novitium's Generic Sildenafil for PAH Treatment Approved by FDA - Pulmonary Hypertension News

Novitium's Generic Sildenafil for PAH Treatment Approved by FDA - Pulmonary Hypertension News

Novitium's Generic Sildenafil for PAH Treatment Approved by FDA - Pulmonary Hypertension News

Posted: 12 Jun 2019 05:00 AM PDT

The U.S. Food and Drug Administration (FDA) has approved Novitium Pharma's generic sildenafil for oral suspension at a dose of 10 mg/mL for the treatment of pulmonary arterial hypertension (PAH).

This product, which had been designated a competitive generic therapy by the FDA, is the first approved generic equivalent to Pfizer's Revatio, a vasodilator agent that induces blood vessel widening and relaxation to help patients breathe better.

Revatio was approved in 2005 by the FDA for the treatment of PAH, specifically for those patients classified in the World Health organization (WHO) Group 1.

"We are pleased to announce that the launch of sildenafil for oral suspension has already initiated," Chad Gassert, CEO of Novitium, said in a press release. "Novitium remains dedicated to providing patients with a steady supply of affordable treatment options, and to progressing the availability of generics in niche therapeutic categories."

Novitium had submitted an abbreviated new drug application (ANDA) for the compound, which is filed for generic medications seeking FDA approval. Once approved, the company earns the rights to manufacture and market the therapy as an equally safe, effective, and less expensive alternative to the brand-name product — in this case, Revatio.

The FDA can attribute the competitive generic therapy designation to any medication for which they determine there is inadequate generic competition, or in other words, that there is not more than one approved therapy in the active section of the FDA's Orange Book. Medicines receiving this designation are eligible for accelerated development and review of their ANDA application.

Revatio is currently included on the FDA's drug shortages list, which includes those whose market requirements are not being met, either due to delays in the manufacturing process or due to excessive market demand. The FDA works closely with drug manufacturers to prevent or reduce the impact of shortages in treatments.

According to Novitium, a pharmaceutical company based in the U.S. that specializes in the development and marketing of generic therapies, sildenafil is its third generic product that has received the designation of competitive generic therapy, and the seventh whose ANDA has been approved this year.

Growing Doubt, Uncertainty Over PDE5i Use in Left Heart Disease - Medscape

Posted: 12 Jun 2019 11:22 AM PDT

A new INTERMACS study calls into question the off-label use of preoperative phosphodiesterase-5 inhibitors (PDE5i) to reduce the risk for right heart failure (RHF) in patients receiving a left ventricular assist device (LVAD).

LVAD recipients treated with preoperative PDE5i therapy were more likely than control subjects to experience severe early RHF in unadjusted (29.4% vs 23.1%) and propensity-matched (odds ratio, 1.31; 95% CI, 1.09 - 1.57) analyses.

Major bleeding events were also significantly higher in those on a PDEF5i, according to the study, published June 11 in Circulation: Heart Failure.

"Our research didn't demonstrate a signal of benefit and, in fact, suggested even a signal of potential harm, and thus really indicates the need for well-done prospective research looking at the role of the medication in this population," senior author Michael Kiernan, MD, MS, Tufts Medical Center, Boston, told theheart.org | Medscape Cardiology.

Although PDE5 inhibitors are known to be an effective therapy for primary pulmonary arterial hypertension, evidence is thin to support off-label use to reduce right ventricular (RV) afterload before LVAD implantation.

"It's something that I am increasingly looking at askance," Brian A. Houston, MD, director of mechanical circulatory support, Medical University of South Carolina, Charleston, told theheart.org | Medscape Cardiology. "Previously, we've leaned on small trials with surrogate outcomes or, even more vexingly, on biological plausibility to say it makes sense that if you give someone a pulmonary vasodilator, the RV afterload is reduced and they'll do better."

"But this study, even though it's retrospective and all the caveats of that, certainly calls into doubt the strength of that argument," he said. "And then, when you couple that with the SIOVAC trial," in which patients had worse outcomes when treated with sildenafil after valve repair or replacement, "it certainly calls into question whether we should be using these therapies in patients with left heart disease, which includes our LVAD patients."

In the absence of good alternative therapies, however, the temptation is strong. One in 10 patients (1199; 10.3%) were on preoperative PDE5i therapy in the study involving 11,544 participants with a first-time LVAD surgery in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), a representative cross section of LVADs implanted in North America.

Patients on PDE5i therapy had more severe INTERMACS profiles, higher use of renal replacement therapy, and higher mean pulmonary artery pressures (35.2 vs 33.0 mm Hg) and pulmonary vascular resistance values (2.6 vs 2.3 WU).

The primary end point of severe early RHF — defined as death from RHF within 30 days, need for right ventricular assist device (RVAD) within 30 days, or use of inotropes beyond 14 days — occurred in 23.7% of patients overall.

The association between severe early RHF and PDE5i use after propensity matching for 22 variables was driven by a higher incidence of prolonged inotrope support (24.0% vs 19.9%; P = .009). There were no significant differences between groups in RVAD use, death from RHF, or in 3- and 6-month quality of life and 6-minute walk distances, the authors report.

The PDE5i group had more major bleeding events than control subjects during the first month after LVAD implantation (24.5% vs 17.9%; hazard ratio [HR], 1.20; 95% CI, 1.06 - 1.36) that concentrated in the immediate postoperative period. A landmark analysis confirmed a significantly higher major bleeding event rate at 7 days with preoperative PDE5i use (HR, 1.52; 95% CI, 1.15 - 2.00), but similar rates thereafter.

Houston noted that PDE5 inhibitors can have a strong effect on platelet function that is often underappreciated going into surgery. He suggested that the 52% increased risk of bleeding may explain the signal for longer inotrope support because patients who bleed more get more volume resuscitation, the RV's going to be volume loaded, and inotropes won't be pulled off as quickly. After all that settles down, however, the patient will probably do okay.

"So it may be that explains the signal for longer inotrope use but not more mortality or morbidity, and that's really interesting because that would change practice for sure," he said. "You'd make sure to get patients off their PDE5 inhibitors before their operation. And I think that's an interesting hypothesis to draw from this study."

"It's certainly a reasonable explanation for what may have occurred in these patients," observed Kiernan. "But the converse is that it could be purely a reflection of the patients underlying substrate."

Subgroup analyses failed to identify a signal of benefit for preoperative PDE5i among patients stratified by markers of pulmonary hypertension or right heart dysfunction. The sole exception was among patients in the middle tertile of pulmonary artery systolic pressure, who had a higher frequency of early severe RHF.

"The call to action as presented by this study is increasingly pressing — if pulmonary arterial hypertension-specific therapy is indeed shown to increase the risk of harm to our patients with LVAD or LHD, guidelines and practice patterns should expeditiously abandon the arguments of biological plausibility and surrogate end points just as they did with antiarrhythmic agents for premature ventricular contractions and inotropic medications for LV failure," Houston writes in an accompanying editorial.

Limitations of the retrospective analysis are the potential for residual unmeasured confounders, missing pulmonary arterial wedge pressure values in 30% of cases, and a lack of information on the indication for preoperative PDE5i therapy, timing of its initiation in relation to LVAD implant, and whether it was continued in the 30 days after surgery.

Both Kiernan and Houston noted that the ongoing SOPRANO trial of macitentan may shed light on the utility of endothelin receptor antagonist therapy after LVAD. In the recent MELODY-1 study, however, macitentan failed to improve pulmonary vascular resistance and was associated with numerically more adverse events in patients with pulmonary hypertension due to left heart disease.

Kiernan reports consulting fees from Medtronic and travel support from Abbott. Coauthor disclosures are listed in the paper. Houston reports no relevant disclosures.

Circ Heart Fail. Published online June 11, 2019. Full text, Editorial

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, join us on Twitter and Facebook.

AnMed Health gains national recognition through the Pulmonary Hypertension Association - WSPA.com

Posted: 22 May 2019 12:00 AM PDT

ANDERSON, S.C. (WSPA) — Wednesday, AnMed Health earned an accreditation from the Pulmonary Hypertension Association for specialized treatment of patients with pulmonary arterial hypertension.

 AnMed is one of only six accredited Regional Clinical Care Centers across the nation. The hospital is also the first, and currently the only, hospital in South Carolina with this award.

Dr Abhijit Raval, AnMed's Director of Interventional Pulmonary & Pulmonary Vascular Disease, says Pulmonary Arterial Hypertension is easily misdiagnosed.

The disease does not have a singular known cause and some of the symptoms do match other diseases.

While the disease has no cure, there are 14 different medications, and physical therapies that drastically improve the patients quality of life. 

Tina Lisenby had been misdiagnosed for several years, but she said everything changed for the better when Dr Raval diagnosed her in 2009.

"I can do-have a great life. I have to learn to pace myself. On the days when I'm not feeling quite as well. I just have to learn to take my time. Rest when I need to. And try to do more the next day," Lisenby said. 

Dr. Raval noted several years on the study of Pulmonary Arterial Hypertension helps him to accurately diagnose patients, which earned the hospital the coveted accreditation. 

"What it brings is more resources. What it brings is more structure to us. It brings us more patients that we can treat more effectively. It kind of broadens our horizons, where we can reach out to the other communities and take care of their patients as well," Dr. Raval said. 

Both Dr. Raval and Lisenby said its best to check with your physician if shortness of breath, dizzy spells, and numbness become a continuous problem.

It's best to ask your physical about all the possibilities when it comes to your health. 

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