Update for May 4, 2022

Regulatory Update
 
The FDA approved mavacamten (Camzyos, Bristol Myers Squibb), on 4/29/2022, to improve functional capacity and symptoms in adults with symptomatic New York Heart Association (NYHA) class II to III obstructive hypertrophic cardiomyopathy. 

• Mavacamten was approved with a boxed warning regarding the risk for heart failure. Because of the risk for heart failure, mavacamten will only be available through the Camzyos Risk Evaluation and Mitigation Strategy (REMS) Program. The FDA had delayed the original PDUFA date for mavacamten, by three months in order to have more time to review the proposed REMS program that addresses the increased risk of atrial fibrillation, stroke, heart failure and sudden cardiac death.

• Use of mavacamten is contraindicated with moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers because of an increasedrisk for heart failure due to systolic dysfunction.

• BMS has set WAC for mavacamten at $89,000 per year. This is much higher than ICER’s estimated health-benefit price benchmark. ICER found the evidence of a health benefit for adding mavacamten to optimal treatment of heart failure promising but inconclusive compared to optimal therapy alone or adding the drug to disopyramide. Some concern was expressed for the long-term effects of reduction in left ventricular ejection fraction  and myocardial thickness. ICER estimated a health-benefit price benchmark (HBPB) of $12,000-$15,000. Myectomy and septal ablation were also found to be more cost effective than mavacamten.

The FDA approved oteseconazole (Vivjoa, Mycovia), on 4/28/2022, for the prevention of recurrent yeast infections in females who are not of reproductive potential.
 
The FDA rejected Hutchmed’s surufatinib for the treatment of advanced pancreatic and extrapancreatic neuroendocrine tumors and recommended a multiregional trial using a population that is similar to the U.S. population.
 
The FDA rejected Junshi’s and Coherus’ toripalimab, in combination with gemcitabine and cisplatin, for the treatment of nasopharyngeal carcinoma and recommended a change in a manufacturing quality process.
 
In December 2021, the FDA placed a hold on Pfizer’s fordadistrogene movaparvovec trials after the death of patient in a Phase Ib trial. The FDA allowed the trial to resume in April 2022.
 
Sage and Biogen initiated a rolling NDA for zuranolone for the treatment of major depressive disorder.
 
CHMP recommended approval of Amryt Pharma’s oleogel-S10 for the treatment of dystrophic and junctional epidermolysis bullosa. The FDA rejected oleogel-S10 in February 2022.
 
Brickell sold marketing and development rights for sofpironium to Botanix Pharmaceuticals.
 
Announced Research Updates
 
Lilly announced that in the 72-week, 2,539 patient, Phase III, SURMOUNT-1 trial, adding tirzepatide to a reduced-calorie diet and increased physical activity resulted in a 16% weight loss with 5 mg, 21.4% with 10 mg and 22.5% with 15 mg compared to 2.4% reduction with placebo plus diet and increased activity in adults without type 2 diabetes who have obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease. At least a 5% reduction in body weight was achieved with tirzepatide in 89% with 5 mg and 96% with 10 mg and 15 mg compared to 28% with placebo.
 
Novartis announced that in the 649 patient, Phase III, RATIONALE 306 trial, adding tislelizumab to chemotherapy improved overall survival compared to chemotherapy only in patients with advanced or metastatic esophageal squamous cell carcinoma.
 
Novo announced that in the 26-week, 526 patent, Phase IIIa, ONWARDS 2 trial, once-weekly insulin icodec lowered HbA1c 0.93% compared to a 0.71% decrease with once-daily insulin degludec in patients with type 2 diabetes switching from daily insulin. 
 
Stealth announced that in the 48-week, 176 patient, Phase II, ReCLAIM-2 trial, treatment with elamipretide did not improve low luminance visual acuity nor geographic atrophy progression compared to placebo in patients with geographic atrophy secondary to dry age-related macular degeneration.
 
Milestone announced that in the 169 patient. Phase III NODE-302 trial, a long term extension of  the 431 patient, NODE-301 trial, 105 patients experienced 188 PSVT episodes with a conversion rate of 60.2% and a median time to conversion of 15.5 minutes with self-administered nasal etripam.
 
In a 12-week, 302 patient, Phase III trial, treatment with CNTX-4975 did not reduce the Weekly Pain With Walking score in the index knee compared to placebo in patients with moderate-to-severe osteoarthritis knee pain. The results have not been announced, presented or published and are only available on clinicaltrials.gov
 
Published Research Updates
 
In the 52-week, 36 patient, Phase II/III, ASCEND trial, compared to placebo, treatment with olipudase resulted in an improvement in DLco (22% vs 3.0%), spleen volume (39% decrease vs 0.5% increase) and decrease in liver volume (28% vs 1.5%) in adult patients with acid sphingomyelinase deficiency (Niemann-Pick Disease). However, treatment with olipudase did not improve the Splenomegaly Related Score compared to placebo. 
 
In an interim analysis of a 1,153 patient, Phase IIb trial, vaccination with RSVpreF elicited an antibody response with transplacental transfer in pregnant women and their infants.
 
In a ten patient, open-label, Phase II trial, treatment with clazakizumab for at least 2.5 years stabilized eGFR at 41.6 ml/min per 1.73 m(2) at 12 months and 38.1 ml/min per 1.73 m(2) at 24 months in kidney transplant patients with chronic active antibody-mediated rejection.