Update for July 6, 2022

AMX0035 (Sodium phenylbutyrate & Taurursodiol)

• Sodium phenylbutyrate/taurursodiol (AMX0035) is available through an Expanded Access Program (NCT05286372). Sodium phenylbutyrate is a fatty acid used for the treatment of chronic management of patients with urea cycle disorders. Taurursodiol is also known as tauroursodeoxycholic acid and is a naturally occurring bile acid used to treat chronic cholestatic liver diseases and gallstones. AMX0035 is used to treat Amyotrophic Lateral Sclerosis (ALS) due to an ability to mitigate endoplasmic reticulum stress and mitochondrial dysfunction. Sodium phenylbutyrate reduces toxicity from endoplasmic reticulum stress. Taurursodiol protects neurons through reduction of mitochondrial bioenergetic deficits.
• In a draft report, ICER found evidence to support efficacy for AMX0035 in the treatment of amyotrophic lateral sclerosis (ALS) to be comparable or better compared to standard of care alone. If AMX0035 is priced similar to intravenous edaravone at $171,000 a year, the drug would exceed cost effectiveness thresholds.
• Canada approved AMX0035 to teat ALS in June 2022.​
• The FDA’s Peripheral and Central Nervous System Drugs Advisory Committee (PCNSDAC) voted 6-4 to reject AMX0035 in March 2022 and recommended an additional trial to evaluate efficacy. The FDA extended the PDUFA date by three months to 9/29/2022. The PCNSDAC will meet for a second time in 2022 to discuss Amylyx’s combination of sodium phenylbutyrate and taurursodiol for the treatment of ALS on 9/7/2022.

The FDA accepted the NDA for palovarotene to treat fibrodysplasia ossificans progressiva and set a PDUFA date for 12/29/2022.
 
Santhera has worldwide marketing rights for vamorolone for DMD and all other indications. Santhera began a rolling NDA for vamorolone in the treatment of DMD in March 2022. The contract manufacturer for vamorolone, will not be ready for an FDA inspection until 4Q22, so completion of the NDA will not be until the end of the year.
 
The FDA extended the PDUFA for teplizumab by three-months to allow more time to review labeling and if any post-marketing requirements are required. The new PDUFA date is 11/17/2022. 
 
The FDA put a hold on HIV trials using injectable lenacapavir due to concerns regarding the compatibility of vials made of borosilicate glass with lenacapavir solution. These vials could potentially lead to the formation of sub-visible glass particles. The FDA rejected the NDA for lenacapavir in March 2022 due to the problems with the vials. Gilead developed a new type of vial and the hold was lifted in May 2022. Gilead resubmitted an NDA for lenacapavir for the treatment of multi-drug resistant HIV-1 infection in June 2022. The new NDA includes data to demonstrate the compatibility of lenacapavir with an alternative vial type made from aluminosilicate glass.
 
The FDA rejected tebipenem for the treatment of complicated urinary tract infections and requested an addition clinical trial.
 
The EMA approved olipudase alfa to treat non-Central Nervous System manifestations of Acid Sphingomyelinase Deficiency.
 
Announced Research Updates
 
MeiraGTx, announced that in a 6-month, 45 patient, open-label, dose-escalation, Phase I/II trial, treatment with botaretigene sparoparvovec resulted in an improvement in low light visual mobility, patient reported outcomes in extreme light and ETDRS visual acuity in patients with X-linked retinitis pigmentosa (XLRP).
 
Jazz Pharmaceuticals announced that in the 51-week, 68 patient, Phase III, RELEASE MSS1 trial, treatment with nabiximols oromucosal spray did not improve the Lower Limb Muscle Tone-6 (LLMT-6) score compared to placebo in patients with multiple sclerosis spasticity.
 
Capricor announced that in an extension of the HOPE-2 trial, DMD patients received no treatment for 392 days, then were reinitiated on CAP-1002 every three months. After one-year of open label treatment, CAP-1002 continued to demonstrate improvements in the mid-level elbow PUL 1.2 score compared to placebo.
 
Novartis announced that in the 649 patient, Phase III, RATIONALE 306 trial, treatment with tislelizumab plus chemotherapy resulted in overall survival of 17.2 months compared to 10.6 months with chemotherapy alone in patients with advanced or metastatic esophageal squamous cell carcinoma. 
 
Can-Fite BioPharma announced that in the 16-week, 528 patient, Phase III, COMFORT trial, 9.7% of patients treated with piclidenoson 3 mg achieved PASI-75 compared to 2.6% with placebo in patients with moderate-to-severe plaque psoriasis. A non-inferior difference was found in a secondary endpoint at week 32, 17% of patients treated with piclidenoson achieved PASI-75 compared to 26.2% with apremilast.
 
DBV Technologies announced that in the 12-month, 362 patient, Phase III, EPITOP trial, 67% of patients who received Viaskin Peanut patch tolerated a peanut protein challenge compared to 33.5% with placebo in patients 1 to 3 years old with peanut allergies.
 
Published Research Updates
 
In the 152 patient, Phase II APPROVE trial, treatment with apatinib plus pegylated liposomal doxorubicin resulted in PFS of 5.8 months compared to 3.3 months with pegylated liposomal doxorubicin alone in patients with platinum-resistant or refractory ovarian cancer.