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Amylyx (AMLX) had good regulatory news to trumpet on Tuesday, when it announced that the FDA’s Pe­riph­er­al and Cen­tral Ner­vous Sys­tem Drugs Ad­vi­so­ry Com­mit­tee agreed to hold a second hearing reconsidering the company’s NDA for its amyotrophic lateral sclerosis (ALS) drug AMX0035.

The rehearing is a rare one for an advisory committee. At PCNSDAC’s first hearing on AMX0035 in March, the advisory committee recommended 6-4 against agency approval of the ALS combination drug. The FDA usually follows the recommendations of its advisory committees but does not have to.

It took a couple of days, but investors eventually warmed up this week to Amylyx on news of the planned second hearing, giving the shares a 13% boost. While the shares inched up only 0.1% or 3 cents a share (from $19.47 to $19.50) the day of the announcement, that was followed by a 6% gain on Wednesday, up to $20.59, then a 7% rise yesterday, to an even $22.

After the first advisory committee hearing March 30, Amylyx shares plunged 54% from $14.93 to $6.85 on May 11, before rebounding. The company’s shares this year have closed as high as $32.90 on February 28.

“Interestingly, the stock is also moving back to the range where it traded going into the first AdCom. This whole saga has been and remains a very unusual situation, and it still ‘ain’t over,’ Marc Goodman, a Senior Research Analyst at SVB Securities covering Neuroscience and Ophthalmology, wrote Tuesday in a research note.

At the planned second hearing,discussions will focus on the additional analyses of data from the Company’s clinical studies that were determined by the FDA to constitute a major amendment to the NDA,” Amylyx stated on Tuesday—without furnishing details.

But in a conference call with analysts, Goodman reported, Amylyx shed a little more light on the additional analyses.

“Management indicated that the additional clinical analyses submitted to the FDA bolster support for AMX0035’s functional and overall survival benefit,” Goodman wrote. “It highlighted recently published analyses, including: (1) long-term pre-specified analyses published in the Journal of Neurology, Neurosurgery and Psychiatry, demonstrating that early administration of AMX0035 resulted in a lower occurrence of tracheostomy/permanent assisted ventilation (PAV) and delayed first hospitalization during the Phase 2 CENTAUR trial and follow-up period in ALS patients.”

Amylyx also cited post-hoc analyses published in Muscle & Nerve that suggested a larger survival benefit for AMX0035, adjusting for placebo crossover, that ranged from 10.6 to 18.8 months vs 6.9 months in the original pre-specified intent-to-treat population (ITT) analysis.

“While management remains cautiously optimistic, it believes that the recent publications provide strong evidence of AMX0035’s functional and survival benefit, and it is excited to have an opportunity to review the survival data in more depth in the second AdCom than time allowed for in the first AdCom,” Goodman added.

After the first hearing, the advisory committee majority concluded that data from Amylyx’s single 137-patient clinical study, the Phase II CENTAUR trial (NCT03127514), did not meet the panel’s standard for substantial evidence and persuasiveness. The majority cited the rate of decline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) 24 weeks after treatment.

However, Amylyx has insisted that its primary endpoint was met, reporting that participants treated with AMX035 scored, on average, 2.32 points higher than placebo patients on ALSFRS-R over 24 weeks. “We remain confident in the data from the Phase 2 CENTAUR trial and the potential benefits of AMX0035 as a treatment option for people living with ALS,” Jamie Timmons, MD, Amylyx’s Head of Scientific Communications, said in a company statement following the first advisory committee hearing.

The FDA review of AMX0035 is being closely watched by developers of other ALS treatments—including NeuroSense, which told GEN Edge last month it was learning from Amylyx’s interaction with the FDA advisory panel. NeuroSense has advanced its oral ALS candidate PrimeC into the Phase IIb PARADIGM trial (NCT05357950), which enrolled its first patient in June. PrimeC is a novel formulation of a fixed-dose combination drug combining the broad-spectrum fluoroquinolone antibiotic ciprofloxacin and celecoxib, a non-steroidal anti-inflammatory drug (NSAID) marketed as Celebrex® but also available as a generic.

Applied Molecular Transport (AMTI)

Shares of Applied Molecular Transport (AMT) tumbled 36% on Wednesday after the company released disappointing topline results acknowledging that its AMT-101, in combination with adalimumab (marketed by AbbVie as Humira®) did not demonstrate added clinical benefit compared to adalimumab alone at week 8 in the Phase II MARKET trial (NCT05372939), assessing the combo in patients with moderate to severe ulcerative colitis.

The clinical remission rate of 31.8% (7 of 22) seen in patients receiving the AMT-101/adalimumab combination was similar to the 33.3% (9 of 27) rate seen in patients receiving placebo plus adalimumab, AMT reported.

However, the company also cited a post hoc analysis of patients with shorter duration of ulcerative colitis (UC) of less than 5 years. That analysis showed a clinical remission rate of 43.8% (7 of 16) in patients receiving the combination versus 15.4% (2 of 13) in patients receiving adalimumab alone—“suggesting combination treatment earlier in the course of disease may be beneficial,” according to AMT.

“We did not anticipate the high rate of remission in the adalimumab alone arm,” stated Bittoo Kanwar, MD, AMT’s Chief Medical Officer. “These data will further inform our future development plans for AMT-101 in combination therapy and we plan to discuss next steps with FDA.”

AMT-101 is a novel GI-selective, oral fusion of IL-10 and AMT’s proprietary carrier molecule.

AMT said it anticipates releasing topline results from another Phase II trial of AMT-101 in UC, the ongoing LOMBARD monotherapy trial (NCT04583358) in the second half of 2022. AMT-101 is also being developed for chronic pouchitis and rheumatoid arthritis.

CytomX (CTMX)

Shares of CytomX plummeted 38% on Thursday, a day after the company said it would seek a partner to continue development of its lead candidate, its wholly owned praluzatamab ravtansine. The decision followed mixed results from a Phase II trial (NCT04596150) of the DM4-conjugated, conditionally activated antibody-drug conjugate (ADC) targeting CD166.

The trial was designed to evaluate praluzatamab ravtansine in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-non-amplified breast cancer. Praluzatamab ravtansine met its primary efficacy endpoint among 47 patients receiving 7 mg/kg every three weeks, based on a confirmed objective response rate (ORR) of 15%.

The trial’s other two arms consisted of triple negative breast cancer patients: Arm B had patients receiving 6 mg/kg or 7 mg/kg of praluzatamab ravtansine monotherapy—and showed ORR of less than 10%. As a result, enrollment will be halted in that arm as well as Arm C, where patients were dosed with 6 mg/kg of praluzatamab ravtansine combined with CytomX’s pacmilimab anti-PD-L1 antibody.

“While we are encouraged by the emerging safety profile of 6 mg/kg, we do not plan to further advance this program alone given current financial market conditions and will be seeking a partnership,” CytomX CEO and Chairman Sean McCarthy, DPhil, said in a statement.

Veru (VERU)

Veru shares surged 20% this past week, jumping from $11.20 at the close July 1 to $13.46 yesterday. Most of that stock surge followed publication in The New England Journal of Medicine (NEJM) Evidence on Wednesday of results from a Phase III trial (NCT04842747) evaluating its sabizabulin in hospitalized moderate-severe COVID-19 patients at high risk for acute respiratory distress syndrome (ARDS) and death.

The trial evaluated oral, once-a-day dosing of sabizabulin 9 mg versus placebo in more than 200 hospitalized patients, with data available for 98 sabizabulin patients and 52 placebo patients. Sabizabulin, an oral, once-daily dual antiviral and anti-inflammatory agent, met the trial’s primary endpoint of death at or before day 60 by showing a “clinically and statistically meaningful” 55.2% relative reduction in deaths in the intent to treat population (ITT). At Day 60, the placebo group had a 45.1% mortality rate compared to the sabizabulin-treated group which had a 20.2% mortality rate.

In the overall study of 204 randomized patients, the reduction in the all-cause mortality following sabizabulin treatment (ITT population) was similar to the 51.6% reduction in deaths compared to placebo seem in an interim efficacy analysis.

“The overall conclusion of this Phase III study is that sabizabulin treatment has a clear mortality benefit compared to placebo in hospitalized COVID-19 patients at high risk for ARDS receiving standard of care treatment with no significant safety signals,” said Gary Barnette, PhD, Chief Scientific Officer of Veru and co-author of the NEJM Evidence publication.

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