In a seeming role-reversal, FDA steps up action over Thanksgiving week while EMA goes on holiday.

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Although usually thought of as a well-deserved respite from governmental rulings, the US Food and Drug Administration seized on Thanksgiving week as a demonstration of its zeal to pump out rulings, while the European Medicines Agency apparently took the week off.

Let’s look at the recent American regulatory scene, zeroing in first with the struggles of a New Jersey company to get their first approval, and then switch to another key victory for Keytruda, this time in China.

1) Almost a year after the FDA first snubbed Immunomedics Inc.’s (Morris Plains NJ) lead drug, the ADC biotech is returning to plead their case again. (Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs.)

The company has resubmitted their BLA, seeking accelerated approval for sacituzumab govitecan for triple-negative metastatic breast cancer, Endpoints reports. (BLA stands for “biologics license application” and is defined as “a request for permission to introduce, or deliver for introduction, a biologic product into interstate commerce.”)

Immunomedics said the FDA noted manufacturing issues in their rebuff. Soon afterwards, it emerged that the agency had previously cited the company for a breach of data veracity in the months leading up to their PDUFA, although the publicly distributed report is heavily redacted, and it remains unclear if the data breach was directly connected to the FDA rejection. (PDUFA stands for the the Prescription Drug User Fee Act, a law passed by the US Congress in 1992 which allowed the FDA to collect fees from drug manufacturers to fund the new drug approval process.)

Endpoints reports that Immunomedics told it that they met with the FDA in May and “validated” a CRL (complete response letter) plan and gave a “successful update” in September. “The FDA was very favorable towards our plan,” they said.

Unlike the EMA, the FDA does not reveal the reasons for rejections. But the data breach report, written after an August inspection, was harsh.

“There is no assurance that samples and batch records form the [redacted] process validation and commercial batches manufactured prior to February 2018 were not impacted by the data integrity breach,” agency inspectors wrote.

In a 13-point document, they listed poor retesting procedures, backdating documents, manipulation of bioburden samples, and facility design flaws, among other issues.

Immunomedics’ acituzumab govitecan, or IMMU-132, is an antibody drug conjugate that is intended to deliver a specific payload straight to the tumor. In a Phase 2 clinical trial published in the New Engalnd Journal of Medicine, the drug had a 33.3% response rate and exhibited a median progression-free survival of 5.5 months.


Now let’s take a look at the “holiday” week’s FDA action, ICER advisories and China’s approval of Keytruda:

2) The FDA approved Aquestive Therapeutics Inc.’s (Warren NJ) application to market Exservan, its oral film formulation of a decades-old treatment for amyotrophic lateral sclerosis. In 1995 riluzole became the first FDA-approved therapy for ALS, which remains incurable. Its exact mechanism of action is unknown but it’s been proposed that the drug blocks the release of glutamate from nerve cells, thereby alleviating glutamate-induced deterioration. As a result, the original drug was shown to delay symptoms and even death. While the branded version, Rilutek, is still on the market (Covis Pharma bought the US rights a few years ago, and Sanofi retains worldwide control), Aquestive’s bigger challenge will be competing against generics, which can cost as little as $74.06 for 60 tablets on GoodRx.

3) Elsewhere, Global Blood Therapeutics Inc. (South San Francisco) announced it received FDA approval for its drug Oxbryta (voxelotor) in treating adults and children ages 12 years and older with sickle cell disease (SCD). The FDA approval of Oxbryta was made possible thanks to a highly positive Phase 3 study known as HOPE. This late-stage study recruited about 274 SCD patients who were ages 12 years and older. The global SCD market is expected to reach $5.5 billion by 2023. These patients have a major issue with hemoglobin.

4) The FDA approved a new system for placement of tympanostomy tubes in children with otitis media that does not require general anesthesia. The Tubes Under Local Anesthesia (Tula) system, from Tusker Medical Inc. (Menlo Park CA), is the first tympanostomy tube delivery system that can be performed in young children under local anesthesia in a physician’s office. The system uses a small electrical current to deliver a local anesthetic into the ear drum prior to tube insertion. It is approved for use in adults and children as young as 6 months of age. In young children, the tympanostomy tube placement has traditionally been performed in a hospital setting or surgery center udder general anesthesia.

5) The FDA has declined approval of Zimhi, a high-dose naloxone injection product for the treatment of opioid overdose, according to a statement from the manufacturer, Adamis Pharmaceuticals Corp. (San Diego). In a complete response letter (CRL), the FDA said it cannot approve the new drug application for Zimhi in its present form and provided recommendations needed for resubmission, the company said. The CRL did not raise any clinical safety or efficacy issues. The questions raised by the FDA relate generally to chemistry, manufacturing, and controls (CMC), Adamis said. The company plans to expand on the CMC testing that it has already provided to the FDA to satisfy the concerns outlined in the CRL.

6) A major competitor to Biogen Inc.’s Spinraza franchise could arrive as early as this coming May, as Roche Holding AG (Basel CHE) and its biotech partner obtained a priority review for risdiplam. FDA regulators will make a decision on the spinal muscular atrophy drug by May 24, 2020, according to PTC Therapeutics Inc. (South Plainfield NJ), who is garnering $15 million in a milestone payment for the NDA filing acceptance. The move closely follows topline data from the Phase 3 SUNFISH trial, in which risdiplam met the primary endpoint on change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment, compared to placebo. The results confirmed earlier findings from part one of the study.

7) British drugmaker AstraZeneca PLC (London) said on Friday its immunotherapy cancer treatment Imfinzi has been granted a speedy review by the FDA for the treatment of a particularly aggressive type of lung cancer. The company said the FDA accepted its supplemental application and granted priority review to Imfinzi for the treatment of previously untreated late-stage small cell lung cancer (SCLC). The FDA decision is a boost for the treatment as it competes against similar medicines from rivals Merck and Roche, and follows data in September which showed Imfinzi prolonged survival in SCLC patients when used with chemotherapy.

8) The FDA has granted the Usona Institute (Madison WI) breakthrough therapy designation for psilocybin for the treatment of major depressive disorder (MDD). This marks the second time the FDA has granted breakthrough designation for psilocybin, the psychoactive ingredient in “magic mushrooms.” In October 2018, Compass Pathways received the designation to test the safety and efficacy of psilocybin-assisted therapy for treatment-resistant depression, as reported by Medscape. The Usona Institute is a nonprofit medical research organization that conducts and supports preclinical and clinical research to further the understanding of the therapeutic effects of psilocybin and other consciousness-expanding medicines.

9) In an evidence report released last week looking at the cost-effectiveness of Janus kinase (JAK) inhibitors to treat rheumatoid arthritis (RA) over a one-year time horizon, the US-based Institute for Clinical and Economic Review (ICER) said that AbbVie Inc.’s (North Chicago) new RA drug Rinvoq (upadacitinib) provides “marginal clinical benefit” versus its tumor necrosis factor (TNF) blocker Humira (adalimumab), but at a higher cost. The group found that compared with Humira, Rinvoq’s value-based price benchmark is between $44,000 to $45,000 per year, representing a discount of 25% to 26% off of its annual list price of $59,860, which ICER said “is consistent with the rebates we assume the manufacturer is currently offering.”

10) Aside from Rinvoq, ICER also set out to assess Pfizer Inc.’s (NYC) and Eli Lilly & Co.’s (Indianapolis) respective JAK inhibitors Xeljanz (tofacitinib) and Olumiant (baricitinib) versus Humira, but “gaps in the literature” limited the analysis to only Rinvoq versus Humira in targeted immune modulator-naïve patients with prior failure by conventional disease-modifying antirheumatic drugs (DMARDs).

11) And elsewhere in the world, Merck & Co.’s (Kenilworth NJ) anti-PD-1 blockbuster, Keytruda, grabbed another win. The newest jewel onto the crown for the company is the Chinese approval of the therapy in combination with carboplatin and paclitaxel for the first-line cases of metastatic squamous non-small cell lung cancer (NSCLC). With this new indication, Keytruda is now approved to treat both squamous and non-squamous NSCLC in conjunction with chemotherapy, as well as a subgroup of NSCLC patients as a monotherapy.

Have a great week.

Steve Walker

Founder & Editor

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