Photo by Edward Jenner from Pexels

The U.S. Food and Drug Administration's approval machinery churned out a lot of disappointments in November. Most of the negative verdicts were tied to difficulties the agency had in inspecting facilities where investigational drugs are being manufactured, amid COVID-19-related restrictions.

Supernus Pharmaceuticals Inc. (SUPN), Alkermes Plc. (ALKS), Adamis Pharmaceuticals Corp. (ADMP), Bristol-Myers Squibb Co. (BMY), Liquidia Technologies Inc. (LQDA), and Revance Therapeutics Inc. (RVNC) were among the companies that either received complete response letters (which indicate that the application is not ready for approval) or saw the review periods extended.

Notable among the approvals issued during the month were Eiger Biopharmaceuticals Inc. (EIGR)'s progeria treatment Zokinvy and Sanofi SA (SNY)'s sutimlimab for treating hemolysis in adult patients with cold agglutinin disease. Alnylam Pharmaceuticals, Inc. (ALNY) was fortunate to get the FDA nod for its Oxlumo drug to treat primary hyperoxaluria type 1, ahead of the December 3 PDUFA date.

New molecular entity approvals totaled 44 thus far this year, compared to 41 approvals in the same period last year. Here are are the key PDUFA dates for December:

Vanda Seeks Twin Nods For Sleep Disorder Drug

• Company: Vanda Pharmaceuticals Inc. (VNDA).
• Type of Application: NDA & sNDA.
• Candidate: Hetlioz.
• Indication: Smith-Magenis Syndrome.
• Date: Dec. 1.

Hetlioz, a melatonin receptor agonist, was approved in Jan. 2014 to treat non—24-hour sleep-wake disorder in totally blind individuals. Vanda is now seeking an expansion to the label to include Hetlioz capsules. The company has also filed a new drug application for the liquid formulation of Hetlioz for the treatment of Smith-Magenis Syndrome.

Smith-Magenis Syndrome is a developmental disorder that is caused by a small deletion of human chromosome 17p, or in rare cases, due to a point mutation in the RAI1 gene which resides in the deleted region. This is estimated to affect one in about 15,200 to 25,000 people in the U.S. The most common symptom is a severe sleep disorder associated with significant disruption in the lives of patients and their families. Incidentally, Hetlioz faced a rejection as a treatment option for jet lag disorder in mid-2019.

BioCryst's Oral Hereditary Angioedema Drug Awaits Clearance

• Company: BioCryst Pharmaceuticals, Inc. (BCRX).
• Type of Application: NDA.
• Candidate: berotralstat, codenamed BCX7353.
• Indication: hereditary angioedema, or HAE, attacks.
• Date: Dec. 3.

Berotralstat, which would go by the brand name Orladeyo, is being evaluated as an oral, once-daily treatment for the prevention of HAE attacks. HAE is an inherited condition characterized by recurrent episodes of nonpruritic, nonpitting, subcutaneous, or submucosal swelling without the presence of urticarial lesions. It is caused by a low level or improper function of a protein called the C1 inhibitor and affects the blood vessels.

The company expects Orladeyo to fill an important unmet need for an oral HAE prophylactic and generate more than $500 million in global sales, Needham analyst Serge Belanger said in a recent note. "While we see no significant reason to doubt the FDA approval of Orladeyo by its PDUFA date, we remain skeptical of the product's overall potential given significantly lower efficacy levels (~44% attack rate reduction in ph 3 trials) vs. current injectable therapies with 80%-90% efficacy."

Will MacroGenics' Breast Cancer Drug Clear The FDA Hurdle?

• Company: MacroGenics Inc. (MGNX) & Zai Lab Ltd – ADR (ZLAB).
• Type of Application: BLA.
• Candidate: margetuximab.
• Indication: Breast cancer.
• Date: Dec. 18.

Margetuximab, a Fc-engineered, anti-HER2 mAb, is being evaluated in combination with chemotherapy for treating patients with with metastatic HER2-positive breast cancer. MacroGenics has partnered with Zai Lab in Greater China for the indication.

Amgen's Rituxan Biosimilar Faces FDA Decision

• Company: Amgen, Inc. (AMGN)/ AbbVie Inc. (ABBV).
• Type of Application: BLA.
• Candidate: ABP 798.
• Indication: Cancer.
• Date: Dec. 19.

ABP 798 is a biosimilar candidate to Roche Holdings AG's Basel ADR Common Stock (RHHBY) Rituxan.

Rituxan is an anti-CD20 monoclonal antibody, which has been approved for many indications, including non-Hodgkin's lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis, and microscopic polyangiitis with glucocorticoids. The active ingredient of ABP 798 is a monoclonal antibody with the same amino acid sequence as Rituxan.

Can Fibrogen/AstraZeneca's CKD-related Anemia Drug Win The Nod?

• Company: FibroGen Inc. (FGEN) & AstraZeneca plc. (AZN).
• Type of Application: NDA.
• Candidate: roxadustat.
• Indication: anemia of chronic kidney disease.
• Date: Dec. 20.

Roxadustat is an orally administered, small molecule HIF-PH inhibitor that promotes erythropoiesis, which is the process of producing red blood cells or erythrocytes. The NDA seeks approval of roxadustat for the treatment of anemia in chronic kidney disease, in both non-dialysis-dependent and dialysis-dependent patients.

Fibrogen is collaborating with AstraZeneca on the development and commercialization of roxadustat for the treatment of anemia in the U.S., China, and other markets in the Americas and in Australia, New Zealand, and Southeast Asia.

Myovant's Binary Event For Relugolix In Prostate Cancer In The Cards

• Company: Myovant Sciences Ltd. (MYOV).
• Type of Application: NDA.
• Candidate: relugolix.
• Indication: prostate cancer.
• Date: Dec. 20.

In late June, the FDA accepted for priority review the NDA for once-daily, oral relugolix, 120 mg, for the treatment of men with advanced prostate cancer. Relugolix is an oral gonadotropin-releasing hormone receptor antagonist that reduces production of testicular testosterone, a hormone known to stimulate the growth of prostate cancer, and ovarian estradiol, a hormone known to stimulate the growth of uterine fibroids and endometriosis.

Urovant Seeks Approval For Drug to Treat Overreactive Bladder

• Company: Urovant Sciences Ltd. (UROV).
• Type of Application: NDA.
• Candidate: vibegron.
• Indication: overactive bladder.
• Date: Dec. 26.

The FDA accepted the NDA for a review March 5, with the regulatory filing seeking approval for once-daily 75 mg vibegron for the treatment of patients with overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency.

‘Go or No-go' For Viatris' Copycat Version of Roche's Top-selling Cancer Drug

• Company: Viatris Inc. (VTRS).
• Type of Application: BLA.
• Candidate: MYL-1402O.
• Indication: Multiple cancer types.
• Date: Dec. 27.

Viatris, which formed following the merger of the erstwhile generic pharma company Mylan and Pfizer Inc. (PFE)'s generic unit Upjohn, has a tryst with the FDA in late December. The regulatory agency is scheduled to rule on the BLA for MYL-1402O, a proposed alternative to Roche's Avastin, for review under the 351(k) pathway. This is being developed in partnership with India's Biocon.

The BLA seeks approval of MYL-1402O for first-line and second-line treatment of patients with metastatic colorectal cancer in combination with fluorouracil-based chemotherapy; first-line use for patients with non-squamous non-small cell lung cancer; recurrent glioblastoma; metastatic renal cell carcinoma in combination with interferon alfa; and persistent, recurrent, or metastatic cervical cancer.

Can Second Time Be The Charm For Osmotica

• Company: Osmotica Pharmaceuticals PLC. (OSMT).
• Type of Application: NDA.
• Candidate: Ontinua (arbaclofen) ER.
• Indication: spasticity in patients with MS.
• Date: Dec. 29.

Osmotica originally submitted the NDA for arbaclofen ER in 2015, with the FDA issuing a complete response in June 2016, citing irregularities and deviations from good clinical practices at study sites of the initial Phase 3 trial. The company submitted in late June an amended NDA, and in late July, it said the regulatory agency had deemed its submission as a complete, class 2 response.

"Management noted that the questions received from FDA so far have been reasonable and confirmatory in nature, and that it feels very good about its answers to the agency's information requests," SVB Leerink analyst Ami Fadia said in a recent note. "All in all, it clearly sees great potential in arbaclofen, but is cautiously optimistic on the approval given the history of the product."

Scpharma Hopes For No Heartache In Second Try For Heart Failure Drug

• Company: Scpharmaceuticals Inc. (SCPH).
• Type of Application: NDA.
• Candidate: Furoscix.
• Indication: worsening heart failure due to congestion.
• Date: Dec. 30.

Furoscix is a proprietary, subcutaneously-delivered furosemide solution, as an outpatient alternative for the treatment of worsening congestive heart failure. This is scPharma's second try for Furoscix following a CRL issued in 2018, wherein the agency sought additional human factor studies, device modifications, and potentially a clinical validation study.

The PDUFA event is a significant catalyst for the stock, SVB Leerink analyst Fadia said. The analyst stated she is cautiously optimistic on the approval, given the regulatory history, and put an 80% probability of success on approval. If approved, the analyst models a price target for $20 for the shares.

Athenex Gears to Face Verdict On Drug to Treat Precancerous Skin Condition

• Company: Athenex Inc. (ATNX).
• Type of Application: NDA.
• Candidate: tirbanibulin ointment.
• Indication: actinic keratosis.
• Date: Dec. 30.

The NDA for tirbanibulin ointment was accepted for review on March 9. Athenex has granted Almirall, S.A., an exclusive license for R&D and commercializing tirbanibulin ointment in the U.S. and European countries, including Russia. Actinic Keratosis is the most common pre-cancerous condition in dermatology and affects more than 55 million Americans, and accounts for between 14-29% of dermatologist visits in the U.S., Athenex said.

Vertex Seeks Label Expansions For Cystic Fibrosis Medications

• Company: Vertex Pharmaceuticals Incorporated (VRTX).
• Type of Application: sNDAs.
• Candidate: Trikafta (elexacaftor, tezacaftor and ivacaftor), Symdeko (tezacaftor and ivacaftor) and Kalydeco (ivacaftor).
• Indication: cystic fibrosis.
• Date: Dec. 30.

The sNDAs were accepted by the FDA for review September 1. These regulatory submissions are intended to expand the labels for Trikafta, Symdeko, and Kalydeco to include additional rare CFTR mutations, Vertex said. Potential approvals will also allow certain people with cystic fibrosis, who are currently eligible for Kalydeco to become eligible for Symdeko or Trikafta, and certain people currently eligible for Symdeko to become eligible for Trikafta.

Adcom Calendar

The Center for Biologics Evaluation and Research's Vaccines and Related Biological Products Advisory Committee, or VRBPAC, will meet December 10, in an open session to discuss emergency use authorization of the vaccine candidate developed by Pfizer-BioNTech SE – ADR (BNTX) for the prevention of COVID-19 in individuals 16 years of age and older.

The companies filed with the FDA an application for EUA November 20. Moderna (MRNA) is also likely to meet with VRBPAC once its mandated safety data is accrued and it files for EUA.