==BridgeBio Pharma (BBIO) : Breakthrough Therapy Designation to oral infigratinib

 

BridgeBio Pharma announces that the FDA has granted Breakthrough Therapy Designation to oral infigratinib under development for children with achondroplasia

• Breakthrough Therapy Designation was granted based on preliminary clinical evidence from the PROPEL 2 clinical trial, meeting the FDA's requirement of potentially demonstrating substantial improvement in efficacy over available therapies on clinically significant endpoint(s).
• BridgeBio will leverage the benefits of Breakthrough Therapy Designation to expedite the development and regulatory review of infigratinib in the United States and if approved, infigratinib could be the first-in-class oral therapeutic option for children living with achondroplasia.
• In Cohort 5 of PROPEL 2 (0.25 mg/kg/day), oral treatment with infigratinib resulted in a statistically significant and sustained increase in annualized height velocity (AHV), with a mean change from baseline of +2.51cm/yr at Month 12, and +2.50 cm/yr at Month 18 (p=0.0015) and statistically significant improvement in body proportionality at Month 18.

==ARS Pharmaceuticals (SPRY) : FDA Declines to Approve No-Shot Alternative to EpiPen, Asks for Additional Data

 

ARS Pharmaceuticals receives Complete Response Letter from FDA for neffy NDA

• Co announced that the FDA issued a Complete Response Letter (CRL) regarding its New Drug Application (NDA) for neffy (epinephrine nasal spray) in the treatment of Allergic Reactions (Type I), including anaphylaxis for adults and children =30 kg. ARS Pharma plans to submit a Formal Dispute Resolution Request (FDRR) to appeal the issuance of this CRL.
• In the letter, the FDA requested completion of a pharmacokinetic/pharmacodynamic study assessing repeat doses of neffy compared to repeat doses of an epinephrine injection product under allergen-induced allergic rhinitis conditions to support approval. This request comes after the recommendation of the FDA Advisory Committee (PADAC) in May 2023 to approve neffy without the need for additional studies to demonstrate its efficacy or safety. Further, FDA and ARS Pharma previously aligned in August 2023 on final physician's labeling and a post-marketing requirement to conduct this study as informative for labeling.
  • The PADAC meeting was held on May 11, 2023, and concluded a favorable benefit-risk profile of neffy, with a 16:6 vote in favor for adults and 17:5 vote in favor for children (=30 kg) for the treatment of patients with allergic reactions (Type I), including anaphylaxis. In that session, no member of the Committee raised specific concerns about the result of the completed study in people with allergen-induced acute rhinitis with single-dose neffy, which showed enhanced absorption during the time period when a clinical response would be expected.
• As ARS Pharma previously agreed with FDA to conduct a repeat-dose study under allergen-induced allergic rhinitis conditions as a post-marketing commitment, ARS Pharma anticipates a resubmission to the FDA in the first half of 2024, positioning ARS Pharma for an anticipated FDA action date in the second half of 2024.
• ARS Pharma expects to have anticipated cash, cash equivalents and short-term investments on hand of approximately $195 million at the time of the anticipated launch of neffy, if approved in the second half of 2024.
• The CRL requested additional information on nitrosamine impurities to be tested for based on new draft guidance issued after the neffy NDA submission. ARS Pharma does not believe the additional testing would be a rate-limiting step for its resubmission to the FDA.

===Verve Therapeutics (VERV) reported earnings on Mon 7 Nov 22 (b/o)

• reports VERVE-101 Investigational New Drug Application placed on hold by FDA 

Verve Therapeutics reports VERVE-101 Investigational New Drug Application placed on hold by U.S. Food and Drug Administration 

• Verve announced today that the U.S. Food and Drug Administration (FDA) has placed a hold on its IND application to conduct a clinical trial evaluating VERVE-101 in patients with heterozygous familial hypercholesterolemia (HeFH), a prevalent and potentially life-threatening subtype of atherosclerotic cardiovascular disease (ASCVD), in the United States. VERVE-101 is a novel, investigational gene editing medicine designed to be a single-course treatment to permanently turn off the PCSK9 gene in the liver to reduce disease-driving low-density lipoprotein cholesterol (LDL-C). VERVE-101 is currently being evaluated in the heart-1 Phase 1 clinical trial in New Zealand and the United Kingdom (U.K.). Verve submitted its IND application for VERVE-101 to the FDA in October and received notification of a hold from the FDA on Friday, November 4, 2022. The company expects to receive an official letter with the FDA's questions within 30 days. Verve plans to provide updates pending engagement with the FDA and intends to work closely with the FDA to resolve the hold as promptly as possible in order to initiate dosing in the U.S.
• heart-1 Trial Update: Clinical data from the ongoing heart-1 study in New Zealand and the U.K. were not included in the IND package submitted to the FDA. Verve has completed dosing of VERVE-101 in the first dose cohort of the dose-escalation portion of the heart-1 trial, which was well tolerated in all three patients. There have been no treatment-related adverse events reported to date, and all adverse events observed have been Grade 1 in nature. The independent Data Safety Monitoring Board (DSMB) has reviewed safety data from the first cohort and recommended dose escalation to the planned second dose level, which is expected to begin soon. Enrollment efforts are ongoing in New Zealand and the U.K. The company plans to report initial safety and pharmacodynamic data for all dose cohorts of the dose-escalation portion of the heart-1 study at a medical meeting in the second half of 2023.

===Amylyx Pharmaceuticals (AMLX) announces FDA Advisory Committee supports approval of AMX0035 for the treatment of ALS

 

Amylyx Pharmaceuticals announces FDA Advisory Committee supports approval of AMX0035 for the treatment of ALS 

• Co announced the FDA Peripheral and Central Nervous System Drugs Advisory Committee (PCNSDAC) voted (7 yes votes and 2 no votes) that the available evidence of effectiveness is sufficient to support approval of AMX0035 (sodium phenylbutyrate and taurursodiol [also known as ursodoxicoltaurine]) for the treatment of amyotrophic lateral sclerosis (ALS).
• The PCNSDAC's decision was based on a review of all available evidence, including new analyses submitted for discussion at the September 7 meeting and the information presented at the March 30, 2022, PCNS meeting.
• The PCNSDAC recommendations, while not binding, will be considered by the FDA in its review of the pending New Drug Application (NDA) for AMX0035. As previously reported, the Prescription Drug User Fee Act target action date for the NDA is September 29, 2022, which was extended by the FDA to allow more time to review additional analyses of data from the Company's clinical studies.

-=Clovis Oncology (CLVS) to seek FDA approval for ovarian cancer drug as a maintenance therapy

 

Clovis Oncology Rubraca significantly improves progression-free survival in first-line maintenance treatment in women with ovarian cancer regardless of their biomarker status in phase 3 athena-mono trial

• ATHENA study evaluating Rubraca monotherapy versus placebo (ATHENA-MONO) successfully achieved the primary endpoint of improved PFS in both populations in the primary efficacy analyses: HRD-positive and all patients randomized.
• Median PFS of 20.2 months for Rubraca vs 9.2 months for placebo in the ITT population.
• The exploratory PFS endpoints were also achieved in both HRD-negative and BRCA mutant subgroups of patients.
• Safety of Rubraca observed in ATHENA-MONO was consistent with both the current US and European labels.
• ATHENA-MONO results will serve as the basis of a supplemental NDA for US label expansion to be submitted during Q2 2022; European submission to follow during Q3 2022.
• These data, including additional analyses, have been submitted for presentation at the American Society of Clinical Oncology Annual Meeting in June 2022.

AbbVie (ABBV) : FDA warning on the company's arthritis drug Rinvoq

• FDA said makers of janus kinase inhibitors, or JAK inhibitors, would have to warn users against a myriad of conditions. The requirement impacts AbbVie's Rinvoq, Pfizer's Xeljanz and Lilly's Olumiant. All three are JAK inhibitors for arthritis and other inflammatory conditions.

The order also impacts drugs from Pfizer (PFE) and Eli Lilly (LLY). A recent test of Pfizer's Xeljanz indicated the drug increases the risk of heart issues, blood clots, cancer and death in patients treated for arthritis and other inflammatory conditions. AbbVie's (ABBV) Rinvoq and Lilly's Olumiant belong to the same drug class.

Recently, AbbVie said it plans to test a next-generation version of Alzheimer's drug Aduhelm beginning late this year or early next. Aduhelm, a Biogen (BIIB) drug, gained approval in June and helped shift researchers' focus to the beta amyloid theory of treatment.

Beta amyloid is a type of plaque that builds up in the brains of Alzheimer's patients. Some believe removing it will help improve patients' cognition. The theory doesn't have full support from the scientific community, however. On the company's second-quarter earnings call, AbbVie President Michael Severino said the company had monitored this area for several years.

Seeking Diversity From Humira

A number of companies have launched Humira biosimilars in Europe and plan to launch those same copycats in the U.S. in 2023. That's problematic for AbbVie stock. Humira accounted for more than 43% of adjusted sales in 2020.

In the U.S., Humira grew 19.2%. But biosimilars chipped away at international sales, which fell 7.9% on a strict as-reported basis. Overall, first-quarter Humira sales rose 3.5%.

Total sales surged 37.6% in 2020, hitting $45.78 billion. But that includes the takeover of Botox-maker Allergan. On a comparable operational basis, sales inched up 3.3%.

On May 18, CEO Gonzalez faced questions from the Oversight and Reform Committee regarding the company's pricing and patent practices for Humira. Gonzalez acknowledged Humira costs more in the U.S. than it does in socialized health care systems abroad.

Rinvoq: The Next Humira?

AbbVie stock is susceptible to swings in opinion on Rinvoq. The company's bread-and-butter drug is TNF blocker Humira. Humira treats a number of inflammatory issues, including types of arthritis. But it's set to face biosimilar rivals in the U.S. in 2023. Rinvoq won't see copycat rivals for some time.

The FDA also noted the warning label requirement doesn't apply to JAK inhibitors from Bristol Myers Squibb (BMY) and Incyte (INCY) known as Inrebic and Jakafi, respectively. These drugs treat blood disorders and aren't being used in arthritis or for other inflammatory conditions.

-=Ardelyx (ARDX) : FDA questions its kidney disorder treatment drug

•  Company receives letter from the FDA identifying deficiencies in the NDA for tenapanor

Ardelyx receives letter from the FDA identifying deficiencies in the NDA for tenapanor that preclude discussions of labeling and post-marketing requirements/commitments at this time  

• Ardelyx received a letter from the FDA on July 13 stating that, as part of its ongoing review of the company's New Drug Application (NDA) for the control of serum phosphorus in adult patients with chronic kidney disease (CKD) on dialysis, the FDA has identified deficiencies that preclude discussion of labeling and post-marketing requirements/commitments at this time. The letter stated that the notification does not reflect a final decision on the information under review.
  • Ardelyx is advancing tenapanor, a novel product candidate to control serum phosphorus in adult patients with CKD on dialysis, for which the company submitted an NDA to the FDA in June 2020. In April 2021, the FDA extended the PDUFA date to July 29, 2021, following the submission of additional analyses determined to be a major amendment.
• The company immediately requested a meeting to discuss the deficiencies and was notified by the FDA today that the request for a meeting was denied.
  • While the FDA has not provided specific details regarding the deficiencies, the FDA noted that a key issue is the size of the treatment effect and its clinical relevance.
  • The company plans to work with the FDA to learn more about the identified deficiencies and will seek to resolve them as quickly as possible.

Protalix BioTherapeutics (PLX) receives Complete Response Letter for Pegunigalsidase Alfa from FDA

  

 

 

 

Protalix BioTherapeutics provides update on FDA Complete Response Letter for pegunigalsidase alfa (PRX-102) for the proposed treatment of adult patients with Fabry disease 

The CRL did not report any concerns relating to the potential safety or efficacy of PRX--102 in the submitted data package.

In the CRL, the FDA noted that an inspection of Protalix's manufacturing facility in Carmiel, Israel, including the FDA's subsequent assessment of any related findings, is required before the FDA can approve the BLA. Due to travel restrictions, the FDA was unable to conduct the required inspection during the review cycle. The FDA explained that it will continue to monitor the public health situation as well as travel restrictions, and is actively working to define an approach for scheduling outstanding inspections. With respect to the third-party facility in Europe at which fill and finish processes are performed for PRX-102, due to COVID--19, the FDA reviewed records in lieu of a pre-licensing inspection. In the CRL, the FDA stated that it will communicate remaining issues to the facility in order to seek prompt resolution of any pending items.

In addition to the foregoing, the FDA noted that Sanofi's (SNY) Fabrazyme was recently converted to full approval which must be addressed in the context of any potential resubmission seeking accelerated approval of PRX-102. Protalix intends to work collaboratively with the agency to identify the most expeditious pathway to approval, including accelerated approval. Protalix remains confident that it will be able to work with the FDA to resolve these issues and provide a new, alternative drug to Fabry patients. Protalix intends to request a Type-A meeting with the FDA, and will provide further updates on next steps after the meeting.

-=Adamis Pharma (ADMP) submits a Covid drug to FDA

• Adamis is requesting the FDA's permission for investigational use of its Covid treatment drug Tempol. 

Tempol has demonstrated both potent anti-inflammatory, anticoagulant, and antioxidant activity. Both inflammatory cytokines and reactive oxygen species (ROS) from cells of the immune system called macrophages and neutrophils damage the lung in Acute Respiratory Distress Syndrome (ARDS). In animal models, Tempol has been shown to decrease proinflammatory cytokines (cytokine storm), and through its potent antioxidant activity has been shown to decrease the harmful effects of ROS. In addition, Tempol has been shown to decrease platelet aggregation, a problem observed in many COVID-19 patients. Numerous published articles describing animal models of ARDS show Tempol to cause a decrease in lung inflammation and preserve lung pathology associated with acute and chronic lung injury. To this end, Tempol has been shown to decrease the genes (HIF-la and HIF-2a) associated with hypoxia. Hypoxia is a key indicator often associated with severe disease and a poor outcome. Controlling hypoxia and the cytokine storm can be considered essential to the successful treatment of COVID-19.

Dr. Dennis J. Carlo, President and CEO of Adamis commented: “With over 23 million COVID-19 infections in the US and over 394,000 deaths in the US (according to the CDC), additional treatments are urgently warranted. We believe that Tempol could play a pivotal role not only in the treatment of COVID-19, but actually in preventing hospitalization. With new mutations occurring in the virus, it is apparent there is an ongoing need for new therapies. 

=Immunomedics (IMMU) : cancer treatment fails to win accelerated approval from the FDA

Immunomedics receives complete response letter from the FDA for Sacituzumab Govitecan BLA 

(Reuters) - Immunomedics Inc said on Thursday the U.S. Food and Drug Administration declined to grant accelerated approval for its breast cancer treatment, sacituzumab.

The company said it will request a meeting with the agency and work closely with the health regulator in its effort to launch the treatment as soon as possible.

"The issues related to approvability in the CRL (complete response letter) were exclusively focused on Chemistry, Manufacturing and Control matters and no new clinical or preclinical data need to be generated," Immunomedics Chief Executive Officer Michael Pehl said.

-=Epizyme (EPZM) : FDA lifts hold on trial enrollments

Shares of Epizyme Inc. (EPZM) shot up 5% Monday after the company said the Food and Drug Administration lifted its hold on the enrolling of new patients in trials of its treatment for non-Hodgkin lymphoma. The FDA's hold had followed a report of a case of T-cell lymphoblastic lymphoma (T-LBL) in its tazemetostat pediatric study. Epizyme said its response to the FDA included a comprehensive assessment of the risk of secondary malignancies. "The Epizyme team has worked diligently to provide a comprehensive response back to the FDA, and through constructive dialogue, we successfully resolved the partial clinical hold," said Chief Executive Robert Bazemore. "This allows us to turn our full attention to our key priorities: preparing for our first NDA submission for tazemetostat in epithelioid sarcoma and defining our registration path in FL." The stock had tumbled 31% over the past three months through Friday.

-=Acadia Pharmaceuticals (ACAD): FDA finds drug has no additional safety problems

Acadia Pharmaceuticals (ACAD) stock spiked 19.3% in extremely heavy Thursday afternoon trade after the U.S. Food and Drug Administration found that its drug, Nuplazid, continued to have more benefits than risks for patients. Nuplazid is an antipsychotic medication used for the hallucinations and delusions connected to Parkinson's disease psychosis, but concerns had been raised by caregivers, health care providers and health watchdogs that the drug wasn't helping and might even be hurting patients, according to a CNN report. The FDA based its determination on postmarketing reports -- the drug was first launched in the U.S. in May 2016 -- as well as other data, and said it did not find "any new or unexpected safety findings." More than 8,000 cases of side effects have been reported by individuals taking Nuplazid to the FDA's Adverse Events Reporting System (FAERS), which was one of the sources reviewed by the regulator, including around 2,700 serious cases and nearly 1,150 death cases. But the FDA said that Nuplazid and others of its kind already have warnings on their boxes indicating a higher risk of death in elderly patients, and the agency considered that individuals with Parkinson's disease psychosis are more at risk of death due to their age, disease and other medical conditions. Nuplazid brought in net sales of around $125 million last year, according to Acadia's financial filings. Company shares have surged nearly 6% over the last three months, compared with a 6% rise in the S&P 500 SPX, +0.75% and a 8.2% rise in the Dow Jones Industrial Average DJIA, +0.91%

=Acorda (ACOR) : FDA delays review of Parkinson's treatment

Shares of Acorda Therapeutics(ACOR) slid 19% Thursday, after the company said the U.S. Food and Drugs Administration has extended the review period for a treatment for symptoms of Parkinson Disease. The extension comes after Acorda submitted additional information on its Inbrija, an inhaled levodopa therapy that aims to reduce off times, or the periods when standard levodopa treatment stops working. The FDA determined that the additional information constituted a major amendment that would take longer to review. The regulator moved the review date back to Jan. 5, 2019 from Oct. 5, 2018. Parkinson's is a progressive neurodegenerative disorder that affects about 1 million people in the U.S. and 1.2 million people in Europe. Acorda shares have fallen 13.8% in 2018, while the S&P 500 SPX, +0.04% has gained 8.1%.

=Calithera Biosciences (CALA) : Fast Track designation for CB-839 in combination with cabozantinib

Calithera Biosciences announces that the FDA has granted Fast Track designation to CB-839 in combination with cabozantinib for the treatment of patients with metastatic renal cell carcinoma

=Alkermes (ALKS) : FDA has accepted for review the NDA for ALKS 5461

Alkermes announces that the FDA has accepted for review the NDA for ALKS 5461 for the adjunctive treatment of major depressive disorder in patients with an inadequate response to standard antidepressant therapies 

• FDA's acceptance of the ALKS 5461 NDA and rescission of the Refusal to File letter issued March 30, 2018 follows productive interactions with the Agency in which Alkermes clarified certain aspects of the NDA submission. No additional data or analyses were submitted by Alkermes to FDA.
• FDA's target action date for the ALKS 5461 NDA is Jan. 31, 2019.

=Bellicum Pharma (BLCM) : FDA lifts the clinical hold on studies of BPX-501

• The University of Texas MD Anderson Cancer Center acquired Bellicum Pharmaceuticals in February 2024. The acquisition included Bellicum's cell therapy technologies, intellectual property, and clinical-grade stocks. MD Anderson also acquired Bellicum's Houston facility in 2020.

Bellicum Pharma: FDA has lifted the clinical hold on studies of BPX-501 in the U.S. 
The decision follows consultation with the FDA and agreement on amendments to the study protocols including guidance on monitoring and management of neurologic adverse events. Bellicum will be working with U.S. clinical sites to resume patient recruitment based on the amended protocols.

Progenics Pharma (PGNX) : FDA extends review of the New Drug Application for AZEDRA

Progenics Pharma announces that they have received notification from the FDA that the Agency will extend its review of the New Drug Application for AZEDRA (iobenguane I 131) by three months to July 30, 2018

** charts before announcement **

  

** charts after announcement **

  

-=Bellicum Pharma (BLCM) : U.S. studies of BPX-501 have been placed on clinical hold

Bellicum Pharma received FDA notice that U.S. studies of BPX-501 have been placed on clinical hold after three cases of encephalopathy deemed as possibly related 

Bellicum is awaiting formal communications from the FDA to determine the requirements for resuming studies, and will be working closely with the FDA to address their questions.

• The FDA clinical hold does not affect the ongoing BP-004 registration trial in Europe. Encephalopathy has been reported in the allogeneic stem cell transplant literature. Risk factors for encephalitis/encephalopathy after allogeneic stem cell transplants include prolonged immunodeficiency, selected medications, infections, and inflammatory processes such as graft versus host disease. Bellicum has treated more than 240 patients with BPX-501 cells on three allogeneic haploidentical stem cell transplantation protocols.These three cases are complex, with a number of potential confounding factors-including, in certain of the cases, prior failed transplants, prior history of immunodeficiency, concurrent infection, and administration of rimiducid in combination with other medications. Bellicum is working with FDA to evaluate the risk of encephalopathy in patients receiving BPX-501.

Antares Pharma (ATRS) : FDA found deficiencies in the drug Xyosted

Antares Pharma (ATRS) announced Thursday that the U.S. Food and Drug Administration had found deficiencies in the drug Xyosted (testosterone enanthate) during its review process, the company said in a statement. Antares submitted the Xyosted application in December 2016. Antares stock was up 60% this year,

 

Antares Pharma received FDA letter - identified deficiencies as part of their ongoing review of the New Drug Application for XYOSTED

• Co announced that, on October 11, 2017, the Company received a letter from the FDA stating that, as part of their ongoing review of the New Drug Application (NDA) for XYOSTED (testosterone enanthate) injection, they have identified deficiencies that preclude the continuation of the discussion of labeling and postmarketing requirements/commitments at this time. The letter does not specify the deficiencies identified by the FDA and there has been no further clarification of the deficiencies by the FDA at this time.
• Anticipates receiving further clarification from the FDA on or before the Prescription Drug User Fee Act (PDUFA) date of October 20, 2017.

Aerie Pharmaceuticals (AERI) : glaucoma drug effectively lowers eye pressure

  

Oct 11 (Reuters) - Aerie Pharmaceuticals Inc's experimental glaucoma treatment Rhopressa is effective in lowering eye pressure, a preliminary review by the U.S. Food and Drug Administration concluded.

The review, posted on Wednesday on the FDA's website, comes two days ahead of a meeting of outside experts who will advise the agency on whether the treatment should be approved.

Glaucoma, a condition caused by damage to the optic nerve, is the second-leading cause of blindness in the world. It is expected to affect more than 4 million Americans by 2030, up from 2.7 million today.

*****

Description

Aerie Pharmaceuticals, Inc. is a clinical-stage pharmaceutical company. The Company is engaged in the discovery, development and commercialization of therapies for the treatment of patients with glaucoma and other diseases of the eye. The Company's product candidates include Rhopressa (netarsudil ophthalmic solution) 0.02% (Rhopressa), and Roclatan (netarsudil/latanoprost ophthalmic solution) 0.02%/0.005% (Roclatan). The Company's product candidates are designed to lower intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. Its Rhopressa is a once-daily eye drop. Rhopressa inhibits Rho kinase (ROCK), and the norepinephrine transporter (NET), which are both biochemical targets for lowering IOP. Its Roclatan is a once-daily, fixed-dose combination of Rhopressa and latanoprost, which is a prescribed drug for the treatment of patients with open-angle glaucoma. The Company is engaged in conducting Phase III clinical trial for Roclatan.

Key stats and ratios

	Q2 (Jun '17)	2016
Net profit margin	-	-
Operating margin	-	-
EBITD margin	-	-
Return on average assets	-41.29%	-48.63%
Return on average equity	-84.74%	-159.62%
Employees	95