Dec 23, 2019: Eisai Co. announced that the U.S. Food and Drug Administration (FDA) approved the New Drug Application for its in-house discovered and developed orexin receptor antagonist DAYVIGOTM (lemborexant) for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults.
It will commercially available in 5 mg and 10 mg tablets following scheduling by the U.S. Drug Enforcement Administration (DEA).
Lemborexant is characterized by difficulties with sleep onset and/or sleep maintenance is supposed to be through antagonism of orexin receptors.
The orexin neuropeptide signaling system plays an important role in wakefulness.Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to orexin receptors OX1R and OX2R is reflection to restrain wake drive.
This approval was based on the results of a clinical development program that incorporated two pivotal Phase III studies (SUNRISE 2 and SUNRISE 1), which evaluated DAYVIGO versus comparators for up to one month and DAYVIGO versus placebo for six-months, respectively, in a totality of about 2,000 adult patients with insomnia. https://www.eisai.com/news/2019/news201993.html
Dec 23, 2019: Roche and Sarepta Therapeutics announced the signing of a licensing agreement providing Roche exclusive commercial rights to SRP-9001 (AAVrh74.MHCK7.micro-dystrophin), Sarepta’s investigational gene therapy for the Duchenne muscular dystrophy (DMD), outside the United States.
Under the conditions of the agreement, Sarepta will receive a direct payment of $750million in cash and $400million in equity. Sarepta is eligible to obtain regulatory and sales milestones and royalties on net sales.
Roche and Sarepta will even contribute to global development expenses. It combines Roche’s global reach, commercial presence and regulatory expertise with Sarepta’s gene therapy candidate for DMD to accelerate access to SRP-9001 for the patients outside the United States.
DMD is an X-linked rare degenerative neuromuscular disorder causing severe progressive muscle loss and premature death, it affects approximately one in every 3,500 – 5,000 male births worldwide.
SRP-9001, currently in clinical development for the DMD, is designed in order to deliver the microdystrophin-encoding gene directly to the muscle tissue for the targeted production of the microdystrophin protein. https://www.roche.com/media/releases/med-cor-2019-12-23.htm
Dec. 23, 2019: FibroGen announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for roxadustat for the treatment of anemia of chronic kidney disease (CKD), in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients.
Roxadustat (FG-4592) is the first orally administered small molecule hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that is submitted to FDA regulatory approval for the treatment of anemia of CKD.
Dec. 23, 2019 : U.S. Food and Drug Administration(FDA) approved Intra-Cellular Therapie’s CAPLYTA® (lumateperone) for the treatment of schizophrenia in adults, commercial launch of CAPLYTA in late Q1 2020.
The efficacy of CAPLYTA 42mg was established in two placebo-controlled trials, showing a statistically noteworthy separation from placebo on the primary endpoint, the Positive and Negative Syndrome Scale (PANSS) total score.
Dec. 23, 2019: Zosano Pharma Corporation announced the submission of a 505(b)(2) New Drug Application (“NDA”) for Qtrypta™ to the U.S. Food and Drug Administration (“FDA”) for acute treatment of the migraine.
This NDA submission represents a considerable milestone for Zosano and a culmination of our efforts to make Qtrypta available to patients who suffer from migraine.
After clinical trials, Qtrypta demonstrated robust freedom from pain and most bothersome symptom, rapid and sustained pain relief for the patients suffering from migraine.
This submission is supported by the results of the ZOTRIP pivotal Phase 2/3 clinical study, in which 41.5% of patients treated with the 3.8 mg dose of Qtrypta achieved pain freedom at 2 hours and 68.3% reported freedom from most inconvenient symptom at 2 hours, both of which were co-primary endpoints.
Qtrypta is Zosano’s proprietary formulation of the zolmitriptan delivered utilizing its proprietary Adhesive Dermally-Applied Microarray (ADAM) technology.
Dec 21, 2019: ViiV Healthcare received a complete response letter (CRL) from the US Food and Drug Administration (FDA) regarding its application for cabotegravir and rilpivirine long-acting regimen for treatment of HIV-1 infection in virologically suppressed adults.
Cabotegravir is an integrase strand transfer inhibitor that is developed by ViiV Healthcare and rilpivirine – non-nucleoside reverse transcriptase inhibitor developed by Janssen Sciences Ireland UC. T
What you need to include in a research paper is ABSTRACT: Now, why is the abstract important?: It essentially seduces the reader into reading the rest of your paper and provide a general understanding about the story inside. An abstract describes about what you do in your essay, whether it’s a scientific experiment or a literary analysis paper. Your abstract must summarize all of the parts of the paper by writing accurately, concisely, and includes only the most important content so that you can keep those readers seduced into reading your paper.
To write an abstract, conclude your paper first, then type a summary that defines the purpose, problem, methods, results, and conclusion of your work. After you get the details down, all that’s left is just to format it correctly. Since an abstract is only a summary of your workdone, so it’s easy to accomplish!
So, before coming to structure of the abstract let’s talk about the couple of things you need to keep in mind before you begin to write it.
Getting your abstract started:
1. Write your paper first: Although an abstract goes at the beginning of the work, it acts as a summary of your entire paper. Put away writing your abstract for last, after you have already finished your paper.
2. Review and try to understand any requirements for writing your abstract. The paper you are writing probably has some specific guidelines and requirements, whether it is for publication in a journal, submission in a class, or part of a work project. Before you start writing, first refer to the guidelines, also about the LENGTH,STYLE and REQUIRENMENTS.
3. Consider your audience. Refer to others persons as guide or mentor just to know, what changes you still have to do.
4. Verify the type of abstract.
Now start writing your Abstract: There are total 5 parts of abstract, as given below. Purpose Problem Method Result conclusion
1. Identify your purpose. The reader wishes to know why your research is important, and what’s the purpose of it. Example: “This study explains about Development and Characterization of the Paclitaxel loaded Riboflavin and Thiamine Conjugated Poly (propylene Imine) Dendrimer mediated brain delivery”
2. Explain the problem. Abstracts state the “problem” behind your work. What problems is your research trying to better understand or solve, also what is the scope , What are your main claim or argument? “Brain tumor is difficult to treat because of poor absorption of many potentially useful antitumor drugs through BBB (blood brain barrier). Present study was aimed for developing and exploring the use of Paclitaxel- loaded Riboflavin and Thiamine Conjugated Poly (propylene Imine) Dendrimer for increase delivery of this drug across BBB.”
3. Explain your methods. Now this is the part where you give an overview of how you gifted your study. If you did your own work then include a description of it or If you reviewed the work of others, it can be explained in few words. “The developed conjugates were characterized using FTIR, NMR spectroscopy, electron microscopy drug loading, release, hemolytic, and ex vivo studies.”
4. Describe your results (informative abstract only). This only for informative abstract, you will be asked to present the results of your study. What you found(results)?, What answer did you attain from your research or study?, Was your theories or argument supported?, and what are the general findings? “The PTX-Tm-PPI and PTX-Rf-PPI showed more cytotoxic effect as compared to PTX and PTX-PPI with PTX-Rf-PPI exhibiting the maximum cytotoxic potential. Biodistribution studies confirmed about the targeting efficiency and higher biodistribution of Tm-PPI conjugates into the brain.”
5. Give your conclusion (in both descriptive and informative abstracts). This should end up your summary and give closing to your abstract. In it, deal with the meaning of your findings as well as the importance of your overall paper. “The result concluded that the riboflavin and thiamine conjugated PPI dendrimer has great potential to deliver significantly higher amount of drug to brain tumor for improved therapeutic outcome.”
Formatting Your Abstract:
1.Keep it in order. Write your abstract in an order like first write introduction, body, and then conclusion. Many journals have specific style guidelines for the abstracts. If you have been given a set of rules or guidelines, follow them to the letter.
2. Provide helpful information. Unlike a topic paragraph, which may be intentionally indefinite, an abstract should provide helpful explanation of your paper and your research. Try to avoid using direct acronyms or abbreviations in the abstract and do not include tables, figures, sources, or long quotations in your abstract. “Brain tumor is difficult to treat because of poor absorption of many potentially useful antitumor drugs through BBB (blood brain barrier). Present study was aimed for developing and exploring the use of Paclitaxel- loaded Riboflavin and Thiamine Conjugated Poly (propylene Imine) Dendrimer for increase delivery of this drug across BBB.”
3. Write it from scratch. Although your abstract is a
summary but it should be written entirely separate from your paper. Don’t just
copy-paste original sentences from paper, also avoid simply paraphrasing your
own sentences, try to write your sentences using completely new vocabulary and
phrases just to keep it interesting.
4. Use key words and phrases. If you want your abstract is to be published in a journal and people should be able to find it easily, then readers will search for definite queries on online databases in hopes that the papers, like yours, will show up. Also, try to use 5-10 important words or phrases key to your research in your abstract. KEY WORDS PPI Dendrimer. paclitaxel. riboflavin. thiamine. Vitamins
5. Use real information. You want to represent people in with your abstract;
it is the hook and eye that will promote them to continue reading your paper.
On the other hand, do not reference ideas or studies that you don’t include in
your paper to do this. Citing material that you don’t use in your work will misinform
readers and ultimately lower your viewership.
6. Avoid being too specific. An abstract is a summary , you should not need to explain or define any terms in your abstract, a reference is all that is needed. Avoid being too explicit in your summary and stick to a very broad overview of your work and avoid terminologies. https://www.ncbi.nlm.nih.gov/pubmed/22994427 https://www.wikihow.com/Write-an-Abstract
What is summarizing: Giving a short statement of the important points by removing all extra fat. Why is it important: It allows you to restate key information in a way that is short and in order.You can be do this amazing summarizing things by using your five fingers in five words or less in less than five minutes method as
WHO-WHAT-WHEN-WHERE-WHY Finger 1. Write WHO was in the story/ article. Finger 2. Write WHAT happened in the story/ article. Finger 3. Write WHEN it happened. Finger 4. Write WHERE it happened. Finger 5. Write WHY it happened. Now completing these, write HOW it happened in five words or less. Now, The Summary Requirements:
Keeping in mind these, you can write your story/ article or Research Paper 1. Brief / concise: it must contain only important points. 2. Paraphrase : change the sentences without changing in the meaning. 3. Skim, Scan, key ideas : Skim (don’t go deep, make it simple and clear), Scan (can read just one min),key ideas(main points). 4. Write using notes: just pull out all the important points and write it in your own words. 5. Combine sentences: combine two or three sentences to make one, just to make it shorter. 6. Same order as passage: order of points must remain same. 7. Use connectives: use and ,or, but to combine sentences. 8. Use topic sentence in paraghraph: wright that one senctence that can tell you full story/ article. 9. Use reporting verbs: when you are writing something, try to use report verbs like beg, admit, point out, demonstrate, examine. 10. Write nice title.
The scope of this blog to give the overview of Drug approval process in US.
The regulatory agency of USA is FDA which has two bodies: CBER and CDER. CBER stands for Centre for biological evolution and Research and CDER stands for Centre for drug evaluation and research. CBER agency deals with biological product whereas CDER deals with drugs and biological both. In general the drug (chemical) approval process in US can be divided into four parts, they are:
Supplemental new drug application
Abbreviated new drug application
Petitioned ANDA
and New drug application
Abbreviated new drug application (ANDA): It follows the 505 b (j) pathway. Proposed drug candidate must be same with respect to following attributes compared to Reference listed drug (RLD). List-1
Active ingredient,
Indication
Dosage strength,
Dosage form,
Route of administration
Inactive ingredients
As per FDA, “A Reference Listed Drug (RLD) is an approved drug product to which new generic versions are compared to show that they are bioequivalent.”
Bio-equivalence studies (to check rate and extent of absorption) are conducted to ensure that proposed product is bio equivalent to RLD. Safety and efficacy studies are not required. Certain differences in inactive ingredients are permissible. Few differences in the inactive ingredients are allowed in ophthalmic, Parenteral and otic formulations. Preservative buffer and antioxidants can differ from the RLD parenteral formulation. These excipients are called exception excipient. The difference in the excipient should not have any effect on safety and efficacy of drugs.
Supplemental new drug application: This application follows the 505(b2) pathways. It can be chosen if a proposed drug candidate has to undergo any of the changes mentioned in list-1. In addition to this, if any switch to OTC product from prescription or any new combination of drugs, are evaluated, then it follows 505 b(2) pathway. If any change in active ingredients as new salt formulation or complex, then FDA can consider it for 505 b(2) pathways .
Petitioned ANDAs (submitted and approved under § 505(j)): As per the FDA: “A petitioned ANDA is a type of ANDA for a drug product that differs from the RLD in its dosage form, route of administration, strength, or active ingredient (in a product with more than 1 active ingredient), and for which the FDA has determined, in response to a suitability petition under § 505(j)(2)(c), that safety and efficacy studies are not necessary for the proposed drug product.” In short, applicants apply for 505 b(2), but FDA determines that safety and efficacy studies are not needed and drug product is reviewed under petitioned ANDA.
NDA (New Drug application): This pathway is used for new chemical entity which has not been approved by the FDA. Rigorous pre-clinical and clinical studies (Phase I to Phase III) are required to establish PK-PD profile, safety and effectiveness of the drug candidate before submission to FDA.
Dec 18, 2019: Pfizer Inc. announced that the U.S. Food and Drug Administration (FDA) has approved priority review to the Company’s supplemental New Drug Application (sNDA) for BRAFTOVI® (encorafenib) in combination with ERBITUX® (cetuximab) (BRAFTOVI Doublet) based on results from the Phase 3 BEACON CRC trial, which evaluated the effectiveness and safety of BRAFTOVI in combination with ERBITUX with or without MEKTOVI® (binimetinib) in patients with advanced BRAFV600E-mutant metastatic colorectal cancer (mCRC), subsequent one or two lines of therapy.
Dec 19, 2019: Galapagos NV announced that its collaboration partner, Gilead Sciences,) has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for filgotinib, an investigational, oral, selective JAK1 inhibitor for the treatment of adult patients living with moderate-to-severe rheumatoid arthritis (RA).
A priority review voucher was submitted with the NDA, shortening the probable time for review. The NDA filing is supported by 52-week data from the global Phase 3 FINCH clinical program, which evaluated the efficiency and safety of filgotinib in 3,452 patients with moderate to severely rheumatoid arthritis.
According to the FINCH studies, filgotinib met its primary endpoints and demonstrated durable effectiveness and safety results across the multiple RA patient populations, including in people with previous inadequate response to methotrexate treatment (MTX), those who were intolerant to one or more biologic treatments and also, those who were MTX treatment-naïve.
Dec 19, 2019: Oxidien Pharmaceuticals, announced that it has received encouraging responses from U.S. Food and Drug Administration (FDA) regarding their proposed Phase 1/2 trial in secondary hyperoxaluria patients and other development plans for its lead drug candidate. The FDA reviewed Oxidien’s IND enabling pre-clinical data, and the results from a prospective, randomized, double-blind, placebo-controlled healthy volunteer study that evaluates both safety and efficacy.
Before this year, Oxidien Pharmaceuticals, LLC, spun out the hyperoxaluria research division from Captozyme Inc., a microbiome contract development and the manufacturing organization.
