Monthly Archives: September 2016

Eteplirsen – Approved for Duchenne Muscular Dystrophy

Today US-FDA gave a fast track approval for Duchenne Muscular Dystrophy (DMD) | Eteplirsen (Exondys 51) | Manufacturer: Sarepta Therapeutics.

Duchenne Muscular Dystrophy:

It is an X-linked neuromuscular diseases typically caused by disrupting the reading frame in the dystrophin (DMD) gene located on Xp21.

The Dystrophin Gene and Its Mutations:

The dystrophin gene is one of the largest known human genes, with a total of 79 exons. Its messenger RNA (mRNA) measures 14 kilobases and takes 16 hours to transcribe. Its large gene size of 2.5 megabases provides a potential explanation for the large number (~4,700) of mutations documented so far.

There are three types of mutations that can disrupt the expression of dystrophin in DMD:

Exon deletions, point mutations, and Duplications.

Exon Deletions: The majority of DMD patients (60%- 70%) carry exon deletions, which cause frameshift mutations and generate non-functional proteins.

Point Mutation: An estimated 25% to 35% of DMD patients have point mutations, which can be further classified as nonsense mutations, small insertions/deletions, and splice site mutations. Nonsense mutations are point mutations that result in a premature termination codon, and accounts for about 12% of disease-causing mutations in DMD patients.

Duplications: Present in approximately 5% of DMD patients, could also lead to frameshift transcripts.

Eteplirsen, an Antisense Oligonucleotide (AON) which triggers excision of exon 51 during pre-mRNA splicing of the dystrophin RNA transcript. Skipping exon 51 changes the downstream reading frame of dystrophin; giving eteplirsen to a healthy person would result in production of dystrophin mRNA which would not code for functional dystrophin protein but, for DMD patients with particular frameshifting mutations, giving eteplirsen can restore the reading frame of the dystrophin mRNA and result in production of functional  dystrophin.It is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13 percent of the population with DMD.

Eteplirsen is given by intravenous infusion for the treatment of DMD. It costs around $300,000 per year, a net price based on patient’s weight.

Exon skipping is induced by Eteplirsen, a charge-neutral, phosphorodiamidate morpholino oligomer (PMO) that selectively binds to exon of dystrophin pre-mRNA, restoring the open reading frame and enabling production of functional, but truncated, dystrophin.The uncharged nature of the PMO helps make it resistant to biological degradation. This truncated dystrophin protein produced by eteplirsen causes a less severe form of dystrophinopathy, much like Becker muscular dystrophy. PMO technology to treat other genotypes amenable to exon skipping to potentially treat an estimated 70 to 80% of all DMD patients with dystrophin gene deletion. Eteplirsen’s proposed mechanism of action is increasing the production of muscle protein. By increasing the quantity of an abnormal, but potentially functional, dystrophin protein, the objective is to slow or prevent the progression of DMD.

Eteplirsen: Mechanism of Action_Exon Skipping

Controversy surrounding its approval:

The FDA granted Etiplirsen fast track designation, which is a designation to facilitate the development and expedite the review of drugs that are intended to treat serious conditions and that demonstrate the potential to address an unmet medical need. It was also granted priority review and orphan drug designation.Priority review status is granted to applications for drugs that, if approved, would be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

FDA approved Etiplirsen based on a study on 8 subjects (boys) with DMD. Two groups, n=4, compared Etiplirsen 30 & 50 mg/kg/wk vs placebo. Read about this study here. This has raised many questions on the approval process.

Read more about the delays in the approval of Etiplirsen here.

Read about the Eteplirsen Briefing document here and about the PI here.

One more drug in the race is: Biomarin’s Drisapersen

Also, if an exon deletion or point mutation still allows for in-frame reading, a truncated but partially functional dystrophin may be expressed, and the patient could present with Becker muscular dystrophy (BMD), a less severe form of muscle dystrophy that is found in three times fewer patients than DMD. A semi-functional dystrophin may be sufficient as Becker patients exhibit milder symptoms and can survive into their 60s.


Extension of Early bird registration & Abstract submission deadline: National Conference on Basic and Clinical Pharmacology, Narayana Medical College, Nellore

Update on our event!

Due to requests from attendees we have extended the EARLY BIRD REGISTRATION (till 30.9.16) and ABSTRACT SUBMISSION DEADLINE (22.9.16). Kindly note down. The organisers have arranged for a Gala dinner (8.9.16), with Dj For8lity dropping some of the best EDM/bollywood tunes!
Also, a reminder that online registrations can be done through:

Don’t miss it!

~ Workshop – Conference – Entertainment ~



The FDC battel continues

The NewDelhi government has moved the Supreme Court in defense of the ban it imposed earlier this year on hundreds of fixed dose combination drugs that it alleged to be irrational, unsafe for patients and lacking scientific validation. Armed with approvals from state regulatory agencies and, in certain cases, the central drug regulator, scores of drug makers countered the decision in courts. Read more here.


Online Registration for National Conference on Basic and Clinical Pharmacology | NMC, Nellore (Social Media Partner) associated PlexusMD for online registration of the National Conference on Basic and Clinical Pharmacology, Nellore.

Click here to register online:



0 Exclusive | Interview with Dr.Madhura Naik

MD Pharmacology graduates can now add one more option for their higher education, apart from joining DM/DNB Clinical Pharmacology or PhD or pursuing a MSc/PG.Dip in foreign universities. Department of Clinical Pharmacology, Tata Memorial Centre Advanced Centre for Treatment, Research and Education in Cancer (TMC-ACTREC) has started a one year fellowship program in Oncotherapeutics.


TMC is an autonomous grant-in-aid institution of the Department of Atomic Energy (DAE), Government of India.

ACTREC is the state-of-the-art R&D satellite of the Tata Memorial Centre (TMC), which also includes under its umbrella the Tata Memorial Hospital (TMH), the largest cancer hospital in Asia. ACTREC has the mandate to function as a national centre for treatment, research and education in cancer. congratulates Dr.Madhura Naik on joining as the first fellow in Oncotherapeutics at TMC-ACTREC. We are happy to have her interviewed. Read what she has told us about this program.

What is this Oncotherapeutic fellowship?

It’s a one-year fellowship program by the Dept. of Clinical Pharmacology held at Tata Memorial Centre- ACTREC, Navi Mumbai for a period of 1 year. This is the first year that they have started the fellowship.

How did you come to know about this? Did “Mumbai Edge” help you in this regard?

I got to know through a colleague on whatsapp first then from the Tata website

Explain the application and selection process.

The application process was online after which candidates were approx. 70 candidates were screened. We had to answer a MCQ exam after which 10 candidates were shortlisted for the interview. The interview was held by a panel comprising clinical pharmacologists, basic researcher and medical oncologist,after which 1 candidate was chosen for the fellowship.

What’s your job profile during the fellowship tenure? How much is your stipend?

The fellowship is actually a fluid program. One can get involved in any of the studies/projects carried out at the department. Here there are multiple research studies in both the preclinical and clinical research areas. ACTREC has a specialized Phase 1 trial unit and multiple trials are ongoing here. The medical management of the trial patients, dosing, monitoring and reporting of ADRs has to be done on a regular basis. Other than clinical trials, there are also teaching responsibilities and opportunity to conduct research studies independently.

  • The stipend is Rs.65,000 per month.

With many medical pharmacologists hunting for jobs at academia or industry or joining DM Clinical Pharmacology, you have decided to join this program. What made you to do so?

I had an interest in oncology drug discovery and development. When I heard about the fellowship I jumped at the opportunity since this is what I always wanted to get involved with.

The common thought process for many MD Pharmacology graduates will be to work abroad. What prospects does this program have for those aspirants?

It may seem enticing as an idea but one has to look at the actual opportunity. Though I know that may people post their training period here have been successful in joining PhD programs in the USA.

Does this give you any edge over your fellow pharmacologists by any means?

I believe that more importantly, it will give me the necessary skill set to further my career in oncology drug development.

After finishing this fellowship, where will you be placed?

I am still figuring this out. It really depends on how I use the 1 year given to me. I would ideally like to get a thorough understanding of all the processes involved in oncology research and then keep my mind open towards opportunities arising in academia or industry.

Does any other hospital or institute offer similar fellowship programs?

To my knowledge, no.

Is this fellowship exclusive to MD pharmacologists?

MD Pharmacologists a well as Pharm D candidates can apply.

Where do you see yourself in future?

I would like to work as a part of an enterprising team of a pharmaceutical company focusing on developing innovative therapies for cancer.

Any suggestions for the MD postgraduate students?

After joining the institute here, I have realized the importance of MD Pharmacologists in drug development. Since we have the right mix of medical acumen and drug therapy knowledge, we can make our presence felt. It is important to focus on developing the right skills in whichever area we are interested in – whether it is pre-clinical research, clinical drug development, regulatory affairs or drug safety/pharmacovigilance.


Dr. Madhura Naik had completed her MBBS from Pad.D.Y.Patil Medical College, Nerul and MD Pharmacology from TNMC Medical College and Nair hospital, Mumbai.  She is kind of a person who focuses on innovation and believes in the maxim -“The only thing that’s constant is change“. Her eagerness to learn and read is not limited to medicine. She loves music, travel and sampling coffees from all over the world.