Race for Gland Pharma

Gland Pharma, a Hyderabad based company which some years back had started its biosimilar portfolio development in terms of small proteins and mAb initial developments is up for sale. Though the company started developing R&D in terms of small protein development but due to financial constraints had to stop biosimilar process development in between.

The recent news is both Baxter, Torrent Pharma (India) and Fosun Pharma (China) have proposed for its acquisition. The interesting part is both Torrent and Fosun are focusing on biosimilar development, Torrent recently launched its Adalimumab Biosimilar under the name of "Adfrar' and Fosun is developing Herceptin Biosimilar which it is planning to launch in 2018. Who ever acquires gland pharma whether its Torrent or Fosun will already have process in place for small molecule Biosimilar development.

Both Torrent and Fosun have sufficient cash in place, but we need to see if any one of them will be able to close the deal.

Oncobiologics

I admire OncoBiologics, though the company is a very late entrant in the biosimilar race but they developed a good portfolio in a span of just 4 years.

At present they are looking for a IPO where in the price ranges will be for USD 11- 13, which is to be listed in NASDAQ by the symbol ONS and i am sure that once their biosimilar products are launched all across globe their share may give around 3-4 times profit in next 6-7 years. I shall hold this company as a long term investor. 

Their most advanced candidates are ONS - 3010, which is a Humira Biosimilar and ONS- 1045 which is Avastin Biosimilar , these products yet to see Phase III. The company at one hand is promoting itself as a cost effective biosimilar  producer company and at the other hand its promoting its state of the art manufacturing process "Biosymphony model".

Why IPO at this point??????

The company was planning to start the PIII trial for ONS 3010 and ONS 1045 in last quarter of 2015 but due to huge cash burn in 2015 at the rate of -292.9%,they went ahead with the IPO so that they can probably go ahead and start their PIII trials latest by Q2 or Q3 2016, and perhaps this year they would start with other products PI trial (I can pull up the information, if required), Thus this IPO will define their path going forward 

The company already have investors and collaborators funding them in different stages for their Biosymphony model  and advising them with regulatory aspects of launching their products in the regulated marker and already partnerships placed all across the globe for their Biosimilar products manufacturing, marketing and sales.

In future i shall not be surprised that this company will be acquisition target for companies like TEVA ....

Roche.....

The Swiss giant has become one of the pioneers in the Biopharma segment.

Companies like Roche have a strong active pipeline in their Phase I/II and the company is constantly exploring the LCM (Life cycle management) of its existing several product franchise (> than $1Bn). The second wave of Biosimilars may effect its immunology portfolio and the third wave its Oncology portfolio, But company has already taken several measure to cope up with the stiff competition from Biosimilars

• If you look at the process development of Biopharmaceutical in terms of mAb development, Roche is continuously evolving its process development of its existing innovative portfolio.
• The company is one of the top companies in terms of R&D investments and at every steps from Drug designing to development and preclinical its increasing its operational efficiency, in terms of better cloning, better per batch yield in terms of pilot scales and production scales and Clinical studies approach 
•  Roche is providing its oncology/immunology products at 35-40% discounted rate in the emerging countries compared to the original price in the developed nations.

So i assume that though Biosimilar developers are developing the mAb's at 40-45% less than the originators price, but innovators like Roche will come up with strategy to manufacture the innovative mAb's at half price compared to the current price of the said innovative mAb manufacturing then i don't think that in future there will be much difference in the pricing of innovator drugs compared to Biosimilar's. Also Physicians all across the globe will still prescribe the innovative drug as they know about their for their long terms benefits, so Biosimilar companies will have hard time to influence the Medicare 

The game is going to be tough for the Biosimilars 

Challenges for Biosimilar Producers in India

Companies in the emerging nations like India were the front runners in the Biosimilar development in terms of small protein molecule development over the last decade. I being a molecular biologist was working on E.coli and Yeast and and i could say cloning of small molecule is much more simple work compared to complex molecules rituximab and infliximab and now the third wave which are one step more complex to develop and produce.

The issues companies in India are facing is that pilot scale production for the mAb sometime cannot be copied the same way in large scale production cycle with various factors taken into consideration, and the complexity in production increases when you move from bacteria, yeast to cell lines, then the per batch yield is also a big hurdle, also the regulatory issues related to the upstream and downstream production in regulated market such as EU and US, thus these companies are first launching their product in semi regulated and non regulated market and then looking for partners or collaborators to design PIII trials in regulated market and further launches

The article which i was reading today they mentioned that companies need to understand the MOA of cell lines, Sometime after understanding how the cell line behaves companies still face issues related to per batch production yield.

And i believe that the approval for the second and third wave of Biosimilars is still going to be difficult as regulators are still developing their understanding of the complexity of these molecules and further their safety and efficacy.

Update on Samsung's Benepali

Samsung Bioepsis and Biogen's Benepali (Enbrel Biosimilar) received approval by EMA on Jan 2016.  Samsung has already launched the European production in UK and the drug has already been launched in  UK, Norway, Germany, and Netherlands. Today Benepali got approval by Danish regulatory authorities and the collaboration expects to capture 50% of the originator market as local hospitals and doctors favor prescribing drugs selected by the procurement agency. Benapali is been sold at 40 to 50% less price compared to the originator.

The collaboration is actively promoting the uptake of Biosimilar all over EU market. Both Samsung Bioepsis and Biogen are enjoying the first mover advantage before the the upcoming European approval for Sandoz Enbrel Biosimilar. 

Samsung Bioepis has gained approval of its biosimilars for Remicade and in future will try to get approval for Roche’s Herceptin, and AbbVie’s Humira Biosimilar. The company has a Phase I clinical trial underway for its Avastin Biosimilar, currently, Bioepis has been  valued at $8 Bn and is trying to be listed on the Nasdaq. Samsung Bioepis has set a target revenue of $872 Mn by 2020.

After Sandoz , we have Daiichi and Coherus Biosciences Enbrel Biosimilar study going on which has met primary end point for PIII trial in Jan 2016 and now regulatory submission has to start. Rest around 8 companies are working on Enbrel Biosmilar, some have received approval in the semi regulated market and we have to see if the approved product in the non regulated and semi regulated market will be going ahead and be part of the second wave of Biosimilars 

The originators meanwhile are reducing Enbrel price at their end and probably will be using their age old bundling approach for drug uptake

Amgen.......ABP 501- More update

Sometime back i had posted about submission for ABP 501. Recently Amgen presented data from a Phase III trial comparing the biologic Humira to its biosimilar ABP 501 at the American Academy of Dermatology meeting in Washington, D.C.

The trial had in total 152 patients on ABP 501 and 79 on Humira,  and they compared the effectiveness of the two drugs for a year. According to the data, results were similar for both the drugs. Comparable numbers of patients had improvement, with about 85% of patients in both groups had experienced a 75% improvement in their psoriasis, and about 40% becoming completely clear.

According to researchers side effects were similar for the two groups too,. About 86% of patients on the biosimilar, and about 79% of patients on the biologic.The most common side effects in both groups included headache, upper respiratory tract infection and the common cold.

What will be Pfizer's next move?????

Last week US treasury Department made a rule change that appeared to be aimed specifically at the transaction of Pfizer and allergan $ 160 Bn deal, stripping Pfizer of its benefits. 

With this deal Pfizer’s would have had relocated its headquarters to Ireland and shaved billions off its tax bill. Pfizer CEO Ian Read said in a brief statement: "We plan to make a decision about whether to pursue a potential separation of our innovative and established businesses by no later than the end of 2016.....

In terms of Biosimilars the question which comes in my mind is that will Pfizer keep the Biosimilar assets of the ongoing program of Allergan and Amgen ABP 215 (avastin Biosmilar) for NSCLC and ABP 980 (Transtuzumab biosimilar) into its own portfolio as its own pipeline PIII studies will be concluded in the later part. 

Also analyst belief that Pfizer will be in acquisition spree again and the target will be companies with attractive assets which may include Shire, Biogen, Regeneron and AbbVie. I believe that Pfizer may go ahead at the earliest for Biogen or Regeneron. In terms of biopharma/biosimilar prescriptive Biogen may be the next best deal for the company. 

After Remicade Biosimilars........the next ones are Adalimumab Biosimilars

Three years back Remicade Biosimiliar was released in EU and this quarter the same Celltrion Biosimilar got approved in US. Now its the turn for Biosimilars for Adalimumab.

As of now Amgen's ABP 501 Phase III trials  are going on  in the European Union and for US positive results for it's phase III trial in arthritis were announced in February 2015. The company has submitted application for approval in  US FDA on November 2015 and to the EMA on December 2015. 

Amgen will have the first mover advantage to market the Biosimilar in both US and EU market, Amgen already has a strong hold in the biological space in both the continents and has been in the part of the lobby which is promoting Biosimilars uptake and approval in the US market for long, so i assume that it will have a better uptake in the US market by 2020 

After Amgen it will be Sandoz and  Boehringer Ingelheim (BI), Germany which will have the second and third mover advantage. Now Abbvie, which has been boasting all about its Humira franchise will not have much affect in its revenue till Q3- Q4 2017 from the First wave of Biosimilars. But from Q2- Q3, 2018 onwards it may feel the heat

And by the time second wave of Biosimilar happens i am sure that Amgen and Sandoz together will capture around as much as 30-35% of the market and BI will have to make its presence felt in the Biosimilar space as it has no credibility till date in Biosimilars

The advantage for both Amgen and Sandoz are that they veterans in the Biologic & Biosimilar space and they are a strong brand themselves and by 2020 they shall have more Biosimilars approved and more Phase 4 study data for their Biosimilars application in various indications , so i assume that Amgen and Sandoz  will be able to capture around 30 to 35% of market..

For BI we have to see how its promoting its Biosimilars by 2020. Also by 2020, we will have more players like Pfizer, Oncobiologics, Fuji (Emerging Markets) coming up as part of second wave for Biosimilar. 

India perspective   we have the Biosimilar for Adalimumab launched in India and i shall capture it in the later parts 

Note:The reason i have provided the ranges between 30- 35% is as per the survey data for Remicade Biosimilar uptake in EU (Data can be skewed thus taken a conservative estimation)

Another Milestone For Emerging Biosimilar Companies

Celltrion received Inflectra (infliximab-dyyb) for multiple indications. Inflectra is administered by intravenous infusion. This is the second biosimilar approved by the FDA. Inflectra is biosimilar to Janssen Biotech, Inc.’s Remicade (infliximab), which was originally licensed in 1998. Inflectra is approved and can be prescribed by a health care professional for the treatment of: -Adult patients and pediatric patients (ages six years and older) with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy; -Adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy; -Patients with moderately to severely active rheumatoid arthritis in combination with methotrexate; -Patients with active ankylosing spondylitis (arthritis of the spine); -Patients with active psoriatic arthritis;adult patients with chronic severe plaque psoriasis. After Positive node from FDA for its safety and efficacy, we were expecting an approval by Q3 2016. This was a pretty fast approval from FDA's end. Also Celltrion is coming up with more Phase 4 data, which i shall be collating in my next update As i track the generic companies in India, i have observed that FDA's has fasten its process both the generic and other approval. Also to note is that Samsung Bioepis (South Korea) has also received recommendation from EMA for its in-development biosimilars: Flixabi, a biosimilar of Janssen’s blockbuster Remicade for Inflammatory diseases.

CMO to Biosimilar developer journey

What is common between Celltrion, Samsung Bioepsis, Biocon and Oncobiologics ??????

All these companies are actively promoting themselves as one of the leading contract manufacturing companies for both Biopharmaceuticals and Biopahrma production and have formed alliances with major companies in the regulated market during Biosimilar drug development process. The first three already have marketed products in regulated market and Oncobiologics which was formed in year 2011 has already finished P1 clinical studies for ONS -3010 (Humira Biosimilar) and ONS- 1045 (Avastin Biosimilar and i assume the said mAb's to enter P3 clinical studies by early 2016

In the span of less than 10 years these companies have evolved as a major biosimilar developer in their specific countries...its a great achievement till now....

Now we need to see how the generic players who have already marketed products  and are developing their Biosimilar portfolio will be evolving as a third party vendor in the developing world for the major Pharma's. Let see how the landscape evolve in the coming years.....

Biocon the game changer for Biosimilar’s from India

Biocon for past sometime is developing its biosimilar portfolio with state of the art Biopharma production unit in India and in Malaysia. Biocon-Mylan Biosimilar’s partnership is progressing well as company is planning to file upto 5 biosimilars in EU and US. In 2014, the company became the first biosimilar company to launch Roche’s Herceptin copycat “Canmab” in India but now it is planning to launch this product along with four other biosimilars which are in development phase.

According to the company latest update  

1.       Insulin Glargine global Phase III trials were completed in the first quarter of this fiscal,

2.       Patient recruitment for multi-centric global Phase III for Pegfilgrastim and Trastuzumab are nearing to their completion while the global Phase III clinical trial for

3.       Adalimumab PIII trial is in progress across multiple sites.

4.       Bevacizumab PI PK studies is approaching completion while the ROW focused Phase III trial is advancing as per plan

Today the company announced that Japanese Ministry of Health, Labour and Welfare (MHLW) has given approval to its insulin Glargine Biosimilar. This approval will give Biocon and its partner, FUJIFILM Pharma, opportunity to bring quality and affordable medicines for diabetes patients in Japan

What surprises me is that Biocon is the late entrant in the Biosimilar space, Dr Reddy’s, Intas and Wockhardt were already in the space last decade in terms of small molecules and mAb’s. What is taking these companies so much time to go ahead for their products launches from semi- regulated to regulated market. 

In 2013 Dr Reddy’s said that it is planning to launch its Bioismilar products in EU in next 5 years. 3 years are already over but it has not yet started PIII clinical trials for the same in the regulated market, what is it doing??

Celltrion's Remsima.......

I have been working in the field of Biosimilars for past 10 years. First in the process of cloning to pilot scale purification process, then later moved into IP and then CI projects for Biosimilars. I am enjoying the way the scenario is changing for the biosimilar in terms of manufacturing, planning of clinical trials and then the over all customer engagement initiatives happening at different company level.

Yesterday FDA's independent committee of 24 members, 21 in favour and 3 in opposition offered opinion on the quality, safety and cost effectiveness of Celltrion’s Remsima Biosimilar. This committee's view will not determine the approval but its opinions will largely influence FDA's decision. Remsima will be used for treatment of rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, psoriasis and psoriatic arthritis.

Some analysts expect Remsima to be introduced in the United States by 2018 but I assume that Remsima will be approved by Q3, 2016 and slow uptake will start happening from Q4 2015 to Q1 2016 onwards. Celltrion has not disclosed what they might charge for Remsima, but a substantial discount is expected. What’s there after Q2, 2017 is to watch for?????