Source : 'Generics Bulletin'
Zydus group's Cadila Healthcare Ltd. hopes to launch its version of Gilead Sciences Inc.’ investigational COVID-19 drug remdesivir in India by end-July, even as other early licensees Cipla Ltd. and Hetero Drugs Ltd. have just introduced the formulation in the country. Marketing approval for Zydus Cadila's brand of remdesivir is expected by mid-July.
Meanwhile, the company’s other COVID-19 candidates - a DNA vaccine and pegylated interferon alpha-2b - are also being fast-tracked.
After receiving approval from the Indian regulator, the Drugs Controller General of India, for clinical trials of pegylated interferon alfa-2b, the company plans to conduct a study in moderate cases of COVID-19 in Mexico and is working on an investigational new drug application for use of the drug in mild cases in the US.
At the forefront of the COVID-19 battle, both by design and default, Cadila is also seen benefiting from the recent pronouncement by the University of Oxford that dexamethasone, a product that Cadila currently produces, lowers mortality in severe cases of COVID-19. ("Dexamethasone Shows Potential Of Repurposed Generics Against COVID-19" "Generics Bulletin" )
“We have a good supply chain [for dexamethasone] and we contribute a large part of the Indian formulations market. We are geared up to supply if the regulator approves the use of the product in India and outside,” managing director Sharvil Patel told Generics Bulletin sister publication Scrip.
A rush for hydroxychloroquine after several countries granted emergency use authorization has already seen the company make moderate gains off exports and increased domestic demand.
Remdesivir has been launched in the Indian market as an injectable to be administered in a hospital setting, a route that Cadila is also likely to take. Meanwhile, Gilead plans to begin testing an inhaled version of the product, hoping that ease of administration will drive increased usage. ("Gilead Ramps Up Remdesivir Manufacturing Advances Inhaled Formulation" "Scrip" )
Gilead initially licensed remdesivir for treating COVID-19 to a set of five companies - Cipla, Hetero, Jubilant Life Sciences Ltd., Mylan NV and Ferozsons Laboratories Ltd. - which was later extended to include Cadila Healthcare, Dr. Reddy's Laboratories Ltd. and Syngene International Ltd.. ("Remdesivir Rivals Hit Indian Market" "Generics Bulletin" )
While short-term advantages from the topsy-turvy world of COVID-19 therapies might continue, the company is focusing on expanding the opportunities for its new chemical entities like desidustat.
A novel oral hypoxia-inducible factor prolyl hydroxylase inhibitor, the molecule is so far under clinical trials for treatment of anemia in chronic kidney disease patients and is being explored in the US for myelodysplastic anemia and chemotherapy-induced anemia.
Aplastic anemia and myelodysplastic syndromes are rare and serious disorders that affect the bone marrow and blood which can be caused by aging, cancer treatments and exposure to chemicals and heavy metals. 16,000 patients in US and 14,000 patients in Japan live with the diseases.
Besides, the possibility of its use for moderate cases of COVID-19 is being evaluated for regulation of levels of iron in the blood of such patients.
Another NCE, saroglitazar magnesium, is moving into Phase III trials in the US. After launching the drug in India to treat non-alcoholic steatohepatitis, the company is readying the protocol and hopes to approach the US Food and Drug Administration during the second quarter, said Patel during a post-earnings call.
It’s not immediately clear if the trials, earlier scheduled for Q2, will begin as planned. ("Zydus Cadila First Off The Block In NASH After India Approval" "Scrip" )
Enrollment in sites across US and Mexico has begun for Evidence VII Phase II clinical trial to evaluate saroglitazar in the treatment of non-alcoholic fatty liver disease in women with polycystic ovary syndrome. The company has also secured approval from the FDA to conduct clinical trials in hepatic impairment in 100 patients and renal impairment in 32 patients.
“These studies will help us understand the pharmacokinetics of saraglitazar in mild, moderate and severe hepatic impairment patients and severe renal impairment patients,” he explained.
The company has also received approval from India's DCGI to initiate Phase I trials for ZYCK-2 and another investigational drug to treat rheumatoid arthritis. Phase I studies for a hepatitis A vaccine are complete while a Phase I program for a recombinant hepatitis E vaccine is underway.
With one of its main contributors to US revenue, Asacol -HD (mesalamine) delayed release tablets for mild to moderate ulcerative colitis, about to run through a 180-day exclusivity, Cadila Healthcare plans to fill the gap by introducing new injectables and transdermals.
The company obtained “first generic” approval in 2017 for Asacol HD and Lialda (another mesalamine product), which permits a manufacturer to market a generic drug in the US - essentially the first generic rival to the reference product - granting it a 180-day exclusivity period. Once this period ends, generics prices generally fall sharply as more players enter the market.
Besides, several more drugs are in the pipeline for moderate to severe ulcerative colitis, including new oral therapies. ("Pfizers Xeljanz Pushed By New Tailwind From Approval In Ulcerative Colitis" "Scrip" )
“In the next one to two years, we will have some very critical launches. We also have very successful in-licensing activity happening so over the next three years we will have around 50 launches of injectables alone,” said Patel.
The company is also capitalizing on shortages caused by COVID-19-led supply chain disruptions as also opportunities arising from the presence of N-Nitrosodimethylamine in sartan products such as valsartan, ranitidine and metformin. ("COVID-19 Demand Gives Lupin Optimism On Albuterol" "Generics Bulletin" )
Price erosion in the US market is down to single digits and the company has also seen margin increases in some cases apart from volume gains, he added.
At the same time, Cadila Healthcare is seeking partners in China for RabiMabs, its monoclonal antibody used to treat rabies. In India, the novel biologic is indicated in combination with rabies vaccine for rabies post-exposure prophylaxis and the company plans to launch it as Twinrab in India in June.
“We are in advance discussions with one of the largest Chinese players for commercializing this product in China,” Patel revealed. His remark points to a “business as usual” sentiment among Indian companies, despite a recent border dispute and related altercations between India and China.
Cadila earlier entered into a licensing agreement with China Medical System Holdings Ltd. to develop and commercialize desidustat in Greater China. ("Asia Deal Watch Chinas BravoVax USbased GeoVax Team Up On Coronavirus Vaccine" "Scrip" )
At the same time, Cadila Healthcare plans to focus on India and emerging markets for its biologics business, having sought regulatory approval of nine to 10 products. It also plans to file for at least four more products over the next three years, with a target of having 12-15 such medicines in its portfolio by 2023.
“The risk is very high, and the costs are very high. So, unless we find a strong enough partner we will not venture there. We will evaluate the second wave of products to see if there is some stabilization and genericization then we will look to nominate some programs” said Patel in response to a question on why the company is leaving developed markets like US and Europe out of its biologics plans.
Seven biosimilar products are in different stages of development, with pre-clinical toxicity studies having been completed for one and initiated for another. Patel said “an array of approvals” are expected for biological products in the coming year. In Russia, approvals for two or three key products are likely by December.
Zydus Cadila said earlier that its Moraiya plant, which has 31 pending abbreviated new drug approvals, would be ready for re-inspection at the end of June 2020. It had received a warning letter from the US FDA.
“We don’t have any concern on an ongoing basis on supply commitments of already approved products. We will finish remediation by end of June with majority of remediation over and we are going to request FDA for a teleconference so we can request for a desktop audit or any form of audit,” said Patel.
The company has already effected transfers of approved injectable products from Moraiya to its Liva facility. ("Levorphanol WriteDown Dents Zydus in Q2 But Saroglitazar Expectations Build" "Scrip" )
The company reported a 18% year-on-year drop in Q4 net profit to INR3.9bn ($51.5m) compared to INR4.6bn for the same period in FY2019. Fourth-quarter consolidated sales for fiscal 2020 were nearly flat at INR37.5bn versus INR37.3bn last financial year.
Impairment charges of INR452m against goodwill in a subsidiary Windlas Healthcare Pvt. Ltd. and INR45m against levorphanol compared to nil last year impacted profits.
Though Cadila Healthcare sold its 51% stake in Windlas Healthcare to Windlas Biotech Pvt. Ltd. after 31 March when Q4 ended, the sale value was lower than carrying value of net assets including goodwill.
This article first appeared in our sister publication, Scrip.
By Vibha Ravi