A weekly podcast highlighting the most important news developments and its impact on the orphan drug, cell and gene therapy world including research advancements, corporate events and regulatory changes.
Special episode: Gene Therapy access from a specialty pharmacy perspective
This episode discusses patient access to AveXis’ gene therapy Zolgensma from Orsini Healthcare, US based specialty pharmacy’s perspective. The senior team at Orsini provide insight on their experience of Zolgensma access including key manufacturer criteria, payer landscape along with challenges and lessons learnt.
Presenter: Aparna Krishnan
Contributors: Dave Frobel, Senior Vice President, Trade & Tom Shaughnessy, Senior Vice President, Health Plans
Producer: Aparna Krishnan
About Orsini Healthcare: Founded in 2009, Orsini is a leading independent specialty pharmacy focused on rare conditions and gene therapies. Orsini was one of the first specialty pharmacies to provide Zolgensma, the first gene therapy for Spinal Muscular Atrophy. Today, Orsini has access to 40 limited distribution drugs, has more than 525 direct payor contracts and is recognized as a reimbursement expert in managing both medical and pharmacy benefits.
Weekly Roundup: February 29, 2020
This week, its a special episode celebrating Rare Disease Day 2020. Our guest speaker is Annie Kennedy, head of policy and advocacy at Every Life Foundation, a US based non profit organisation that works to advance the development of treatment and diagnostic opportunities for rare disease patients through science-driven public policy. Here she speaks about the organisation’s initiatives on drug access.
To know more about the foundation, visit https://everylifefoundation.org/
Presenter and Producer: Aparna Krishnan
Contributor: Annie Kennedy, Chief of Policy & Advocacy, EveryLife Foundation for Rare Diseases
Sponsorships: off
Weekly Roundup: December, 30 2019
As 2019 winds down, P4A’s Sophie Schmitz and Akshay Kumar discuss the key trends that defined this year – marketing approval of cell and gene therapies; pricing and reimbursement challenges in US & EU5 as well as industry merger and acquisitions.
Presenter: Sophie Schmitz
Contributor: Akshay Kumar
Producer: Aparna Krishnan
Weekly Roundup: December, 23 2019
The team discuss the latest update on the proposed EU health technology assessment (HTA) regulation. The key objectives of the 2018 proposal was to promote convergence in HTA tools, procedures and methodologies; reduce duplication of efforts for HTA bodies and industry and improve joint use of outputs. This episode goes indepth into the one of the controversial aspects of the proposal – The joint clinical assessment – that caused a near stand still in negotiations between member states.
Presenter: Christina Poschen
Contributor: Ciaran Cassidy
Producer: Aparna Krishnan
Weekly Roundup: November, 12 2019
The team discuss the NORD summit particularly FDA commissioner Scott Gottleib’s presentation; a panel discussion on cell and gene therapy pricing as well as P4A’s lunch and learn on cell and gene therapy access – learnings from the EU.
Also in this episode, Novartis’ Kymriah innovative payment agreement in Italy, the changing evaluation trends for gene therapies among HTA bodies and Alliance for Regenerative Medicines’ Q3 report.
Presenter: Jack Rawson
Contributor: Sophie Schmitz
Producer: Aparna Krishnan
Weekly Roundup: November, 5 2019
Following an autumn hiatus, the team come back to discuss Vertex’s journey to commercialize Orkambi picking up the story from the latest deal struck with NHS England in October 2019.
Presenter: Nicola Allen
Contributor: Joanna Fernandes
Producer: Aparna Krishnan
Weekly Roundup: January 25, 2019
This week we are looking at the USFDA’s proposed plans to address the expected rise in cell and gene therapy product applications and a significant development in a new controversial procedure called gene drive.
Also, P4A is starting a new campaign that will run throughout February to mark Rare Disease Day. The ‘6P’ campaign is aimed at creating awareness on the impact of rare diseases on key stakeholders and the need for partnership to achieve successful treatment access for patients. The 6Ps are Partnership, Patient, Policy-maker, Physician, Pharma and Payer. P4A will roll out a series of podcast episodes featuring thought leaders representing these stakeholders. So make sure you listen in!
Presenter: Joanna Fernandes
Contributors: Nader Murad and Sophie Schmitz
Producer: Aparna Krishnan
Weekly Roundup: January 18, 2019
This week, the P4A team discusses the Louisiana Medicaid program implementing the ‘Netflix’ subscription model to pay for hepatitis C drugs and the potential Brexit options facing the UK government.
Presenter: Joanna Fernandes
Contributor: Max Rex
Producer: Aparna Krishnan
Weekly Roundup: January 11, 2019
Happy New Year to Weekly Roundup listeners! 2019 is shaping up to be an exciting year for the healthcare and biotechnology industry. We are only a couple of weeks in and already news developments are buzzing on the regulatory and corporate front.
So for this week’s episode, we start by discussing the recent wave of mergers and acquisition deals announced by Big Pharma namely, Eli Lilly and Loxo; BMS and Celgene as well as GSK and Tesaro. Also, the P4A team look at the implications of the current US government shutdown on the FDA and the agency’s initiative on assessments for innovative drugs.
Presenter : Max Rex
Contributor : Joanna Fernandes
Producer: Aparna Krishnan
Weekly Roundup: February 28, 2019
On Rare Disease Day, P4A discusses the role of policy-makers in the healthcare system and specifically, the issues surrounding cross-border healthcare as part of its ‘6P’ campaign.
This directive is a key cornerstone legislation by EU officials that enables patients to find treatment in healthcare facilities outside their home country. However, there are several challenges associated with it.
Presenter: Christina Poschen
Contributor: Dr Andrzej Rys, Director – Health Systems and Products
Producer: Aparna Krishnan
Weekly Roundup: February 22, 2019
In another special edition episode dedicated to the ‘6P’ campaign to mark Rare Disease Day, the Weekly RoundUp team discusses the pharmaceutical perspective on partnerships in the rare disease space.
Presenter: Max Rex
Contributor: Jan-Willem Schmitz, General Manager for Nordics and Baltics, Sanofi Genzyme
Producer: Aparna Krishnan
Weekly Roundup: February 15, 2019
Continuing our special podcast edition marking the annual Rare Disease Day on February 28. The ‘6P’ campaign is aimed at creating awareness on the impact of rare diseases on key stakeholders and the need for partnership to achieve successful treatment access for patients. The 6Ps are Partnership, Patient, Policy-maker, Physician, Pharma and Payer.
This week we focus on the payer who are decision-makers assessing the value of a product in the healthcare system.
Presenter and Producer: Aparna Krishnan
Contributor: Einar Andreassen, senior advisor at the Norwegian Medicines Agency. Einar is a health technology assessment analyst and reimbursement decision maker for the national insurance scheme in Norway.
Weekly Roundup: February 1, 2019
Throughout February 2019, the P4A team are hosting a series of special edition podcast episodes to mark Rare Disease Day. The initiative is part of a new 6P campaign aimed at promoting awareness about rare disease challenges and its impact on people and society. The 6Ps are Partnership, Policy-maker, Payer, Pharma, Physician and Patient. Our message: 6Ps are essential to successfully serve the rare disease community and achieve access to medicines.
This week, we discuss the first P – Partnership. The team reflects on the meaning of partnership in the rare disease context and what it can achieve through examples of different types of collaborations. From patient and clinical experts influencing HTA decisions; key stakeholders coming together for the Hercules Project to a collaboration between US based ICER, Canada’s CADTH and UK’s NICE.
Presenter: Aparna Krishnan
Contributors: Sophie Schmitz, Christina Poschen, Max Rex, Joanna Fernandes, Nader Murad and Jack Rawson
Weekly Roundup: March 28, 2019
The team discuss the creation of a new health economics advisory committee in Spain expected to influence pricing and reimbursement decisions for drugs; and Japan’s approval of its first gene therapy and CAR-T therapy – AnGes’ HGF Plasmid and Novartis’ Kymriah respectively.
Presenter: Joanna Fernandes
Contributor: Max Rex
Producer: Aparna Krishnan
Weekly Roundup: March 22, 2019
This week, we are looking at The Institute for Clinical and Economic Review or ICER’s white paper on alternative options for the US rebate system, and the establishment of a national agency to evaluate drug effectiveness and negotiate prices in Canada.
Presenter: Max Rex
Contributor and Producer: Aparna Krishnan
Weekly Roundup: March 15, 2019
This week, we look at Ireland’s access to orphan drugs as compared to rest of western Europe and the first outcomes deal for CAR-T cell therapies in Germany.
Presenter: Joanna Fernandes
Contributors: Nader Murad, Ciaran Cassidy
Producer: Aparna Krishnan
Weekly Roundup: March 8, 2019
This week, the P4A team discuss the spate of mergers and acquisitions involving Big Pharma companies in the gene therapy space. Particularly, we looked at the deals behind Roche’s acquisition of Spark Therapeutics and Biogen’s buyout of Nightstar. Also, Vertex’s continued struggle to get its cystic fibrosis drug Orkambi reimbursed in the UK.
Presenter: Joanna Fernandes
Contributor and Producer: Aparna Krishnan
Weekly Roundup: April 27, 2019
This week, we look at the European Federation of Pharmaceutical Industries and Associations or EFPIA’s patient wait survey and its key findings as well as news developments in the spinal muscular atrophy world relating to gene therapy Novartis’ Zolgensma and Biogen’s Spinraza.
Presenter : Aparna Krishnan
Contributors: Sophie Schmitz, Jack Rawson
Producer: Aparna Krishnan
Weekly Roundup: April 22, 2019
As part of the continuing World Orphan Drug Congress (WODC) special, this episode discusses the cGMP facilities and biosafety solutions from Germfree’s Carol Houts, P4A’s Sophie Schmitz looks back at the 2019 conference and Terrapinn’s Andre Singer talks about what to expect from WODC 2020.
Presenter : Aparna Krishnan
Contributor: Carol Houts, Director of Regulatory and Quality, Germfree; Sophie Schmitz, Managing Partner, Partners4Access and Andre Singer, General Manager for World Orphan Drug Congress USA, Terrapinn
Producer: Aparna Krishnan
Weekly Roundup: April 12, 2019
This week, the P4A team are podcasting from the World Orphan Drug Congress in Washington D.C. We speak to André Choulika, Chairman and CEO of Cellectis on the challenges of commercializing a CAR-T cell product and ethical concerns surrounding it, and Anna Bucsics from the Mechanism of Coordinated Access to Orphan Medicinal Products (MoCA) on their work supporting new biotech entrepreneurs.
Presenter: Joanna Fernandes
Contributor: André Choulika, Chairman and CEO of Cellectis; Anna Bucsics, Project Advisor to MoCA and Sophie Schmitz, Managing Partner, P4A
Producer: Aparna Krishnan
Weekly Roundup: May 25, 2019
In this episode, we discuss Novartis CEO Vas Narasimhan calling for a change in the US drug payment systems, arguing for new economic models to identify how much value a cure represents. Also, Italy’s attempts at introducing a draft resolution to improve transparency in drug pricing at the World Health Assembly.
Presenter: Aparna Krishnan
Contributors: Joanna Fernandes, Christina Poschen
Producer: Aparna Krishnan
Weekly Roundup: May 18, 2019
This week, the team discuss the deal between UK’s National Health Service and Biogen prompting the successful reimbursement of Biogen’s Spinraza as a treatment for spinal muscular atrophy and Solid Biosciences’ clinical update on its Duchenne Muscular Dystrophy gene therapy product SGT-001.
Presenter : Aparna Krishnan
Contributor: Max Rex
Producer: Aparna Krishnan
Weekly Roundup: May 12, 2019
This week, the P4A team discuss a new experimental therapy – Phage therapy or genetically engineered phages in order to treat bacterial infections and the acquisition of Theracon by Big Pharma firm Pfizer for upto $810 million.
Presenter : Aparna Krishnan
Contributor: Ciaran Cassidy
Producer: Aparna Krishnan
Weekly Roundup: May 3, 2019
This week, we feature a special guest podcast speaker – Scott Dorfman, chief executive officer of non-profit gene therapy developer Odylia Therapeutics on his personal journey and the future in gene therapy development.
If you would like to know more about Odylia Therapeutics, please visit https://odylia.org/
Presenter : Aparna Krishnan
Contributors: Scott Dorfman, CEO, Odylia Therapeutics
Producer: Aparna Krishnan
Weekly Roundup: June 23, 2019
This week, we analyze Bluebirdbio’s commercialization plans for its gene therapy Zynteglo including the new payment model and a delay in launch due to manufacturing issues.
Presenter: Aparna Krishnan
Contributors: Joanna Fernandes
Producer: Aparna Krishnan
Weekly Roundup: June 16, 2019
This week, the team discuss the emergence of ‘drug buyer’s clubs’ in the UK involving Vertex’s cystic fibrosis drug Orkambi.
Presenter: Aparna Krishnan
Contributors: Sophie Schmitz, Ciaran Cassidy
Producer: Aparna Krishnan
Weekly Roundup: June 12, 2019
This week, the team discuss Vertex’s acquisition of Exonics and expansion of its collaboration with CRISPR Therapeutics. Also, we take an indepth look at the European Medicines Agency’s approval of Bluebirdbio’s gene therapy Zynteglo as a treatment for beta-thalassemia.
Presenter: Aparna Krishnan
Contributor: Jack Rawson
Producer: Aparna Krishnan
Weekly Roundup: June 3, 2019
On our anniversary episode, the P4A team discuss the USFDA approval of Novartis’ Zolgensma, a one time gene therapy for paediatric spinal muscular atrophy patients and a look back at the last 12 months of our podcasting journey.
Presenter: Joanna Fernandes
Contributor: Christina Poschen, Aparna Krishnan
Producer: Aparna Krishnan
Weekly Roundup: July 29, 2019
The team takes a look at the most recent legislation in Germany known as GSAV or the law for more safety in the supply of pharmaceuticals and its implications on the access to orphan drugs. GSAV was approved by the German cabinet on January 30, 2019 and is due to come into effect in August this year.
Presenter: Akshay Kumar
Contributor: Joanna Fernandes
Producer: Aparna Krishnan
Weekly Roundup: July 22, 2019
This week, the P4A team discuss the coverage of Novartis’ Zolgensma in the US in particular how US health insurers have received the gene therapy. Also on the agenda was the impact of Zolgensma’s launch on rival Biogen’s Spinraza and the potential for dominance of the gene therapy in the spinal muscular atrophy landscape.
Presenter: Aparna Krishnan
Contributor: Max Rex
Producer: Aparna Krishnan
Weekly Roundup: July 1, 2019
The debate over US drug pricing reform has reached fever pitch as the US Department of Health and Human Sciences announced its latest Medicare Part B proposal to include international reference pricing. The Partners4Access team looks at the background to this proposal; the political and patient organisation criticisms; the potential industry response and its ramifications.
Presenter: Aparna Krishnan
Contributor: Max Rex
Producer: Aparna Krishnan
2018 Podcasts Archive
Weekly Roundup: May 31, 2018
In its very first podcast of Rare Diseases Weekly RoundUp, P4A discusses the US FDA’s accelerated regulatory process for gene therapy; President’s Trump’s proposed drug pricing plan; the European Commission’s proposal to amend SPC; the NHS England budget ringfencing; Irish government’s attempt to trim the HSE and the new GDPR laws. Max Rex hosts with contributions from Aparna Krishnan, Corporate Affairs Lead and Alison Kneen, Vice President, International Operations.
Weekly Roundup: June 26, 2018
This week, the P4A team delve into the pharma industry’s proposal to the EU on the role of national HTA bodies post harmonization of clinical assessments for innovative drug technologies; the European Medicines Agency’s new portal for orphan drug designation applications and Ireland’s entry into the Beneluxa Initiative.
Presenter: Joanna Fernandes
Contributor: Aparna Krishnan
Weekly Roundup: June 19, 2018
The P4A team give a summary of the gene therapy FDA news this week and also discuss President Trump’s drug pricing plans for Medicare as well as UK cost watchdog NICE’s rejection of Crysvita.
Presenter: Max Rex
Contributors: Aparna Krishnan, Joanna Fernandes
Weekly Roundup: June 12, 2018
This week’s episode discusses the EU’s research and innovation budget; Italy’s AIFA responding to physician criticism of new guidelines and Oxford Biomedica’s $842 million deal with Axovant Sciences.
Presenter: Max Rex
Contributors: Aparna Krishnan and Joanna Fernandes
Weekly Roundup: June 5, 2018
This week, the P4A team discuss key advancements in oncology treatments – a genetic test indicating whether chemotherapy is beneficial in a particular breast cancer patient group and successful result of an immunotherapy using T cells in an advanced breast cancer patient. In addition, news involving a potential new sickle cell therapy under development.
Presenter: Max Rex
Contributors: Alison Kneen and Aparna Krishnan
Weekly Roundup: July 26, 2018
The EU’s Commissioner for Competition Margrethe Vestager, recently said that price differences in the pharma market among different member states could be “justified”. This week, P4A delves deeper into the mechanics of drug pricing in Europe including discussing the impact of parallel trade and comparing it to U.S. pricing.
Presenter: Max Rex
Contributor: Stuart Tutt
Presenter: Max Rex
Contributor: Stuart Tutt
Weekly Roundup: July 17, 2018
The U.S. FDA’s new guidance on gene therapy was recently announced by FDA Commissioner Dr. Scott Gottlieb, the P4A team discuss key implications of these guidelines along with an update on UK’s Brexit Whitepaper and new measures by the French government to improve patient access to innovative drugs.
Presenter: Joanna Fernandes
Contributors: Christina Poschen & Aparna Krishnan
Presenter: Joanna Fernandes
Contributors: Christina Poschen & Aparna Krishnan
Weekly Roundup: July 11, 2018
This week, the team discuss the U.S. Centres for Medicare & Medicaid Services withdrawing support for a novel payment model for Novartis’ Kymriah; Pfizer rolling back drug price rise in the U.S. and Axovant’s deal with Benitec Biopharma.
Presenter: Joanna Fernandes
Contributor: Aparna Krishnan
Presenter: Joanna Fernandes
Contributor: Aparna Krishnan
Weekly Roundup: July 4, 2018
This week, the P4A team discuss the CHMP approval of two CAR-T Therapies; Scotland’s new rules for ultra-orphan drugs and the reaction to the announcement of National Coverage Analysis for CAR-T drugs in the U.S.
Presenter: Max Rex
Contributors: Sophie Schmitz & Alison Kneen
Presenter: Max Rex
Contributors: Sophie Schmitz & Alison Kneen
Weekly Roundup: August 16, 2018
In this episode, the team discuss UK health technology body NICE not recommending Biogen’s Spinraza for routine use in the NHS; CVS announcing the use of ICER’s cost effectiveness analysis to decide formulary inclusions and Express Scripts is in talks with several pharma companies for exclusive distribution rights to sell their upcoming gene therapies.
Presenter: Max Rex
Contributor: Aparna Krishnan
Presenter: Max Rex
Contributor: Aparna Krishnan
Weekly Roundup: August 9, 2018
In this episode, the team discusses the UK government’s publication of four key documents guiding the life science industry on how to operate during the Brexit transition period, Spark Therapeutics’ clinical data for its gene therapy treating heamophila A patients and finally, the Irish government plans to reform the country’s healthcare system.
Presenter: Joanna Fernandes
Contributor: Aparna Krishnan
Presenter: Joanna Fernandes
Contributor: Aparna Krishnan
Weekly Roundup: August 2, 2018
This week, the team discuss the consolidation among small and medium sized cell and gene therapy companies and the latest on Brexit impact with news that Sanofi is stockpiling drugs.
Presenter: Max Rex
Contributor: Aparna Krishnan
Presenter: Max Rex
Contributor: Aparna Krishnan
Weekly Roundup: September 27, 2018
This week, P4A’s podcast will cover Luxturna’s CHMP recommendation, Novartis’ restructuring plans and Alexion’s acquisition of Syntimmune.
Presenter: Max Rex
Contributor: Aparna Krishnan
Presenter: Max Rex
Contributor: Aparna Krishnan
Weekly Roundup: September 20, 2018
Back from a summer break! The P4A team discuss the reasons behind NICE’s rejection of Novartis’ CAR-T therapy Kymriah, Denmark and Norway’s joint drug purchasing agreement and US patient groups pushing back against ICER’s influence in drug reimbursement.
Presenter: Max Rex
Contributor: Aparna Krishnan
Presenter: Max Rex
Contributor: Aparna Krishnan
Weekly Roundup: October 25, 2018
This week, we look at Biogen’s spinal muscular atrophy drug Spinraza’s prospects in the face of emerging competition and the latest Brexit update providing recommendations on areas to prepare for as deadline for UK’s exit looms.
Presenter: Aparna Krishnan
Contributor: Joanna Fernandes
Presenter: Aparna Krishnan
Contributor: Joanna Fernandes
Weekly Roundup: October 18, 2018
This week, the P4A team analyse the new regulations surrounding health technology assessments in Europe and US-based CAR-T start-up Allogene Therapeutic’s record-breaking initial public offering.
Presenter: Max Rex
Contributor: Christina Poschen, Consultant, P4A
Presenter: Max Rex
Contributor: Christina Poschen, Consultant, P4A
Weekly Roundup: October 11, 2018
The P4A team analyze Novartis’ deal with Celluar Biomedicine Group to supply the CAR-T therapy Kymriah and the successes and failures of the reimbursement of Vertex’s cystic fibrosis drug, Orkambi.
Presenter: Max Rex
Contributor: Nader Murad, Senior Analyst
Presenter: Max Rex
Contributor: Nader Murad, Senior Analyst
Weekly Roundup: October 5, 2018
This week, Pfizer’s Matthew Harold joins us to discuss the findings of his recent research study that reviewed national policies for rare diseases in the context of key patient needs.
Presenter: Max Rex
Contributor: Matthew Harold, International Developed Markets Public Affairs Lead, Pfizer
Presenter: Max Rex
Contributor: Matthew Harold, International Developed Markets Public Affairs Lead, Pfizer
Weekly Roundup: November 30, 2018
This week’s episode looks at the proposed rules by the Centres for Medicare and Medicaid Services (CMS) in a bid to reduce drug prices and improve e-prescribing and the OECD’s new report on access to medicines.
Presenter: Aparna Krishnan
Contributor: Jack Rawson
Weekly Roundup: November 23, 2018
The P4A team discuss the latest update on Brexit and its implication on life science companies; Novartis’ CAR-T therapy commercialization efforts and the Hercules Project, a unique initiative supporting new drug reimbursements in Duchenne Muscular Dystrophy.
Presenter: Aparna Krishnan
Contributors: Joanna Fernandes and Sophie Schmitz
Weekly Roundup: November 15, 2018
In the second part of our World Orphan Drug Congress special, P4A’s Sophie Schmitz speaks to Diane Kleinermans, adviser to the Belgian Federal Government on the origins and future of the Beneluxa initiative.
Presenter: Aparna Krishnan
Contributors: Sophie Schmitz, Managing Partner, P4A and
Diane Kleinermans, Adviser to the Ministry of Health and Social Affairs, Belgium
Weekly Roundup: November 9, 2018
In the first of a two-part special, the P4A team are at the World Orphan Drug Congress in Barcelona discussing access to new treatments with a Porphyria patient; hear from a company offering a unique service to clinical trial patients; a special interview with Ségolène Aymé on rare disease challenges and a chat with organisers of the congress.
Presenter: Aparna Krishnan
Contributors: Sophie Schmitz, Managing Partner, P4A; Dr Jasmin Burman-Aksözen, Vice President of International Porphyria Patient Network; Helen Springford, Vice President, Illingworth Research Group; Prof Ségolène Aymé, Founder of Orphanet; Andrew Mears, Business Development Manager at Terrapinn.
Weekly Roundup: November 2, 2018
The team analyze the new Medicare drug pricing plan unveiled by the Trump administration and the prospects of Vertex’s cystic fibrosis drug Symkevi which gained EU approval recently.
Presenter: Aparna Krishnan
Contributors: Max Rex and Jack Rawson
Presenter: Aparna Krishnan
Contributors: Max Rex and Jack Rawson
Weekly Roundup: December 14, 2018
In the last episode of 2018, the P4A team look back at the events of the year and particularly on how their predictions on key trends in the rare disease space have fared.
Presenter: Aparna Krishnan
Contributors:
Mergers and acquisitions – Sophie Schmitz
Rare oncology drug approvals – Joanna Fernandes
Future of new technologies like gene therapies – Christina Poschen
Increasing prominence of societal burden data – Nader Murad
Emphasis on planning Real World Evidence – Aparna Krishnan
U.S drug prices – Max Rex
The Weekly RoundUp team will be back in the new year.
Weekly Roundup: December 7, 2018
This week, the team discuss Novartis’ AVXS-101 FDA application; the UK regulators’ promise to review its HTA system under a new voluntary pricing and access scheme and clinical trial updates from bluebirdbio’s gene therapy LentiGlobin.
Presenter: Joanna Fernandes
Contributor: Aparna Krishnan