Catalyst Pharmaceuticals

Catalyst Pharmaceuticals is a biopharmaceutical company based in Coral Gables, Florida. The company is developing therapeutics for rare neurological diseases, including the phosphate salt of amifampridine for the treatment of Lambert–Eaton myasthenic syndrome (LEMS) under the trade name "Firdapse" which was approved by the United States Food and Drug Administration (FDA) for use in Adult LEMS patients on November 28, 2018 and commercially launched in January of 2019.[3][4] On February 4, 2019, Bernie Sanders, United States Senator from Vermont, requested an explanation—including financial and non-financial information—from Catalyst that would justify Catalyst resetting Firdapse's list price at $375,000 a year. Prior to the FDA approval, patients were able to get an experimental version of the drug for free through compassionate use programs in accordance with FDA Rules and Guidelines.[5][6][7]

Catalyst Pharmaceutical Partners, Inc.
Public company
Traded asNASDAQ: CPRX
Russell 2000 Component
IndustryBiotechnology
Headquarters
Coral Gables, Florida
,
United States
Key people
Patrick J. McEnany, co-founder, chairman, president and chief executive officer
ProductsFirdapse® (amifampridine) Tablets 10 mg (commercialized 2019)
RevenueUS$ 0 million (2018)[1] [2]
US$ -35 million (2018)[2]
Total assetsUS$ 60.5 million (2018)[2]
Total equityUS$ 50.2 million (2018)[2]
Number of employees
51 as of March 14, 2019[2]
Websitewww.catalystpharma.com
Footnotes / references
[1] [2]

History

Catalyst was founded in 2002, and completed an IPO in 2006.[8] It focused primarily on developing therapies to prevent addiction until 2012.[9]

In 2009, Catalyst in-licensed worldwide rights to a family of GABA inhibitors including CPP-115 from Northwestern University.[10][11] In 2012, it in-licensed patents covering the use of amifampridine phosphate to treat LEMS for the North American market from BioMarin.[12]

In 2018, Catalyst terminated its license for CPP-115 with Northwestern and stopped the development program for that compound.[13]

History of amifampridine

The development of amifampridine and its phosphate has brought attention to orphan drug policies that grant market exclusivity as an incentive for companies to develop therapies for conditions that affect small numbers of people.[14][15][16]

Amifampridine, also called 3,4-DAP, was discovered in Scotland in the 1970s, and doctors in Sweden first showed its use in LEMS in the 1980s.[17]

In the 1990s, doctors in the US, on behalf of Muscular Dystrophy Association, approached a small family-owned manufacturer of active pharmaceutical ingredients in New Jersey, Jacobus Pharmaceuticals, about manufacturing amifampridine so they could test it in clinical trials. Jacobus did so, and when the treatment turned out to be effective, Jacobus and the doctors were faced with a choice — invest in clinical trials to get FDA approval or give the drug away for free under a compassionate use program to about 200 patients out of the estimated 1500-3000 LEMS patients in the U.S.. Jacobus elected to give the drug away to this subset of LEMS patients, and did so for about twenty years.[18][19][20]

Doctors at the Assistance Publique – Hôpitaux de Paris had created a phosphate salt of 3,4-DAP (3,4-DAPP), and obtained an orphan designation for it in Europe in 2002.[21] The hospital licensed the intellectual property on the phosphate form to the French biopharma company OPI, which was acquired by EUSA Pharma in 2007,[22] and the orphan application was transferred to EUSA in 2008.[21] In 2008 EUSA submitted an application for approval to market the phosphate form to the European Medicines Agency under the brand name Zenas.[23] EUSA, through a vehicle called Huxley Pharmaceuticals, sold the rights to 3,4-DAPP to BioMarin in 2009,[24] the same year that 3,4-DAPP was approved in Europe under the new name Firdapse.[21]

The licensing of Firdapse in 2010 in Europe led to a sharp increase in price for the drug. In some cases, this has led to hospitals using an unlicensed form rather than the licensed agent, as the price difference proved prohibitive. BioMarin has been criticized for licensing the drug on the basis of previously conducted research, and yet charging exorbitantly for it.[25] A group of UK neurologists and pediatricians petitioned to prime minister David Cameron in an open letter to review the situation.[26] The company responded that it submitted the licensing request at the suggestion of the French government, and points out that the increased cost of a licensed drug also means that it is monitored by regulatory authorities (e.g. for uncommon side effects), a process that was previously not present in Europe.[27] A 2011 Cochrane review compared the cost of the 3,4-DAP and 3,4-DAPP in the UK and found an average price for 3,4-DAP base of £1/tablet and an average price for 3,4-DAP phosphate of £20/tablet; and the authors estimated a yearly cost per person of £730 for the base versus £29,448 for the phosphate formulation.[28][29]

Meanwhile, in Europe, a task force of neurologists had recommended 3,4-DAP as the firstline treatment for LEMS symptoms in 2006, even though there was no approved form for marketing; it was being supplied ad hoc.[23]:5[30] In 2007 the drug's international nonproprietary name was published by the WHO.[31]

In the face of the 7 year exclusivity that an orphan approval would give to Biomarin, and of the increase in price that would accompany it, Jacobus began racing to conduct formal clinical trials in order to get approval for the free base form before BioMarin; its first Phase II trial was opened in January 2012.[32]

In October 2012, while BioMarin had a Phase III trial ongoing in the US, it licensed the US rights to 3,4-DAPP, including the orphan designation and the ongoing trial, to Catalyst Pharmaceuticals.[33] Catalyst anticipated that it could earn $300 to $900 million per year in sales at peak sales for treatment of people with LEMS and other indications, and analysts anticipated the drug would be priced at around. $100,000 in the US.[17] Catalyst went on to obtain a breakthrough therapy designation for 3,4-DAPP in LEMS in 2013,[4] an orphan designation for congenital myasthenic syndromes in 2015[34] and an orphan designation for myasthenia gravis in 2016.[35]

In August 2013, analysts anticipated that FDA approval would be granted to Catalyst in LEMS by 2015.[4]

In October 2014, Catalyst began making available under an expanded access program.[36]

In March 2015 Catalyst obtained an orphan designation for the use of 3,4-DAPP to treat of congenital myasthenic syndrome.[37] In April 2015, Jacobus presented clinical trial results with 3,4-DAP at a scientific meeting.[19]

In December 2015 a group of 106 neuromuscular doctors who had worked with both Jacobus and BioMarin/Catalyst published an editorial in the journal, Muscle & Nerve, expressing concern about the potential for the price of the drug to be dramatically increased should Catalyst obtain FDA approval, and stating that 3,4-DAPP represented no real innovation and didn't deserve exclusivity under the Orphan Drug Act, which was meant to spur innovation to meet unmet needs.[17][38] Catalyst responded to this editorial with a response in 2016 that explained that Catalyst was conducting a full range of clinical and non-clinical studies necessary to obtain approval in order to specifically address the unmet need among the estimated 1500-3000 LEMs patients since about 200 were receiving the product through compassionate use – and that this is exactly what the Orphan Drug Act was intended to do: deliver approved products to orphan drug populations so that all patients have full access.[39]

In December 2015 Catalyst submitted its new drug application to the FDA,[40] and in February 2016 the FDA refused to accept it, on the basis that it wasn't complete and in April 2016 the FDA told Catalyst it would have to gather further data.[41][14] Catalyst cut 30% of its workforce, mainly from the commercial team it was building to support an approved product, to save money to conduct the trials.[42] In March 2018 the company re-submitted its NDA.[43] The FDA approved amifampridine for the treatment of adults with Lambert-Eaton myasthenic syndrome on November 29, 2018.[44]

In February 2019, U.S. Senator Bernie Sanders questioned the high price ($375,000) charged by Catalyst Pharmaceuticals for Firdapse.[45][46]

In May 2019 the privately held US company Jacobus Pharmaceutical, Princeton, New Jersey gained approval by the FDA for amifampridine tablets (Ruzurgi) for the treatment of LEMS in patients 6 to less than 17 years of age. This is the first FDA approval of a treatment specifically for pediatric patients with LEMS. Firdapse is only approved for use in adults.[47] Although Ruzurgi has been approved for pediatric patients, this approval makes it possible for adults with LEMS to get the drug off-label. Jacobus Pharmaceutical had been manufacturing and giving it away for free since the 1990s. The FDA decision dropped the stock of Catalyst Pharmaceuticals. The company's stock price has dropped about 50%.[48]

Criticism

On February 4, 2019, Bernie Sanders, United States Senator from Vermont, publicly sent a letter to Catalyst asking why they raised the price of their drug Firdapse to an annual cost of $375,000, considering Firdapse was previously free of charge through an FDA compassionate use program . Sanders questioned the financial decision with regards to the negative impact, specifically asking about how many patients would suffer or die, for patients who may no longer be able to afford the drug. The drug is used to treat Lambert–Eaton myasthenic syndrome (LEMS), which is a rare neuromuscular disorder.[7] Prior to the price change, patients were able to get the drug for free through a U.S. Food and Drug Administration (FDA) compassionate use program.[7][49]

gollark: Did you know? The sun is a shiny potato. It is not, however, a deadly laser.
gollark: ++magic py```es = bot.get_guild(346530916832903169)c = es.get_channel(348698124371361793)return f"#{c.name} \n*{c.topic}*\nPosition: {c.position}\nSlowmode: {c.slowmode_delay}\nLast message: {c.last_message_id}\nOverwrites: {[f'{await es.get_role(int(o.type.split("(")[1].split(")")))}({o.id}): {o.allow} :white_check_mark: {o.deny} :negative_squared_cross_mark:' for o in c._overwrites]}\n{(await c.fetch_message(c.last_message_id)).content}"```
gollark: ++magic py```c = bot.get_guild(346530916832903169).get_channel(348698124371361793)return dir(c._overwrites[0])#return f"#{c.name} \n*{c.topic}*\nPosition: {c.position}\nSlowmode: {c.slowmode_delay}\nLast message: {c.last_message_id}\nOverwrites: {[f'{o.role.name}({o.id}): {o.allow} :white_check_mark: {o.deny} :negative_squared_cross_mark:' for o in c._overwrites]}\n{(await c.fetch_message(c.last_message_id)).content}"```
gollark: ++magic py```c = bot.get_guild(346530916832903169).get_channel(348698124371361793)return f"#{c.name} \n*{c.topic}*\nPosition: {c.position}\nSlowmode: {c.slowmode_delay}\nLast message: {c.last_message_id}\nOverwrites: {[f'{o.role.name}({o.id}): {o.allow} :white_check_mark: {o.deny} :negative_squared_cross_mark:' for o in c._overwrites]}\n{(await c.fetch_message(c.last_message_id)).content}"```
gollark: ++magic py```c = bot.get_guild(346530916832903169).get_channel(348698124371361793)return f"#{c.name} \n*{c.topic}*\nPosition: {c.position}\nSlowmode: {c.slowmode_delay}\nLast message: {c.last_message_id}\nOverwrites: {[f'{o.name}({o.id}): {o.allow} :white_check_mark: {o.deny} :negative_squared_cross_mark:' for o in c._overwrites]}\n{(await c.fetch_message(c.last_message_id)).content}"```

References
  1. "Catalyst Pharmaceuticals 2014 Annual Report Form (10-K)" (XBRL). United States Securities and Exchange Commission. Retrieved March 5, 2015.
  2. "Catalyst Annual Report 2018". ir.catalystpharma.com.
  3. "Firdapse FDA Approval Letter" (PDF). fda.gov. November 28, 2018.
  4. Baker DE (November 2013). "Breakthrough Drug Approval Process and Postmarketing ADR Reporting". Hospital Pharmacy. 48 (10): 796–8. doi:10.1310/hpj4810-796. PMC 3859287. PMID 24421428.
  5. Commissioner, Office of the (May 6, 2019). "Expanded Access". FDA. Retrieved December 9, 2019.
  6. "NDA for Catalyst's LEMS Therapy Firdapse Accepted with Priority Review". Lambert-Eaton News. June 4, 2018. Retrieved December 9, 2019.
  7. Abutaleb, Yasmeen (February 4, 2019). "Senator Sanders asks why drug, once free, now costs $375k". Reuters. Retrieved February 5, 2019.
  8. "Catalyst Pharmaceuticals Registration Statement Form S-1" (XBRL). United States Securities and Exchange Commission. Retrieved September 8, 2015.
  9. Mann Jr., Joseph A. (July 18, 2015). "The big gamble: Catalyst Pharmaceuticals of Coral Gables bets on new drug for rare disease". Miami Herald.
  10. Hawker D. and R. Silverman. “Synthesis and evaluation of novel heteroaromatic substrates of GABA Aminotransferase”, Bioorganic & Medicinal Chemistry, October 1, 2012. Retrieved September 8, 2015.
  11. Brian Bandell. “Catalyst Pharmaceutical signs licensing deal with Northwestern” “South Florida Business Journal”, August 31, 2009. Retrieved September 8, 2015.
  12. “Catalyst Acquires Late-Stage Orphan Drug from BioMarin, “Genetic Engineering and Biotechnology News, November 1, 2012. Retrieved August 27, 2015.
  13. "Catalyst Pharmaceuticals 2018 Annual Report".
  14. Tavernise, Sabrina (February 17, 2016). "F.D.A. Deals Setback to Catalyst in Race for Drug Approval". New York Times.
  15. Drummond, M; Towse, A (May 2014). "Orphan drugs policies: a suitable case for treatment". The European Journal of Health Economics : HEPAC : Health Economics in Prevention and Care. 15 (4): 335–40. doi:10.1007/s10198-014-0560-1. PMID 24435513.
  16. Lowe, Derek (October 21, 2013). "Catalyst Pharmaceuticals And Their Business Plan". In the Pipeline.
  17. Deak, Dalia (February 22, 2016). "Jacobus and Catalyst Continue to Race for Approval of LEMS Drug". Bill of Health.
  18. Silverman, Ed (April 5, 2016). "A family-run drug maker tries to stay afloat in the Shkreli era". STAT News.
  19. "Jacobus Pharmaceuticals". Drug R&D Insight. April 25, 2015.
  20. "BioMarin licenses North American rights to rare disease drug, invests $5M in Florida company". www.bizjournals.com. Retrieved December 17, 2019.
  21. "Public summary of opinion on orphan designation" (PDF). EMA. June 14, 2010.
  22. Chapelle, François-Xavier (November 4, 2008). "OPi ou comment construire une biopharma en moins de dix ans - Private Equity Magazine". Private Equity Magazine (in French).
  23. "Assessment report: Zenas" (PDF). EMA CHMP committee. 2009.
  24. "Huxley Acquisition Lands Biomarin New LEMS Treatment". Pharmaceutical Technology. October 28, 2009.
  25. Goldberg, Adrian (November 21, 2010). "Drug firms accused of exploiting loophole for profit". BBC News.
  26. Nicholl DJ, Hilton-Jones D, Palace J, Richmond S, Finlayson S, Winer J, Weir A, Maddison P, Fletcher N, Sussman J, Silver N, Nixon J, Kullmann D, Embleton N, Beeson D, Farrugia ME, Hill M, McDermott C, Llewelyn G, Leonard J, Morris M (2010). "Open letter to prime minister David Cameron and health secretary Andrew Lansley". BMJ. 341: c6466. doi:10.1136/bmj.c6466. PMID 21081599.
  27. Hawkes N, Cohen D (2010). "What makes an orphan drug?". BMJ. 341: c6459. doi:10.1136/bmj.c6459. PMID 21081607.
  28. Keogh M, Sedehizadeh S, Maddison P (2011). "Treatment for Lambert-Eaton myasthenic syndrome". The Cochrane Database of Systematic Reviews (2): CD003279. doi:10.1002/14651858.CD003279.pub3. PMC 7003613. PMID 21328260.
  29. "Evidence Review: Amifampridine phosphate for the treatment of Lambert–Easton Myasthenic Syndrome" (PDF). NHS England. December 2015.
  30. Vedeler, CA; Antoine, JC; Giometto, B; Graus, F; Grisold, W; Hart, IK; Honnorat, J; Sillevis Smitt, PA; Verschuuren, JJ; Voltz, R; Paraneoplastic Neurological Syndrome Euronetwork. (July 2006). "Management of paraneoplastic neurological syndromes: report of an EFNS Task Force". European Journal of Neurology. 13 (7): 682–90. doi:10.1111/j.1468-1331.2006.01266.x. PMID 16834698.
  31. "International Nonproprietary Names for Pharmaceutical Substances (INN) Recommended INN: List 58" (PDF). WHO Drug Information. 21 (3). 2007.
  32. Wahl, Margaret (January 25, 2012). "Jacobus Begins Invitation-Only Trial of 3,4-DAP in LEMS". Muscular Dystrophy Association Quest Magazine Online.
  33. Leuty, Ron (October 31, 2012). "BioMarin licenses North American rights to rare disease drug, invests $5M in Florida company". San Francisco Business Journal.
  34. "Orphan Drug Designations: amifampridine phosphate for congenital myasthenic syndromes". FDA. Retrieved January 14, 2017.
  35. "Orphan Drug Designations: amifampridine phosphate for myasthenia gravis". www.accessdata.fda.gov. FDA. Retrieved January 14, 2017.
  36. Radke, James (October 29, 2014). "Catalyst Using the Expanded Access Program to Conduct Phase IV Study with LEMS Patients". Rare Disease Report. Archived from the original on June 13, 2018. Retrieved June 13, 2018.
  37. "Orrphan designation congenital myasthenic syndromes". FDA. Archived from the original on July 26, 2015.
  38. Burns, TM, et al.I (February 2016). "Editorial by concerned physicians: Unintended effect of the orphan drug act on the potential cost of 3,4-diaminopyridine". Muscle & Nerve. 53 (2): 165–8. doi:10.1002/mus.25009. PMID 26662952.
  39. McEnany, Patrick J. (2017). "A response to a recent editorial by concerned physicians on 3,4-diaminopyridine". Muscle & Nerve. 55 (1): 138. doi:10.1002/mus.25437. ISSN 1097-4598. PMID 27756108.
  40. Tavernise, Sabrina (December 22, 2015). "Patients Fear Spike in Price of Old Drugs". New York Times.
  41. Adams, Ben (April 26, 2016). "Catalyst Pharmaceuticals hit by FDA extra studies request for Firdapse". FierceBiotech.
  42. Adams, Ben (May 17, 2016). "Catalyst to ax 30% of workforce in wake of FDA trial demands". FierceBiotech.
  43. Lima, Debora (March 29, 2018). "Catalyst Pharmaceuticals files new drug application with FDA". South Florida Business Journa.
  44. "Firdapse (amifampridine phosphate) FDA Approval History". Drugs.com. Retrieved February 5, 2019.
  45. "Bernie Sanders asks why drug, once free, now costs $375K". NBC News. Retrieved February 5, 2019.
  46. "Family outraged over life-changing treatment going from free to $375,000 a year". NBC News.
  47. "FDA approves first treatment for children with Lambert–Eaton myasthenic syndrome, a rare autoimmune disorder". fda.gov. Retrieved May 11, 2019.
  48. Drash, Wayne (May 8, 2019). "FDA undercuts $375,000 drug in surprise move". CNN Health. Retrieved May 12, 2019.
  49. "Family outraged over life-changing treatment going from free to $375,000 a year". NBC News.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.