Catalyst Pharmaceuticals

Catalyst Pharmaceutical Partners, Inc.
Public company
Traded as NASDAQ: CPRX
Russell 2000 Component
Industry Biotechnology
Headquarters Coral Gables, FL, United States
Key people
 Patrick J. McEnany, co-founder, chairman, president and chief executive officer
Products in development
Revenue US$ 0 million (2014)[1]
Decrease US$ -15.5 million (2014)[1]
Total assets Increase US$ 43.9 million (2014)[1]
Total equity Increase US$ 35.2 million (2014)[1]
Number of employees
 20 as of March 20, 2015[1]
Website www.catalystpharma.com
Footnotes / references
[2][3]

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", and CPP-115 (a GABA transaminase) for the treatment of infantile spasms.[4][5]

History

Catalyst was founded in 2002, and competed an IPO in 2006.[6] It focused primarily on developing therapies to prevent addiction until 2012.[4]

In 2009, Catalyst in-licensed worldwide rights to a family of GABA inhibitors including CPP-115 from Northwestern University.[7][8] In 2012, it in-licensed patents covering the use of amifampridine phosphate to treat LEMS for the North American market from BioMarin.[9] See below for the history of this drug, before and after Catalyst licensed it..

The company is also developing CPP-115 as a treatment for infantile spasms.[10][11]

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.[12][13][14]

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.[15]

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. Jacobus elected to give the drug away, and did so for about twenty years.[16][17]

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.[18] The hospital licensed the intellectual property on the phosphate form to the French biopharma company OPI, which was acquired by EUSA Pharma in 2007,[19] and the orphan application was transferred to EUSA in 2008.[18] In 2008 EUSA submitted an application for approval to market the phosphate form to the European Medicines Agency under the brand name, Zenas.[20] EUSA, through a vehicle called Huxley Pharmaceuticals, sold the rights to 3,4-DAPP to Biomarin in 2009,[21] the same year that 3,4-DAPP was approved in Europe under the new name Firdapse.[18] BioMarin launched the drug in Europe in April 2010 and through the first nine months of 2012 year had sales of $10.8 million.[22]

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.[23] A group of UK neurologists and pediatricians petitioned to prime minister David Cameron in an open letter to review the situation.[24] 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.[25] 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.[26][27]

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.[20]:5[28] In 2007 the drug's international nonproprietary name was published by the WHO.[29]

In the US, an orphan drug designation for 3,4-DAPP had been granted in 2009[30] and clinical trials were well under way by 2012.[22]

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.[31]

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.[22] Catalyst anticipated that it could earn $300 to $900 million per year in 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.[15] Catalyst went on to obtain a breakthrough therapy designation for 3,4-DAPP in LEMS in 2013,[32] an orphan designation for congenital myasthenic syndromes in 2015[33] and an orphan designation for myasthenia gravis in 2016.[34]

In August 2013, analysts anticipated that FDA approval would be granted to Catalyst in LEMS by 2015.[35]

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 syndromes, causing its stock to rise a bit.[37][38] In April 2015, Jacobus presented clinical trial results with 3,4-DAP at a scientific meeting, causing Catalyst shares to fall by 42%.[17]

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.[15][39] Other commentators noted, however, that Jacobus was not able to meet the needs of all people who could benefit from the drug via its free program, and that its manufacturing practices had quality control problems, with 483 FDA citations in 2011 and 2012.[16] Similarly, at the urging of Assistance Publique-Hôpitaux de Paris, the French drug authority had reviewed the use of the free base in light of the manufactured phosphate form in 2006, and had urged doctors in France not to use the free base form due to quality issues.[40]

In December 2015 Catalyst submitted its new drug application to the FDA,[41] 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.[42][12] Catalyst cut 30% of its workforce to save money to conduct the trials.[43] In March 2018 the company re-submitted its NDA.[44]

References

  1. 1 2 3 4 5 "Catalyst Pharmaceuticals 2014 Annual Report Form (10-K)" (XBRL. Retrieved 2015-03-05). United States Securities and Exchange Commission.
  2. ↑ Catalyst Pharmaceuticals (CPRX) stock information via Wikinvest.
  3. ↑ Catalyst Pharmaceuticals (CPRX) annual SEC balance sheet filing via Wikinvest.
  4. 1 2 Mann Jr., Joseph A. (18 July 2015). "The big gamble: Catalyst Pharmaceuticals of Coral Gables bets on new drug for rare disease". Miami Herald.
  5. ↑ Nehamas, Nicholas. “Catalyst Pharmaceuticals reports second-quarter net loss, plans to submit new drug for FDA approval”, “Miami Herald”, 11 August 2015. Retrieved on 26 August 2015.
  6. ↑ "Catalyst Pharmaceuticals Registration Statement Form S-1" (XBRL. Retrieved 2015-09-08). United States Securities and Exchange Commission.
  7. ↑ Hawker D. and R. Silverman. “Synthesis and evaluation of novel heteroaromatic substrates of GABA Aminotransferase”, Bioorganic & Medicinal Chemistry, 1 October 2012. Retrieved on 8 September 2015.
  8. ↑ Brian Bandell. “Catalyst Pharmaceutical signs licensing deal with Northwestern” “South Florida Business Journal”, 31 August 2009. Retrieved on 8 September 2015.
  9. ↑ “Catalyst Acquires Late-Stage Orphan Drug from BioMarin, “Genetic Engineering and Biotechnology News, 1 November 2012. Retrieved on August 27, 2015.
  10. ↑ Briggs SW, et al. “CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of infantile spasms”, Epilepsia. January 2014. Retrieved on 8 September 2015.
  11. ↑ “Orphan Drug Designations and Approvals”, US Food and Drug Administration, 15 September 2015. Retrieved on 8 September 2015.
  12. 1 2 Tavernise, Sabrina (February 17, 2016). "F.D.A. Deals Setback to Catalyst in Race for Drug Approval". New York Times.
  13. ↑ 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.
  14. ↑ Lowe, Derek (21 October 2013). "Catalyst Pharmaceuticals And Their Business Plan". In the Pipeline.
  15. 1 2 3 Deak, Dalia (February 22, 2016). "Jacobus and Catalyst Continue to Race for Approval of LEMS Drug". Bill of Health.
  16. 1 2 Silverman, Ed (5 April 2016). "A family-run drug maker tries to stay afloat in the Shkreli era". STAT News.
  17. 1 2 "Jacobus Pharmaceuticals". Drug R&D Insight. April 25, 2015.
  18. 1 2 3 "Public summary of opinion on orphan designation" (PDF). EMA. 14 June 2010.
  19. ↑ 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).
  20. 1 2 "Assessment report: Zenas" (PDF). EMA CHMP committee. 2009.
  21. ↑ "Huxley Acquisition Lands Biomarin New LEMS Treatment". Pharmaceutical Technology. October 28, 2009.
  22. 1 2 3 Leuty, Ron (October 31, 2012). "BioMarin licenses North American rights to rare disease drug, invests $5M in Florida company". San Francisco Business Journal.
  23. ↑ Goldberg, Adrian (21 November 2010). "Drug firms accused of exploiting loophole for profit". BBC News.
  24. ↑ 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.
  25. ↑ Hawkes N, Cohen D (2010). "What makes an orphan drug?". BMJ. 341: c6459. doi:10.1136/bmj.c6459. PMID 21081607.
  26. ↑ 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. PMID 21328260.
  27. ↑ "Evidence Review: Amifampridine phosphate for the treatment of Lambert–Easton Myasthenic Syndrome" (PDF). NHS England. December 2015.
  28. ↑ 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.
  29. ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN) Recommended INN: List 58" (PDF). WHO Drug Information. 21 (3). 2007.
  30. ↑ "Orphan Drug Designations for amifampridine phosphate for LAMS". www.accessdata.fda.gov. FDA. Retrieved 14 January 2017.
  31. ↑ Wahl, Margaret (January 25, 2012). "Jacobus Begins Invitation-Only Trial of 3,4-DAP in LEMS". Muscular Dystrophy Association Quest Magazine Online.
  32. ↑ Baker DE (Nov 2013). "Breakthrough Drug Approval Process and Postmarketing ADR Reporting". Hospital Pharmacy. 48 (10): 796–8. doi:10.1310/hpj4810-796. PMC 3859287. PMID 24421428.
  33. ↑ "Orphan Drug Designations: amifampridine phosphate for congenital myasthenic syndromes". FDA. Retrieved 14 January 2017.
  34. ↑ "Orphan Drug Designations: amifampridine phosphate for myasthenia gravis". www.accessdata.fda.gov. FDA. Retrieved 14 January 2017.
  35. ↑ Bandell B (August 28, 2013). "Shares of Catalyst Pharmaceuticals soar 42% on FDA news". South Florida Business Journal.
  36. ↑ Radke, James (October 29, 2014). "Catalyst Using the Expanded Access Program to Conduct Phase IV Study with LEMS Patients". Rare Disease Report.
  37. ↑ "Orrphan designation congenital myasthenic syndromes". FDA. Archived from the original on July 26, 2015.
  38. ↑ Ampel, Celia (5 March 2015). "Catalyst Pharma stock rises 5% after firm hits FDA milestone". South Florida Business Journal.
  39. ↑ 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.
  40. ↑ "Point d'information sur l'utilisation de la 3.4 diaminopyridine". ANSM : Agence nationale de sécurité du médicament et des produits de santé. December 18, 2006.
  41. ↑ Tavernise, Sabrina (December 22, 2015). "Patients Fear Spike in Price of Old Drugs". New York Times.
  42. ↑ Adams, Ben (April 26, 2016). "Catalyst Pharmaceuticals hit by FDA extra studies request for Firdapse". FierceBiotech.
  43. ↑ Adams, Ben (May 17, 2016). "Catalyst to ax 30% of workforce in wake of FDA trial demands". FierceBiotech.
  44. ↑ Lima, Debora (March 29, 2018). "Catalyst Pharmaceuticals files new drug application with FDA". South Florida Business Journa.
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